The novel digital therapeutic Axia improves disease activity, functionality, and quality of life in axial spondyloarthritis patients: a randomized controlled trial

The novel digital therapeutic Axia improves disease activity, functionality, and quality of life in axial spondyloarthritis patients: a randomized controlled trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article The novel digital therapeutic Axia improves disease activity, functionality, and quality of life in axial spondyloarthritis patients: a randomized controlled trial Patrick-Pascal Strunz, Matthias Froehlich, Tobias Heusinger, Maxime Le Maire, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7526871/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Despite increasing digitalization and the central role of non-pharmacological interventions in rheumatic diseases, no digital therapeutic (DTx) has yet been shown to meaningfully improve disease activity in rheumatology. Axia is a novel app-based DTx for axial spondyloarthritis (axSpA) that combines personalized exercise therapy, patient education, and disease management, supported by gamification elements to enhance long-term adherence. To evaluate its clinical efficacy, we conducted a 12-week nationwide, randomized, controlled interventional trial (RCT) involving 200 axSpA patients with stable pharmacotherapy. Patients were randomized (1:1) to either using Axia (intervention group) or standard of care (control group). Of the 200 axSpA patients enrolled, 186 participants (95 in the intervention group and 91 in the control group) completed the study. Compared to control, participants in the Axia intervention group demonstrated significant improvements in disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]; ANCOVA-estimated group difference: -1.508, p<0.001), functional status (Bath Ankylosing Spondylitis Functional Index [BASFI]; -1.139; p<0.001) and disease-specific quality of life (Ankylosing Spondylitis Quality of Life questionnaire [ASQoL]; -2.297; p<0.001), all exceeding minimal clinically important difference (MCID) thresholds. Furthermore, a significantly higher proportion of patients in the intervention group achieved an Assessment of Spondyloarthritis International Society (ASAS)20 response compared to the control group (51% vs. 9%; p<0.001), and the ASAS40 response rate was also markedly higher (23% vs. 3%; p<0.001). No concerning safety signals were observed. These findings mark the first large-scale RCT to demonstrate that a digital intervention can improve disease activity in inflammatory rheumatic disease, supporting its potential as a scalable, non-pharmacological care model. DRKS-ID: DRKS00033783 Health sciences/Medical research/Clinical trial design/Randomized controlled trials Health sciences/Health care/Therapeutics Figures Figure 1 Figure 2 Figure 3 Main Non-pharmacological interventions such as physical activity and patient education are a cornerstone in the management of axial spondyloarthritis (axSpA), an inflammatory rheumatic and musculoskeletal disease (iRMD) characterized by chronic inflammation of the axial skeleton [1]. In particular, home-based exercise (HbE) has been shown to improve disease activity, physical function and quality of life [2], and is thus strongly recommended in national and international guidelines [3-5]. However, the effective translation of these recommendations in real-world clinical practice remains a major challenge, as a considerable proportion of patients underutilize or fail to adhere to such measures, particularly exercise therapy [6]. This lack of sustained engagement has far-reaching consequences, as patients who do not engage in regular exercise interventions are more likely to experience progressive functional and mobility limitations, higher disease activity, and poorer disease-related quality of life [7]. Digital therapeutics (DTx) may offer a scalable solution to this gap by delivering structured, individualized interventions directly to patients in their everyday environments [8, 9]. In doing so, DTx may reduce key barriers to adherence, including limited access to physiotherapy, time constraints, and motivational challenges [10, 11]. Despite growing interest and development efforts, however, no DTx in rheumatology has yet demonstrated clinically meaningful improvements in disease activity in a large-scale randomized controlled trial (RCT) [9]. This evidentiary gap currently limits their integration into standard care pathways. To address these gaps, the DTx Axia was developed by a start-up of two medical students in collaboration with the University Hospital of Wuerzburg, and the German axSpA patient self-help association [12]. Axia is designed to provide axSpA-specific HbE and structured patient education, complemented by additional disease self-management tools. Gamification elements are integrated to enhance engagement and maximize adherence to therapy [12]. To prove Axia’s efficacy, we conducted the Bechterew-App Trial, a three-phase randomized controlled trial (RCT) involving 200 axSpA patients with stable pharmacotherapy (German registry of clinical trials (DRKS), DRKS-ID: DRKS00033783). To our knowledge, this represents the first large-scale RCT in rheumatology to demonstrate that a DTx can produce clinically meaningful improvements in disease activity, function and disease-specific quality of life, thereby providing a robust evidence base that may facilitate the future integration of DTx into standard rheumatology care. Results Recruitment and Baseline Characteristics Participants were recruited nationwide in Germany between March 2024 and December 2024 with the support of patient self-help associations, social media, and rheumatology practices. Of 453 individuals screened for eligibility, 200 were enrolled and randomized 1:1 to receive either Axia or standard of care for 12 weeks. The primary outcome assessment was conducted at week 12 and completed by 186 participants. The main reason for discontinuation was withdrawal of informed consent; one participant was lost to follow-up (Fig. 1). Baseline characteristics for the intention-to-treat population (n=187) are shown in Table 1. Apart from a slightly higher proportion of female participants in the intervention group, no relevant differences were observed. Age, use of biological (b)DMARDs or targeted synthetic (ts)DMARDs, physiotherapy, and exercise behavior were well balanced between groups. Primary Outcomes After 12 weeks, participants in the Axia intervention group showed significantly greater improvements in disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]; ANCOVA-estimated group difference: -1.508; 95% Confidence Interval (CI): -1.874 to -1.142; p<0.001), functional status (Bath Ankylosing Spondylitis Functional Index [BASFI]; -1.139; 95% CI: -1.524 to -0.755; p<0.001) and disease-specific quality of life (Ankylosing Spondylitis Quality of Life questionnaire [ASQoL]; -2.297; 95% CI: -2.983 to -1.610; p<0.001) (Fig. 2). All effects exceeded their respective minimal clinically important difference (MCID) thresholds. Effect sizes were large across all primary outcomes, with Cohen’s d values of 1.20 for disease activity, 0.87 for functional status, and 0.97 for quality of life. Participants were instructed to remain on stable anti-rheumatic pharmacotherapy during the trial to minimize the potential influence of treatment changes. Nevertheless, some treatment switches occurred. To assess their impact, the primary outcomes of the per-protocol (PP) population were compared to the intention-to-treat (ITT) population. Effect estimates in the PP population were numerically higher and consistent in direction with the ITT analysis, indicating that protocol deviations, including treatment modifications, had no substantial impact on the results (Table 2). Robustness of the findings was further evaluated through additional ANCOVA analyses adjusting for sex. No significant influence was observed, and treatment effects remained virtually unchanged, suggesting that the slight imbalance in sex distribution did not materially influence the outcomes (Table 2). Secondary Outcomes Secondary outcomes included response rates according to the Assessment of Spondyloarthritis International Society (ASAS)20 and ASAS40 criteria, as well as changes in global pain, patient global assessment (PtGA), self-efficacy, health literacy. After 12 weeks of app use, significantly more participants in the intervention group met the ASAS20 (51% vs. 9%; p<0.001) and ASAS40 (23% vs. 3%; p<0.001) response criteria compared to the control group (Fig. 3). Adjusted ANCOVA models showed significant group differences in favor of the intervention for global pain, PtGA, self-efficacy, and exercise adherence. No significant difference was observed for health literacy (Fig. 3). Adherence rates In addition to self-reported adherence, participants’ usage of Axia was objectively tracked: During the 12-week-period, the app was used on an average of 69 days (SD 18.3), and cumulatively, for an average of 1145 mins (SD 937.6 mins). A total of 77.9% of participants used the app on at least five days a week, and 29.7% used Axia daily. On at least half of the days, the app was used by 93% of participants. 98.9% of the participants of the intervention group stated that they would like to continue using Axia. Safety All adverse events (AE) were assessed during the trial. In total, 55 AEs (29%) were observed, 4 of which were severe AEs (SAE). AE incidence rates of the intervention group (22%, n=21; 1% SAE, n=1) were lower than in the control group (37%, n=34; 3% SAE, n=3). No device-related AEs were identified in the intervention group. Table 3 lists all observed AEs. Discussion This RCT provides the first robust evidence that a DTx can achieve clinically meaningful improvements in disease activity, functional status, and quality of life in axSpA patients receiving stable pharmacotherapy. The Bechterew-App Trial met all three primary endpoints, demonstrating that Axia - an app-based, multimodal intervention integrating exercise therapy, patient education, and self-management support - may serve as a scalable, non-pharmacological treatment modality for axSpA. To our knowledge, this is the first large-scale, methodologically rigorous RCT to show that a DTx can significantly reduce disease activity in an iRMD. The efficacy observed with Axia represents a marked advance over previous digital health studies in rheumatology. The positive effects of non-pharmacological therapies for axSpA are well-established, mostly from interventions delivered in traditional formats such as printed manuals or booklets [2, 13, 14]. In recent years, several DTx-supported interventions have been explored [15, 16]. However, these studies have often suffered from methodological limitations, including small sample sizes, non-disease-specific applications, or insufficient control designs. Crucially, none of these DTx achieved significant or clinically relevant improvements in key outcomes such as disease activity, functional status or quality of life [15, 16]. In contrast, the Bechterew-App Trial provides high-quality evidence that a DTx, specifically tailored to axSpA, can achieve such outcomes. The magnitude of the treatment effects observed in this trial is clinically noteworthy. The ASAS20 and ASAS40 response criteria are commonly used as primary or secondary endpoints in pharmacological trials for axSpA [17-20]. Historically, exercise interventions have shown only modest effects on disease activity [21], and consequently, robust data on their impact on ASAS20 or ASAS40 responses are lacking. In this trial, the intervention group achieved ASAS20 and ASAS40 response rates of 51% and 23%, respectively, compared with 9% and 3% in the control group. For context, trials with tumor necrosis factor inhibitors (TNFi) typically report ASAS20 response rates of around 65% and ASAS40 rates between 39% and 48% [22]. A meta-analysis by Betts et al. found ASAS20 responses ranging from 50.5% to 71.7% for TNFi and interleukin-17 inhibitors, with placebo groups achieving around 27.9% for ASAS20 and 13.5% for ASAS40 [23]. While these figures offer a useful benchmark, differences in study design, blinding, and patient selection inevitably preclude direct head-to-head comparison and caution against interpreting the present results as evidence of equal or comparable efficacy to pharmacological treatments. Nevertheless, the magnitude of the ASAS20 and ASAS40 responses underscores the high therapeutic potential of Axia, and - more broadly - of DTx approaches in iRMDs. The pronounced efficacy of Axia may be attributable to its low-threshold, location-independent accessibility as well as its multimodal, gamified design, which integrates physical activity, patient education, and behavioral support within a single digital platform. In addition, unlike generic exercise applications, Axia was developed exclusively for axSpA, integrating targeted exercise therapy tailored to the pathophysiology and movement limitations of this condition [12]. Another factor that may explain its superior effectiveness compared with conventional home-based exercise approaches is the holistic physical activity concept deployed in this trial. The DTx provides patients with a variety of options to increase physical activity, including patient-tailored axSpA-specific HbE of varying durations, cardiovascular-focused training sessions, targeted HbE-modules for acute pain and morning stiffness, as well as direct promotion of sports participation alongside general activity enhancement through features such as daily step goals, a built-in step counter, and smartwatch integration [12]. Additionally, Axia especially encourages the integration of brief, highly accessible exercise habits into daily routines, such as linking one or two short exercises with a daily routine like getting out of bed or brewing coffee [12]. This contrasts with many other exercise DTx that focus primarily on longer, fixed sessions (e.g., 20 minutes in the evening) [15, 16]. Combining a wide range of exercise options and encouraging short, distributed bouts of activity embedded into everyday life may therefore represent a promising approach for exercise-based DTx in iRMDs and other chronic diseases. Sustaining long-term adherence is a recognized challenge in both exercise interventions and DTx, with low engagement and high attrition frequently cited as key barriers to efficacy [24, 25]. As personal communication is known to enhance adherence to DTx by motivating the user [25], the Bechterew-App Trial was deliberately designed to simulate real-world conditions by avoiding such interactions and to minimize potential adherence bias. After enrollment, interaction was limited to baseline allocation and post-assessment follow-up, with no motivational prompts. Accordingly, no proactive contact was initiated with study participants during this period and only channels for participant inquiries were made available. With a total of 77.9% of participants using the DTx on at least five days a week over a 12-week-period, Axia still achieved adherence and usage rates far exceeding those reported in other axSpA DTx trials in real-world settings [24, 25]. Gamification features - such as daily activity streaks, milestone tracking, and point rewards - may have contributed to sustained engagement and the observed treatment effects. Moreover, the possibility of perceiving early improvements in pain and mobility could have created a reinforcing feedback loop that further encouraged continued use. However, it remains uncertain whether such high adherence rates observed under trial conditions can be maintained in routine clinical practice, where external accountability and structured follow-up are often absent. Further pragmatic and longitudinal studies are needed to determine whether the observed engagement and clinical benefits are sustainable. Long-term follow-up studies of the Bechterew-App Trial are currently underway to address these questions. The findings of this trial also have relevance beyond axSpA. In Germany, Axia has been submitted for approval as a reimbursable digital health application (DiGA) under the national fast-track pathway for prescription DTx. If approved, Axia could be made available to all eligible patients nationwide, providing a scalable, low-barrier treatment option that complements existing pharmacological and non-pharmacological therapies [26]. Planned translations into additional languages and implementation in other European countries as well as the United States may also enable broader access to structured, evidence-based exercise therapy for axSpA in health systems where such programs are limited or inconsistently provided. The underlying therapeutic approach - disease-specific, adaptive exercise combined with patient education, behavioral support, and gamification elements - represents a framework that could be adapted for other iRMDs in which exercise and self-management are integral to care but long-term adherence is suboptimal. Regarding safety, no concerning safety signals were observed, especially no device-related AEs. The main limitation of this study is the absence of a double-blinded design and a placebo group. This is a common challenge in RCTs involving DTx, as participants can often easily unblind themselves by reviewing the internet on the content and function of the verum app. Blinding of the study personnel was also not implemented; however, as per protocol, no direct contact occurred after group allocation, and all questionnaires were self-reported and completed by participants at home via electronic case report forms (eCRFs), minimizing the potential for investigator-induced bias. A further limitation is the exclusive reliance on patient-reported outcome measures (PROMs) without objective clinical or biomarker-based endpoints. While the remote design and nationwide recruitment precluded on-site assessments in the Bechterew-App Trial, future studies should integrate objective endpoints where feasible. In a small number of cases (five participants in the intervention group and eight participants in the control group), baseline data had to be deleted in accordance with data protection regulations, as consent to participate in the study was withdrawn. While this is a limitation, all withdrawals occurred prior to the 12-week assessment, and the small number of cases reduces the likelihood of systematic bias. Key strengths of this trial include the large sample size and the high proportion of complete datasets, both of which enhance statistical power and minimize attrition bias. Moreover, the demographic and treatment characteristics of the study population - including the frequency of bDMARD and NSAID use, physiotherapy treatment, and levels of HbE and other sports activities - were closely aligned with those reported in recent national real-world observational studies [27, 28], supporting representativeness. The higher mean BASDAI in our trial (5.17 vs. 3.9 in the ATTENTUS study [28]) reflects the inclusion criterion of BASDAI ≥ 3.5, which was applied to reduce heterogeneity and ensured that treatment effects were evaluated in patients with at least moderate disease activity. Women were overrepresented, likely reflecting the higher uptake of digital health applications among women, who account for approximately 73% of DHA users according to national health insurance data [29]. Another strength is the low-threshold participation enabled by the remote design, which facilitated inclusion of patients from across Germany without on-site visits. In conclusion, the Bechterew-App Trial provides the first large-scale, methodologically rigorous evidence that a disease-specific, app-based multimodal intervention can achieve significant and clinically meaningful improvements in disease activity, functional status, and quality of life in axSpA patients receiving stable pharmacotherapy. These findings support the potential of Axia to complement existing pharmacological and non-pharmacological treatments and help close the gap between guideline-based exercise recommendations and their limited implementation in routine care. While the absence of blinding, reliance on PROMs, and the short intervention period warrant cautious interpretation, the magnitude of the observed effects and high adherence rates under real-world-like conditions justify further pragmatic and long-term evaluations. The Axia approach could also serve as a model for other iRMDs, where structured exercise and self-management are central to care but long-term adherence remains a challenge. Declarations Data availability The data underlying the results of this clinical trial are included in the article and its supplementary materials. To protect participant confidentiality and proprietary content, deidentified individual-level data are available upon reasonable request and subject to restricted access. Requests should be directed to the corresponding author P.-P. Strunz and must include a brief research proposal specifying the intended use. Code availability The use of a custom code is not applicable in this paper. Acknowledgments The abstract of this study was presented as oral presentation at the EULAR congress 2025 in Barcelona (LB0002). We would like to thank all the patients who participated in the trial. Furthermore, we also would like to thank the German patient self-help association (DVMB) for supporting us. We are also grateful to our statisticians Dr. Victoria Rücker and Dr. Uwe Malzahn for performing the sample size calculation. Applimeda is the developer and rights holder of Axia. M.lM., T.H., and R.L. are shareholders, partners, or employees of Applimeda. All other authors are not financially dependent on Applimeda. Author contributions Conceptualization: P.-P.S., M.F., T.H., M.lM., M.S. Methodology: P.-P.S., M.F., T.H., M.lM., M.S., A.F., K.S.L., H.L., A.S., B.S. Investigation: P.-P.S., M.F., T.H., M.lM., M.S., P.Po., O.G. Formal Analysis: P.-P.S., M.F., T.H., M.lM., M.S., P.Po. Writing – Original Draft: P.-P.S., M.F., T.H., M.lM., M.S. Writing – Review & Editing: P.-P.S., M.F., T.H., M.lM., A.F., K.S.L., P.Po., M.G., H.L., O.G., R.L., A.S., L.H., B.S., H.E., M.S. All authors reviewed and approved the final manuscript. Competing interests P.-P.S. received speaker’s fees and travel grants from Janssen-Cilag, Galapagos, Eli Lilly, Boehringer/Ingelheim and AbbVie (less than US$10,000 each) as well as research funding from Chugai (US$25,000), Novartis (US$150,000) and AbbVie (US$ 12,000). M.lM. reported to be Chief Executive Officer of Applimeda, Co-Founder and shareholder of Applimeda GmbH. T.H. reported to be Chief Regulatory & Medical Officer of Applimeda, Co-Founder and shareholder of Applimeda GmbH. J.K. stated to be PRRC of Applimeda. H.L. received travel grants from UCB, Boehringer Ingelheim, Pfizer and AbbVie as well as compensation for consulting activity from Pfizer and for lecturing activities from Janssen. A.F., K.S.L., P.Po., O.G., H.E., and A.S. declared no conflict of interest. M.G. received travel grants, compensation for advisory boards or speaker’s fees from AbbVie, Chugai, Eli Lilly, Hexal, Janssen, Novartis, Pfizer and Takeda and research funding from Novartis (US$150,000) . R.L. declared to be Chief Technology Officer of Applimeda, Co-Founder and shareholder of Applimeda GmbH. L.H. declared to be Former Chief Executive Officer of DVMB. E.S. declared to be Chief Executive Officer of DVMB. B.S. declared no conflict of interest. M.F. received speaker’s fees, travel grants or compensation for board memberships from AbbVie, Novartis, Janssen and Eli Lilly. M.S. received speaker’s fees, travel grants, research funding or compensation for consultancies or board memberships from AbbVie, Actelion, AstraZeneca, BMS, Boehringer/Ingelheim, Celgene, Chugai/Roche, Eli Lilly, Genzyme, Gilead, Hexal/Sandoz, Janssen-Cilag, MSD, Novartis, Pfizer, Sanofi Pasteur, Takeda (Shire) and UCB (less than US$10,000 each) and research funding from Novartis (US$150,000). References Sieper, J., Braun, J., Dougados, M. & Baeten, D. Axial spondyloarthritis. Nat. Rev. Dis. 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Digital health applications from a government-regulated directory of reimbursable health apps in Germany: a systematic review for evidence and bias. Mhealth 9, 35 (2023). https://doi.org/10.21037/mhealth-23-17 Albrecht, K. et al. Current data on rheumatological care: annual report from the National database (NDB) of the regional collaborative arthritis centres in Germany. Z. Rheumatol. 83, 666–674 (2024). https://doi.org/10.1007/s00393-024-01497-9 Meyer-Olson, D., Hoeper, K., Hammel, L., Lieb, S., Haehle, A. & Kiltz, U. Nonpharmacological treatment measures, rehabilitation services and membership in patient support groups in axial spondylarthritis (The ATTENTUS axSpA study). Z. Rheumatol. 83, 500–509 (2024). https://doi.org/10.1007/s00393-023-01410-w GKV Spitzenverband. DiGA-Bericht 2025. https://www.gkv-spitzenverband.de/media/dokumente/krankenversicherung_1/telematik/digitales/2024_DiGA-Bericht_final.pdf (2025). Pavy, S., Brophy, S. & Calin, A. Establishment of the minimum clinically important difference for the Bath Ankylosing Spondylitis indices: a prospective study. J. Rheumatol. 32, 80–85 (2005). Haywood, K.L., Garratt, A.M., Jordan, K., Dziedzic, K. & Dawes, P.T. Disease-specific, patient-assessed measures of health outcome in ankylosing spondylitis: reliability, validity and responsiveness. Rheumatology (Oxford) 41, 1295–1303 (2002). https://doi.org/10.1093/rheumatology/41.11.1295 Methods Study design The Bechterew-App Trial was designed as a monocentric, prospective, randomized controlled interventional trial to evaluate the efficacy of the DTx Axia in axSpA patients receiving stable pharmacotherapy. Following baseline assessment, participants were randomized in a 1:1 ratio to either the intervention or control group. Randomization was stratified based on whether participants were receiving weekly individual physiotherapy sessions (yes/no). Participants in the intervention group received access to Axia for a 12-week period in addition to standard of care. The control group received standard of care alone, including pharmacological and non-pharmacological treatment as recommended by their treating physicians. Neither participants nor investigators were blinded. The study was conducted as a German nationwide remote study led by the University hospital of Wuerzburg, Germany. The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. The study protocol was approved by the ethics committee of the medical faculty of the University of Wuerzburg, Wuerzburg (DE/EKBY13) (Date July 31st, 2023, No 92/23-am). The trial was prospectively registered at the German Clinical Trials Register (DRKS), DRKS-ID: DRKS00033783), date of first registry March, 1 st , 2024. Participants Candidates were eligible for participation in the Bechterew-App Trial if they met all of the following inclusion criteria: Age ≥ 18 years Signed informed consent Confirmed diagnosis of axSpA by an official medical document issued by a physician BASDAI score ≥ 3.5 at screening Stable pharmacotherapy regarding axSpA for at least 8 weeks prior to screening, with no planned therapy changes Only moderate physical activity, defined as: no more than one physiotherapy session per week on average in the last three months; no more than a total of 90 minutes of sports activities per week with sports activities carried out on no more than three days per week; and no more than a total of 50 minutes of axSpA-specific HbE per week on with axSpA-specific HbE done on no more than four days per week. Sufficient smartphone proficiency, defined as regular and independent use of any smartphone app in the past Ownership of a personal Android or iOS-compatible smartphone with mobile internet access, meeting the technical requirements to use Axia Sufficient language skills to independently complete self-reported questionnaires Candidates were excluded if they met any one of the following criteria: Pregnancy Any state or disorder (i.e. acute myocardial infarction) not allowing regular exercise performance Any state or disorder for which regular exercise is a contraindication Any contraindication for Axia usage according to the official instructions of use Active use of another smartphone-based application for axSpA therapy Candidate participants were informed about the study via various publicly accessible media (e.g. print and online media, social media or flyers). The recruitment process was supported by rheumatology practices and the German Association for Bechterew's Disease (DVMB), a nationwide self-help organisation for people with axSpA, as well as their partners. Interested patients could register at the public available study homepage (https://studie-bechterew.de) to receive the study documents for screening including the screening questionnaire and the informed consent form. Candidates then had to send the completed study documents along with a medical report confirming the diagnosis of axSpA. After reviewing the study documents, suitable candidates for the trial received a phone call from an investigator physician to verify eligibility and to obtain informed consent. Eligible participants were enrolled in the trial and invited by email to complete the baseline questionnaire via the eCRF Magana Trial Manager by MaganaMed GmbH (https://maganamed.com). Intervention The intervention consisted of using the smartphone application Axia over a 12-week period. Axia is a German-language, disease-specific, and patient-tailored DTx developed for individuals with axSpA. The app includes a library of over 250 exercises, delivered via an adaptive algorithm that continuously adjusts the therapeutic program to the patient’s individual needs. Specific modules address acute pain and morning stiffness. In addition, Axia promotes the integration of short, daily exercise routines into everyday life, encourages users to engage in sports activity and maintain an overall active lifestyle, including step-based activity goals with smartwatch compatibility. Beyond exercise therapy, Axia features a digital patient academy with structured educational content and tools for disease self-management. All components are embedded in a gamified app environment designed to enhance motivation and support long-term adherence. Axia is a Conformité Européenne (CE) class I medical device certified under the European Medical Device Regulation (MDR). Axia and its functions have already been described in detail elsewhere [12]. Primary and secondary endpoints and their assessment The primary endpoints were changes in disease activity (measured by BASDAI), disease-specific functionality (assessed by BASFI), and axSpA-specific quality of life (assessed by ASQoL) after 12 weeks, comparing the intervention group with the control group. All three instruments are standard patient-reported outcome measures (PROM) routinely used in axSpA care and pharmacological trials. Literature-based minimal clinically important differences (MCIDs), pre-defined in the study protocol, were as follows: a reduction of ≥1.0 point or ≥22.5% in BASDAI, ≥0.7 points or ≥17.5% in BASFI CITATION Pav \l 1031 [30] , and ≥1.8 points in ASQoL (equivalent to 10% of the total scale range) CITATION Hay \l 1031 [31] . As patients are familiar with answering these questionnaires in clinical routine, no specific training was required. All PROMs were digitalized within the eCRF and completed independently by participants at home, without access to previous responses or interaction with study personnel. Baseline and week-12 assessments were made available via email invitations. To simulate real-world conditions, no financial compensation or additional incentives were provided. Secondary endpoints included self-efficacy (ASKU), health literacy assessed (German version of the 16‑Item European Health Literacy Survey Questionnaire [HLS-EU Q16]), global pain (numeric rating scale [NRS]), patient global assessment of disease activity (PtGA), and self-reported adherence to exercise therapy (Exercise Adherence Rating Scale[(EARS]). All secondary measures were collected via eCRF at baseline and week 12. In addition, ASAS20 and ASAS40 response rates were calculated. ASAS20 response was defined as an improvement of at least 20% and at least 1 unit (on a 0-10 scale) from baseline in three of four domains (spinal pain [BASDAI question 2], spinal inflammation [mean of BASDAI questions 5 and 6], physical function [BASFI], and patient global assessment [PtGA]), with no worsening in the remaining domain (defined as a deterioration of ≥20% or ≥1 unit). ASAS40 response required an improvement of at least 40% and 2 units in three of the four domains without any worsening in the fourth. At week 12, participants were also asked via open-ended questions about adverse events and their willingness to continue with Axia. Sample size calculation Sample size calculation was performed by the Clinical Trial Center at the University Hospital Würzburg (ZKSW). The trial included three primary endpoints - changes in ASQoL, BASDAI, and BASFI from baseline to week 12. To control for type I error due to multiple testing, the overall significance level (α = 0.05) was conservatively adjusted using Bonferroni correction, resulting in a per-test alpha of 0.0167. An ANCOVA model adjusted for baseline values was pre-specified as the primary analysis method to compare intervention and control group. Means and standard deviations were derived from prior studies with comparable interventions [2] [13]. Multiple scenarios were considered in calculation based on different correlation assumptions with ρ varying from 0.3 to 0.7 between baseline and follow-up. ASQoL was identified as the most limiting endpoint in terms of required sample size. Assuming a conservative correlation of ρ = 0.4, a total of 160 participants (80 per group) was calculated to achieve 90% power. Dropout-rate was estimated to be 20%. To account for this, an additional 20% were added to the 160 participants resulting in a total sample size of 200 participants (100 per group). Randomization The randomization method was stratified block randomization (ratio 1:1) in randomly defined blocks of 4 or 6. The stratification factor was physiotherapy (Regular physiotherapy prior to the study vs. no regular physiotherapy prior to the study). Separate randomization lists were generated by the ZKSW for each stratum and implemented in a secure allocation software. The study team was blinded to the allocation sequence, and group assignment was revealed only after eligibility confirmation and entry of participant data into the system. Statistical analysis The primary analyzed population was the ITT population. Missing values were replaced using an copy increments in reference approach. The statistical analysis was carried out by the ZKSW and BioStats GmbH. Primary and secondary outcomes were analyzed by ANCOVA models, adjusted for the respective baseline value, comparing the intervention and control groups after 12 weeks. Due to the slightly higher proportion of women in the intervention group compared to the control group, additional ANCOVA adjustments were made for sex besides adjustment for baseline values. Descriptive statistics, including mean, standard deviation, and minimum/maximum values, were used to summarize baseline characteristics. All mandatory pretests were performed before the ANCOVA was carried out: The residuals were tested for normal distribution, the Breusch-Pagan test and the White-test were used to analyze homoscedasticity, and the regression slopes were tested for homogeneity. If no systematic deviations were found in the graphical residual analysis, ANCOVA was used as the primary analysis method. To address multiple testing and accumulation of alpha errors, the Benjamini-Hochberg method was used to adjust the significance level. The primary endpoint was considered achieved if the statistical analysis using the baseline adjusted ANCOVA described above together with the Benjamini-Hochberg adjustment showed a statistically significant improvement (p<0.05). Differences in ASAS20 and ASAS40 response rates between intervention and control group were analyzed by Chi-Suare-test. For all analyses, Prism and R were used. The statistical analysis plan is available as part of the study protocol in the German registry of clinical trials (DRKS-ID: DRKS00033783). Tables Table 1 : Baseline characteristics Intervention (n=95) Control (n=92) Mean age; years (SD) 50 (12) 51 (11) BASDAI; absolute (SD) 5.32 (1.31) 5.02 (1.26) Female Proportion; % (n) 74% (70) 59% (54) NSAIDs; % (n) 55% (52) 62% (57) bDMARD or tsDMARD usage; % (n) 56.3% (53) 60.2% (55) Physical Therapy Professional Physiotherapy Once per week; % (n) 56% (53) 60% (55) No Physiotherapy; % (n) 44% (42) 40% (37) Other forms of exercise and physical therapy Home-based Exercise; % (n) 39% (37) 41% (38) Functional training; % (n) 31% (29) 34% (31) Other Sports; % (n) 32% (30) 34% (31) Table 2 : Comparison of ITT and PP analysis Intention-to-treat (ITT) Analysis Per-protocol (PP) Analysis Intervention n=95 Control n=92 p-value ² Intervention n=88 Control n=73 p-value ² Delta BASDAI (SD) -1.66 (1.41) -0.11 (1.15) <0.001 - 1.76 (1.39) -0.11 (1.15) <0.001 Delta BASFI (SD) -1.12 (1.40) 0.06 (1.31) <0.001 -1.24 (1.37) 0.11 (1.38) <0.001 Delta ASQoL (SD) -2.51 (2.55) -0.16 (2.26) <0.001 -2.65 (2.52) -0.21 (2.21) <0.001 Table 3 : Safety during the 12-week treatment period Adverse Events (AEs) Control group (n=92) Intervention group (n=95) Total (n=187) Any adverse event 34 (37%) 21 (22%) 55 (29%) Flare 7 (8%) 9 (10%) 16 (9%) Uveitis 0 (0%) 1 (1%) 1 (1%) Other MSK symptoms (not axSpA-related) 14 (15%) 6 (6%) 20 (11%) Mild infectious disease 2 (2%) 2 (2%) 4 (2%) Other 8 (9%) 2 (2%) 10 (5%) Severe adverse events 3 (3%) 1 (1%) 4 (4%) Death 0 (0%) 0 (0%) 0 (0%) Seizure 0 (0%) 1 (1%) 1 (1%) Severe Flare 1 (1%) 0 (0%) 1 (1%) Severe Infection 1 (1%) 0 (0%) 1 (1%) Hip Replacement 1 (1%) 0 (0%) 1 (1%) Device-related adverse events na 0 (0%) (0%) Abbreviations: axSpA, axial Spondyloarthritis; MSK = musculoskeletal, na, not applicable. Additional Declarations Yes there is potential Competing Interest. Applimeda is the developer and rights holder of Axia. M.lM., T.H., and R.L. are shareholders, partners, or employees of Applimeda. All other authors are not financially dependent on Applimeda. Supplementary Files CONSORT2025editablechecklistbechterewapptrial.docx CONSORT_2025_checklist_bechterew-app_trial.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7526871","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":514191013,"identity":"b0adcfca-551d-4854-aa31-d7993508a350","order_by":0,"name":"Patrick-Pascal Strunz","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAt0lEQVRIiWNgGAWjYBAC+QYIXc/PwAak2IjQYnAMQifObCBaC1RR4oYDRGuR730mXfCHIXHzjbQ0CYYyG8Ja5NvYzaRn8DDUm91IOybBcC6NCGuOsbFJ80gwJJjdSG+7wdh2mFgtBgwJxjPAWv4TqyWBIcFAIu0YUMsBwjoMjqUxW/McYEiQOPMs/UfCuWTCWuSbjzHe5vnDkMDfnmZs8KHMjgiHQQDUCwlEaxgFo2AUjIJRgBcAAC3UMkHNNYK9AAAAAElFTkSuQmCC","orcid":"","institution":"University Hospital of Wuerzburg","correspondingAuthor":true,"prefix":"","firstName":"Patrick-Pascal","middleName":"","lastName":"Strunz","suffix":""},{"id":514191014,"identity":"6c5a4e78-e668-418a-ac37-66ddfeafe46e","order_by":1,"name":"Matthias Froehlich","email":"","orcid":"","institution":"University Hospital of Wuerzburg, Medicine II, Rheumatology/ Clinical Immunology","correspondingAuthor":false,"prefix":"","firstName":"Matthias","middleName":"","lastName":"Froehlich","suffix":""},{"id":514191015,"identity":"4366b6f9-97a8-48e0-b3bf-8049f4310b95","order_by":2,"name":"Tobias Heusinger","email":"","orcid":"","institution":"University of Wuerzburg, Medical Faculty","correspondingAuthor":false,"prefix":"","firstName":"Tobias","middleName":"","lastName":"Heusinger","suffix":""},{"id":514191016,"identity":"4ca73be7-162d-422a-bdef-59dee1e8a0c3","order_by":3,"name":"Maxime Le Maire","email":"","orcid":"","institution":"University of Wuerzburg, Medical Faculty","correspondingAuthor":false,"prefix":"","firstName":"Maxime","middleName":"Le","lastName":"Maire","suffix":""},{"id":514191017,"identity":"1d07af80-5c93-4994-bff8-4fe38a2787d4","order_by":4,"name":"Anna Fleischer","email":"","orcid":"","institution":"University Hospital of Wuerzburg, Medicine II, Psycosomatics","correspondingAuthor":false,"prefix":"","firstName":"Anna","middleName":"","lastName":"Fleischer","suffix":""},{"id":514191018,"identity":"f075bd3a-7360-4ef2-b2eb-0054f3fcf96b","order_by":5,"name":"Karsten Luetkens","email":"","orcid":"","institution":"University Hospital Wuerzburg, Department of Diagnostic and Interventional Radiology","correspondingAuthor":false,"prefix":"","firstName":"Karsten","middleName":"","lastName":"Luetkens","suffix":""},{"id":514191019,"identity":"61360144-065f-4c75-a6d1-79fc2a06553a","order_by":6,"name":"Patricia Possler","email":"","orcid":"","institution":"University of Wuerzburg, Medical Faculty","correspondingAuthor":false,"prefix":"","firstName":"Patricia","middleName":"","lastName":"Possler","suffix":""},{"id":514191020,"identity":"d716680d-95c5-496a-b521-1a242f05b100","order_by":7,"name":"Michael Gernert","email":"","orcid":"","institution":"University Hospital of Wuerzburg, Medicine II, Rheumatology/ Clinical Immunology","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Gernert","suffix":""},{"id":514191021,"identity":"4b4dc0bf-15b1-42d7-aa8f-1dee3e827b35","order_by":8,"name":"Hannah Labinsky","email":"","orcid":"","institution":"University of Erlangen-Nuremberg","correspondingAuthor":false,"prefix":"","firstName":"Hannah","middleName":"","lastName":"Labinsky","suffix":""},{"id":514191022,"identity":"b0010944-6a57-4b12-b9c2-c0b76670b53a","order_by":9,"name":"Ottar Gadeholt","email":"","orcid":"https://orcid.org/0000-0001-6320-4818","institution":"Rheumatologische Schwerpunktpraxis Wuerzburg","correspondingAuthor":false,"prefix":"","firstName":"Ottar","middleName":"","lastName":"Gadeholt","suffix":""},{"id":514191023,"identity":"3de8c565-46a5-4e07-9bde-8659607e4e2a","order_by":10,"name":"Robert Leppich","email":"","orcid":"","institution":"Chair of Software Engineering (Informatik II), Department of Computer Science, University of Wuerzburg","correspondingAuthor":false,"prefix":"","firstName":"Robert","middleName":"","lastName":"Leppich","suffix":""},{"id":514191024,"identity":"652605a5-2d1f-4617-a21c-268746f214bd","order_by":11,"name":"Astrid Schmieder","email":"","orcid":"","institution":"University Hospital Wuerzburg, Department of Dermatology, Venereology, and Allergology","correspondingAuthor":false,"prefix":"","firstName":"Astrid","middleName":"","lastName":"Schmieder","suffix":""},{"id":514191025,"identity":"62af2494-b8bd-43f0-a3dd-18206cf875c2","order_by":12,"name":"Ludwig Hammel","email":"","orcid":"","institution":"Deutsche Vereinigung Morbus Bechterew e. V.","correspondingAuthor":false,"prefix":"","firstName":"Ludwig","middleName":"","lastName":"Hammel","suffix":""},{"id":514191026,"identity":"583b6582-0370-47e7-b9c1-3009975ecd33","order_by":13,"name":"Billy Sperlich","email":"","orcid":"","institution":"Integrative and Experimental Exercise Science and Training, Institute for Sports Science, University of Wuerzburg","correspondingAuthor":false,"prefix":"","firstName":"Billy","middleName":"","lastName":"Sperlich","suffix":""},{"id":514191027,"identity":"7f1833b9-cfb8-4fcb-b4ea-c3548515f9bd","order_by":14,"name":"Hermann Einsele","email":"","orcid":"https://orcid.org/0000-0002-7680-0819","institution":"University Hospital Würzburg","correspondingAuthor":false,"prefix":"","firstName":"Hermann","middleName":"","lastName":"Einsele","suffix":""},{"id":514191028,"identity":"4c0551a1-5636-4129-8632-5a3ad10f942d","order_by":15,"name":"Marc Schmalzing","email":"","orcid":"","institution":"University Hospital of Wuerzburg, Medicine II, Rheumatology/ Clinical Immunology","correspondingAuthor":false,"prefix":"","firstName":"Marc","middleName":"","lastName":"Schmalzing","suffix":""}],"badges":[],"createdAt":"2025-09-03 12:10:25","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7526871/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7526871/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":91931517,"identity":"d3323c4a-ac49-4fad-a46a-c515fa9e042a","added_by":"auto","created_at":"2025-09-23 02:31:22","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":265711,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCONSORT flow diagram of the trial\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7526871/v1/e430d6a2d360c5a96d417a3e.jpg"},{"id":91931516,"identity":"c522b5a3-a65f-4f0a-ae20-36ee4b699d2f","added_by":"auto","created_at":"2025-09-23 02:31:22","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":204525,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eResults of the primary outcomes in the intention-to-treat population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(a, c, e,) The Axia intervention significantly improved mean disease activity (BASDAI), functionality (BASFI), and quality of life (ASQoL) compared to baseline, whereas no significant changes were observed in the control group. (b, d, f,) ANCOVA analyses, adjusted for baseline values and sex, confirmed significantly greater improvements for BASDAI, BASFI, and ASQoL in the intervention group than in the control group. (g, h,) The proportion of participants achieving ASAS20 and ASAS40 responses was significantly higher in the intervention group. ***: p \u0026lt; 0.001.\u003c/p\u003e\n\u003cp\u003eAbbreviations: ASQoL, Ankylosing Spondylitis Quality of Life Questionnaire; ASAS, Assessment of Spondyloarthritis International Society; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; BASFI, Bath Ankylosing Spondylitis Functional Index.\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7526871/v1/47791ff34dbb6de01e548fd1.jpg"},{"id":91934083,"identity":"a583c27a-4aee-496f-9ba6-38eb3dba405e","added_by":"auto","created_at":"2025-09-23 02:39:22","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":212361,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eResults of the secondary outcomes in the intention-to-treat population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(a, c, e, g) The Axia intervention significantly improved the means of self-efficacy (ASKU), health literacy (HLS-EU Q16), pain (NRS pain), and patient global assessment (NRS PtGA) compared to baseline while no changes were observed in the control group. (b, d, f, h) ANCOVA analyses, adjusted for baseline values and sex,confirmed significantly greater improvements for ASKU, NRS pain, and NRS PtGA in the intervention group than in the control group. Differences in HLS-EU Q16 between intervention and control group were not significant in ANCOVA analysis. **: p\u0026lt;0.01, ***: p \u0026lt; 0.001.\u003c/p\u003e\n\u003cp\u003eAbbreviations: ASKU, Allgemeine Selbstwirksamkeit Kurzskala (German language questionnaire for self efficacy) ; HLS-EU Q16, 16‑Item European Health Literacy Survey Questionnaire; NRS, numeric rating scale; PtGA, patient global assessment.\u003c/p\u003e","description":"","filename":"Picture3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7526871/v1/20bb9d58d90f9ffb9f4529c6.jpg"},{"id":94182058,"identity":"46f4ecd4-0be1-4a41-9b77-4b4e31b5653f","added_by":"auto","created_at":"2025-10-23 09:40:13","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1781553,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7526871/v1/09f077f8-194b-46c0-a494-2b2b0b9ddaf4.pdf"},{"id":91931518,"identity":"e4df985c-28de-4cb7-8690-ccb621dad986","added_by":"auto","created_at":"2025-09-23 02:31:22","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":33225,"visible":true,"origin":"","legend":"CONSORT_2025_checklist_bechterew-app_trial.docx","description":"","filename":"CONSORT2025editablechecklistbechterewapptrial.docx","url":"https://assets-eu.researchsquare.com/files/rs-7526871/v1/1702fc0854bfde99a3fcbe68.docx"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential Competing Interest.\nApplimeda is the developer and rights holder of Axia. M.lM., T.H., and R.L. are shareholders, partners, or employees of Applimeda. All other authors are not financially dependent on Applimeda.","formattedTitle":"The novel digital therapeutic Axia improves disease activity, functionality, and quality of life in axial spondyloarthritis patients: a randomized controlled trial","fulltext":[{"header":"Main","content":"\u003cp\u003eNon-pharmacological interventions such as physical activity and patient education are a cornerstone in the management of axial spondyloarthritis (axSpA), an inflammatory rheumatic and musculoskeletal disease (iRMD) characterized by chronic inflammation of the axial skeleton\u0026nbsp;[1]. In particular, home-based exercise (HbE) has been shown to improve disease activity, physical function and quality of life\u0026nbsp;[2], and is thus strongly recommended in national and international guidelines [3-5].\u003c/p\u003e\n\u003cp\u003eHowever, the effective translation of these recommendations in real-world clinical practice remains a major challenge, as a considerable proportion of patients underutilize or fail to adhere to such measures, particularly exercise therapy [6]. This lack of sustained engagement has far-reaching consequences, as patients who do not engage in regular exercise interventions are more likely to experience progressive functional and mobility limitations, higher disease activity, and poorer disease-related quality of life [7].\u003c/p\u003e\n\u003cp\u003eDigital therapeutics (DTx) may offer a scalable solution to this gap by delivering structured, individualized interventions directly to patients in their everyday environments [8, 9]. In doing so, DTx may reduce key barriers to adherence, including limited access to physiotherapy, time constraints, and motivational challenges \u0026nbsp;[10, 11]. Despite growing interest and development efforts, however, no DTx in rheumatology has yet demonstrated clinically meaningful improvements in disease activity in a large-scale randomized controlled trial (RCT) [9]. This evidentiary gap currently limits their integration into standard care pathways.\u003c/p\u003e\n\u003cp\u003eTo address these gaps, the DTx \u003cem\u003eAxia\u0026nbsp;\u003c/em\u003ewas developed by a start-up of two medical students in collaboration with the University Hospital of Wuerzburg, and the German axSpA patient self-help association\u0026nbsp;[12]. Axia is designed to provide axSpA-specific HbE and structured patient education, complemented by additional disease self-management tools. Gamification elements are integrated to enhance engagement and maximize adherence to therapy\u0026nbsp;[12].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo prove Axia’s efficacy, we conducted the Bechterew-App Trial, a three-phase randomized controlled trial (RCT) involving 200 axSpA patients with stable pharmacotherapy (German registry of clinical trials (DRKS), DRKS-ID: DRKS00033783).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo our knowledge, this represents the first large-scale RCT in rheumatology to demonstrate that a DTx can produce clinically meaningful improvements in disease activity, function and disease-specific quality of life, thereby providing a robust evidence base that may facilitate the future integration of DTx into standard rheumatology care.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eRecruitment and Baseline Characteristics\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipants were recruited nationwide in Germany between March 2024 and December 2024 with the support of patient self-help associations, social media, and rheumatology practices. Of 453 individuals screened for eligibility, 200 were enrolled and randomized 1:1 to receive either Axia or standard of care for 12 weeks.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe primary outcome assessment was conducted at week 12 and completed by 186 participants. The main reason for discontinuation was withdrawal of informed consent; one participant was lost to follow-up (Fig. 1).\u003c/p\u003e\n\u003cp\u003eBaseline characteristics for the intention-to-treat population (n=187) are shown in Table 1. Apart from a slightly higher proportion of female participants in the intervention group, no relevant differences were observed. Age, use of biological (b)DMARDs or targeted synthetic (ts)DMARDs, physiotherapy, and exercise behavior were well balanced between groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter 12 weeks, participants in the \u003cem\u003eAxia\u0026nbsp;\u003c/em\u003eintervention group showed significantly greater improvements in disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]; ANCOVA-estimated group difference: -1.508; 95% Confidence Interval (CI): -1.874 to -1.142; p\u0026lt;0.001), functional status (Bath Ankylosing Spondylitis Functional Index [BASFI]; -1.139; 95% CI: -1.524 to -0.755; p\u0026lt;0.001) and disease-specific quality of life (Ankylosing Spondylitis Quality of Life questionnaire [ASQoL]; -2.297; 95% CI: -2.983 to -1.610; p\u0026lt;0.001) (Fig. 2). All effects exceeded their respective minimal clinically important difference (MCID) thresholds. Effect sizes were large across all primary outcomes, with Cohen’s \u003cem\u003ed\u003c/em\u003e values of 1.20 for disease activity, 0.87 for functional status, and 0.97 for quality of life.\u003c/p\u003e\n\u003cp\u003eParticipants were instructed to remain on stable anti-rheumatic pharmacotherapy during the trial to minimize the potential influence of treatment changes. Nevertheless, some treatment switches occurred. To assess their impact, the primary outcomes of the per-protocol (PP) population were compared to the intention-to-treat (ITT) population. Effect estimates in the PP population were numerically higher and consistent in direction with the ITT analysis, indicating that protocol deviations, including treatment modifications, had no substantial impact on the results (Table 2).\u003c/p\u003e\n\u003cp\u003eRobustness of the findings was further evaluated through additional ANCOVA analyses adjusting for sex. No significant influence was observed, and treatment effects remained virtually unchanged, suggesting that the slight imbalance in sex distribution did not materially influence the outcomes (Table 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSecondary Outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSecondary outcomes included response rates according to the Assessment of Spondyloarthritis International Society (ASAS)20 and ASAS40 criteria, as well as changes in global pain, patient global assessment (PtGA), self-efficacy, health literacy. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter 12 weeks of app use, significantly more participants in the intervention group met the ASAS20 (51% vs. 9%; p\u0026lt;0.001) and ASAS40 (23% vs. 3%; p\u0026lt;0.001) response criteria compared to the control group (Fig. 3). Adjusted ANCOVA models showed significant group differences in favor of the intervention for global pain, PtGA, self-efficacy, and exercise adherence. No significant difference was observed for health literacy (Fig. 3).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdherence rates\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn addition to self-reported adherence, participants’ usage of \u003cem\u003eAxia\u003c/em\u003e was objectively tracked: During the 12-week-period, the app was used on an average of 69 days (SD 18.3), and cumulatively, for an average of 1145 mins (SD 937.6 mins). A total of 77.9% of participants used the app on at least five days a week, and 29.7% used \u003cem\u003eAxia\u003c/em\u003e daily. On at least half of the days, the app was used by 93% of participants. 98.9% of the participants of the intervention group stated that they would like to continue using Axia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSafety\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll adverse events (AE) were assessed during the trial. In total, 55 AEs (29%) were observed, 4 of which were severe AEs (SAE). AE incidence rates of the intervention group (22%, n=21; 1% SAE, n=1) were lower than in the control group (37%, n=34; 3% SAE, n=3). No device-related AEs were identified in the intervention group. Table 3 lists all observed AEs.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis RCT provides the first robust evidence that a DTx can achieve clinically meaningful improvements in disease activity, functional status, and quality of life in axSpA patients receiving stable pharmacotherapy. The Bechterew-App Trial met all three primary endpoints, demonstrating that Axia - an app-based, multimodal intervention integrating exercise therapy, patient education, and self-management support - may serve as a scalable, non-pharmacological treatment modality for axSpA. To our knowledge, this is the first large-scale, methodologically rigorous RCT to show that a DTx can significantly reduce disease activity in an iRMD.\u003c/p\u003e\n\u003cp\u003eThe efficacy observed with Axia represents a marked advance over previous digital health studies in rheumatology. The positive effects of non-pharmacological therapies for axSpA are well-established, mostly from interventions delivered in traditional formats such as printed manuals or booklets [2, 13, 14]. In recent years, several DTx-supported interventions have been explored [15, 16]. However, these studies have often suffered from methodological limitations, including small sample sizes, non-disease-specific applications, or insufficient control designs. Crucially, none of these DTx achieved significant or clinically relevant improvements in key outcomes such as disease activity, functional status or quality of life [15, 16]. In contrast, the Bechterew-App Trial provides high-quality evidence that a DTx, specifically tailored to axSpA, can achieve such outcomes.\u003c/p\u003e\n\u003cp\u003eThe magnitude of the treatment effects observed in this trial is clinically noteworthy. The ASAS20 and ASAS40 response criteria are commonly used as primary or secondary endpoints in pharmacological trials for axSpA \u0026nbsp;[17-20]. Historically, exercise interventions have shown only modest effects on disease activity [21], and consequently, robust data on their impact on ASAS20 or ASAS40 responses are lacking. In this trial, the intervention group achieved ASAS20 and ASAS40 response rates of 51% and 23%, respectively, compared with 9% and 3% in the control group. For context, trials with tumor necrosis factor inhibitors (TNFi) typically report ASAS20 response rates of around 65% and ASAS40 rates between 39% and 48% [22]. A meta-analysis by Betts et al. found ASAS20 responses ranging from 50.5% to 71.7% for TNFi and interleukin-17 inhibitors, with placebo groups achieving around 27.9% for ASAS20 and 13.5% for ASAS40 [23].\u0026nbsp;While these figures offer a useful benchmark, differences in study design, blinding, and patient selection inevitably preclude direct head-to-head comparison and caution against interpreting the present results as evidence of equal or comparable efficacy to pharmacological treatments. Nevertheless, the magnitude of the ASAS20 and ASAS40 responses underscores the high therapeutic potential of Axia, and - more broadly - of DTx approaches in iRMDs.\u003c/p\u003e\n\u003cp\u003eThe pronounced efficacy of Axia may be attributable to its low-threshold, location-independent accessibility as well as its multimodal, gamified design, which integrates physical activity, patient education, and behavioral support within a single digital platform. In addition, unlike generic exercise applications, Axia was developed exclusively for axSpA, integrating targeted exercise therapy tailored to the pathophysiology and movement limitations of this condition\u0026nbsp;[12].\u003c/p\u003e\n\u003cp\u003eAnother factor that may explain its superior effectiveness compared with conventional home-based exercise approaches is the holistic physical activity concept deployed in this trial. The DTx provides patients with a variety of options to increase physical activity, including patient-tailored axSpA-specific HbE of varying durations, cardiovascular-focused training sessions, targeted HbE-modules for acute pain and morning stiffness, as well as direct promotion of sports participation alongside general activity enhancement through features such as daily step goals, a built-in step counter, and smartwatch integration [12]. Additionally, Axia especially encourages the integration of brief, highly accessible exercise habits into daily routines, such as linking one or two short exercises with a daily routine like getting out of bed or brewing coffee [12]. This contrasts with many other exercise DTx that focus primarily on longer, fixed sessions (e.g., 20 minutes in the evening) [15, 16]. Combining a wide range of exercise options and encouraging short, distributed bouts of activity embedded into everyday life may therefore represent a promising approach for exercise-based DTx in iRMDs and other chronic diseases.\u003c/p\u003e\n\u003cp\u003eSustaining long-term adherence is a recognized challenge in both exercise interventions and DTx, with low engagement and high attrition frequently cited as key barriers to efficacy [24, 25]. As personal communication is known to enhance adherence to DTx by motivating the user\u0026nbsp;[25], the Bechterew-App Trial was deliberately designed to simulate real-world conditions by avoiding such interactions and to minimize potential adherence bias. After enrollment, interaction was limited to baseline allocation and post-assessment follow-up, with no motivational prompts. Accordingly, no proactive contact was initiated with study participants during this period and only channels for participant inquiries were made available. With a total of 77.9% of participants using the DTx on at least five days a week over a 12-week-period, Axia still achieved adherence and usage rates far exceeding those reported in other axSpA DTx trials in real-world settings [24, 25]. Gamification features - such as daily activity streaks, milestone tracking, and point rewards - may have contributed to sustained engagement and the observed treatment effects. Moreover, the possibility of perceiving early improvements in pain and mobility could have created a reinforcing feedback loop that further encouraged continued use. However, it remains uncertain whether such high adherence rates observed under trial conditions can be maintained in routine clinical practice, where external accountability and structured follow-up are often absent. Further pragmatic and longitudinal studies are needed to determine whether the observed engagement and clinical benefits are sustainable. Long-term follow-up studies of the Bechterew-App Trial are currently underway to address these questions.\u003c/p\u003e\n\u003cp\u003eThe findings of this trial also have relevance beyond axSpA. In Germany, Axia has been submitted for approval as a reimbursable digital health application (DiGA) under the national fast-track pathway for prescription DTx. If approved, Axia could be made available to all eligible patients nationwide, providing a scalable, low-barrier treatment option that complements existing pharmacological and non-pharmacological therapies [26]. Planned translations into additional languages and implementation in other European countries as well as the United States may also enable broader access to structured, evidence-based exercise therapy for axSpA in health systems where such programs are limited or inconsistently provided. The underlying therapeutic approach - disease-specific, adaptive exercise combined with patient education, behavioral support, and gamification elements - represents a framework that could be adapted for other iRMDs in which exercise and self-management are integral to care but long-term adherence is suboptimal.\u003c/p\u003e\n\u003cp\u003eRegarding safety, no concerning safety signals were observed, especially no device-related AEs.\u003c/p\u003e\n\u003cp\u003eThe main limitation of this study is the absence of a double-blinded design and a placebo group. This is a common challenge in RCTs involving DTx, as participants can often easily unblind themselves by reviewing the internet on the content and function of the verum app.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBlinding of the study personnel was also not implemented; however, as per protocol, no direct contact occurred after group allocation, and all questionnaires were self-reported and completed by participants at home via electronic case report forms (eCRFs), minimizing the potential for investigator-induced bias.\u0026nbsp;A further limitation is the exclusive reliance on patient-reported outcome measures (PROMs) without objective clinical or biomarker-based endpoints. While the remote design and nationwide recruitment precluded on-site assessments in the Bechterew-App Trial, future studies should integrate objective endpoints where feasible.\u003c/p\u003e\n\u003cp\u003eIn a small number of cases (five participants in the intervention group and eight participants in the control group), baseline data had to be deleted in accordance with data protection regulations, as consent to participate in the study was withdrawn. While this is a limitation, all withdrawals occurred prior to the 12-week assessment, and the small number of cases reduces the likelihood of systematic bias.\u003c/p\u003e\n\u003cp\u003eKey strengths of this trial include the large sample size and the high proportion of complete datasets, both of which enhance statistical power and minimize attrition bias. Moreover, the demographic and treatment characteristics of the study population - including the frequency of bDMARD and NSAID use, physiotherapy treatment, and levels of HbE and other sports activities - were closely aligned with those reported in recent national real-world observational studies [27, 28], supporting representativeness. The higher mean BASDAI in our trial (5.17 vs. 3.9 in the ATTENTUS study\u0026nbsp;[28]) reflects the inclusion criterion of BASDAI ≥ 3.5, which was applied to reduce heterogeneity and ensured that treatment effects were evaluated in patients with at least moderate disease activity. Women were overrepresented, likely reflecting the higher uptake of digital health applications among women, who account for approximately 73% of DHA users according to national health insurance data [29]. Another strength is the low-threshold participation enabled by the remote design, which facilitated inclusion of patients from across Germany without on-site visits.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn conclusion, the Bechterew-App Trial provides the first large-scale, methodologically rigorous evidence that a disease-specific, app-based multimodal intervention can achieve significant and clinically meaningful improvements in disease activity, functional status, and quality of life in axSpA patients receiving stable pharmacotherapy. These findings support the potential of Axia to complement existing pharmacological and non-pharmacological treatments and help close the gap between guideline-based exercise recommendations and their limited implementation in routine care. While the absence of blinding, reliance on PROMs, and the short intervention period warrant cautious interpretation, the magnitude of the observed effects and high adherence rates under real-world-like conditions justify further pragmatic and long-term evaluations. The Axia approach could also serve as a model for other iRMDs, where structured exercise and self-management are central to care but long-term adherence remains a challenge.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data underlying the results of this clinical trial are included in the article and its supplementary materials. To protect participant confidentiality and proprietary content, deidentified individual-level data are available upon reasonable request and subject to restricted access. Requests should be directed to the corresponding author P.-P. Strunz and must include a brief research proposal specifying the intended use.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe use of a custom code is not applicable in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe abstract of this study was presented as oral presentation at the EULAR congress 2025 in Barcelona (LB0002). We would like to thank all the patients who participated in the trial. Furthermore, we also would like to thank the German patient self-help association (DVMB) for supporting us. We are also grateful to our statisticians Dr. Victoria R\u0026uuml;cker and Dr. Uwe Malzahn for performing the sample size calculation. Applimeda is the developer and rights holder of Axia. M.lM., T.H., and R.L. are shareholders, partners, or employees of Applimeda. All other authors are not financially dependent on Applimeda.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: P.-P.S., M.F., T.H., M.lM., M.S.\u003c/p\u003e\n\u003cp\u003eMethodology: P.-P.S., M.F., T.H., M.lM., M.S., A.F., K.S.L., H.L., A.S., B.S.\u003c/p\u003e\n\u003cp\u003eInvestigation: P.-P.S., M.F., T.H., M.lM., M.S., P.Po., O.G.\u003c/p\u003e\n\u003cp\u003eFormal Analysis: P.-P.S., M.F., T.H., M.lM., M.S., P.Po.\u003c/p\u003e\n\u003cp\u003eWriting \u0026ndash; Original Draft: P.-P.S., M.F., T.H., M.lM., M.S.\u003c/p\u003e\n\u003cp\u003eWriting \u0026ndash; Review \u0026amp; Editing: P.-P.S., M.F., T.H., M.lM., A.F., K.S.L., P.Po., M.G., H.L., O.G., R.L., A.S., L.H., B.S., H.E., M.S.\u003c/p\u003e\n\u003cp\u003eAll authors reviewed and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eP.-P.S. received speaker\u0026rsquo;s fees and travel grants from Janssen-Cilag, Galapagos, Eli Lilly, Boehringer/Ingelheim and AbbVie (less than US$10,000 each) as well as research funding from Chugai (US$25,000), Novartis (US$150,000) and AbbVie (US$ 12,000). M.lM. reported to be Chief Executive Officer of Applimeda, Co-Founder and shareholder of Applimeda GmbH. T.H. reported to be Chief Regulatory \u0026amp; Medical Officer of Applimeda, Co-Founder and shareholder of Applimeda GmbH. J.K. stated to be PRRC of Applimeda. H.L. received travel grants from UCB, Boehringer Ingelheim, Pfizer and AbbVie as well as compensation for consulting activity from Pfizer and for lecturing activities from Janssen. A.F., K.S.L., P.Po., O.G., H.E., and A.S. declared no conflict of interest. M.G. received travel grants, compensation for advisory boards or speaker\u0026rsquo;s fees from AbbVie, Chugai, Eli Lilly, Hexal, Janssen, Novartis, Pfizer and Takeda and research funding from Novartis (US$150,000) . R.L. declared to be Chief Technology Officer of Applimeda, Co-Founder and shareholder of Applimeda GmbH. L.H. declared to be Former Chief Executive Officer of DVMB. E.S. declared to be Chief Executive Officer of DVMB. B.S. declared no conflict of interest. M.F. received speaker\u0026rsquo;s fees, travel grants or compensation for board memberships from AbbVie, Novartis, Janssen and Eli Lilly. M.S. received speaker\u0026rsquo;s fees, travel grants, research funding or compensation for consultancies or board memberships from AbbVie, Actelion, AstraZeneca, BMS, Boehringer/Ingelheim, Celgene, Chugai/Roche, Eli Lilly, Genzyme, Gilead, Hexal/Sandoz, Janssen-Cilag, MSD, Novartis, Pfizer, Sanofi Pasteur, Takeda (Shire) and UCB (less than US$10,000 each) and research funding from Novartis (US$150,000).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSieper, J., Braun, J., Dougados, M. \u0026amp; Baeten, D. Axial spondyloarthritis. Nat. Rev. Dis. Primers 1, 15013 (2015). https://doi.org/10.1038/nrdp.2015.13\u003c/li\u003e\n\u003cli\u003eAytekin, E., Caglar, N.S., Ozgonenel, L., Tutun, S., Demiryontar, D.Y. \u0026amp; Demir, S.E. 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Rheumatol. 78 (Suppl 1), 3\u0026ndash;64 (2019). https://doi.org/10.1007/s00393-019-0670-3\u003c/li\u003e\n\u003cli\u003eWard, M.M. et al. 2019 Update of the American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network recommendations for the treatment of ankylosing spondylitis and non-radiographic axial spondyloarthritis. Arthritis Rheumatol. 71, 1599\u0026ndash;1613 (2019). https://doi.org/10.1002/art.41042\u003c/li\u003e\n\u003cli\u003eStrunz, P.P. et al. Apps in der Rheumatologie: Bedarf es einer App in der Therapie der axialen Spondyloarthritis? Z. Rheumatol. 82, 256\u0026ndash;261 (2023). https://doi.org/10.1007/s00393-021-01104-1\u003c/li\u003e\n\u003cli\u003eCarbo, M., Hilberdink, B., Paap, D. et al. Physical activity in relation to health status, quality of life and compliance with World Health Organization recommendations in patients with axial spondyloarthritis. Arthritis Res. Ther. 27, 112 (2025). https://doi.org/10.1186/s13075-025-03575-y\u003c/li\u003e\n\u003cli\u003eNajm, A. et al. EULAR points to consider for the development, evaluation and implementation of mobile health applications aiding self-management in rheumatic and musculoskeletal diseases. RMD Open 5, e001014 (2019). https://doi.org/10.1136/rmdopen-2019-001014\u003c/li\u003e\n\u003cli\u003eKnitza, J., Gupta, L. \u0026amp; H\u0026uuml;gle, T. Rheumatology in the digital health era: status quo and quo vadis? Nat. Rev. Rheumatol. 20, 747\u0026ndash;759 (2024). https://doi.org/10.1038/s41584-024-01177-7\u003c/li\u003e\n\u003cli\u003eLee, A.Z.Y., Woon, T.H., Wang, C.T.M., Kwan, Y.H. \u0026amp; Fong, W. Facilitators and barriers to physical activity for patients with rheumatoid arthritis and axial spondyloarthritis. Int. J. Rheum. Dis. 28, e70109 (2025). https://doi.org/10.1111/1756-185X.70109\u003c/li\u003e\n\u003cli\u003eIken, A. et al. Barriers and facilitators for implementing longstanding, personalized exercise therapy in people with rheumatoid arthritis or axial spondyloarthritis and severe functional limitations [poster]. Ann. Rheum. Dis. 84 (Suppl 1), 291 (2025). https://doi.org/10.1136/annrheumdis-2025-eular.D144\u003c/li\u003e\n\u003cli\u003eStrunz, P.P. et al. The exercise-app Axia for axial spondyloarthritis enhances the home-based exercise frequency in patients: a cross-sectional survey. Rheumatol. Int. 44, 1143\u0026ndash;1154 (2024). https://doi.org/10.1007/s00296-024-05600-w\u003c/li\u003e\n\u003cli\u003eDurmus, D., Alayli, G., Cil, E. \u0026amp; Canturk, F. Effects of a home-based exercise program on quality of life, fatigue, and depression in patients with ankylosing spondylitis. Rheumatol. Int. 29, 673\u0026ndash;677 (2009). https://doi.org/10.1007/s00296-008-0756-8\u003c/li\u003e\n\u003cli\u003eKasapoglu Aksoy, M., Birtane, M., Taştekin, N. \u0026amp; Ekuklu, G. Effectiveness of structured group education on ankylosing spondylitis patients. J. Clin. Rheumatol. 23, 138\u0026ndash;143 (2017). https://doi.org/10.1097/RHU.0000000000000499\u003c/li\u003e\n\u003cli\u003eSong, Y., Reifsnider, E., Chen, Y., Wang, Y. \u0026amp; Chen, H. Impact of a theory-based mHealth intervention on disease knowledge, self-efficacy, and exercise adherence among ankylosing spondylitis patients: randomized controlled trial. J. Med. Internet Res. 24, e38501 (2022). https://doi.org/10.2196/38501\u003c/li\u003e\n\u003cli\u003eBlaskowitz, P.P.V.A. et al. Impact of the digital health application ViViRA on spinal mobility, physical function, quality of life and pain perception in spondyloarthritides patients: a randomized controlled trial. Arthritis Res. Ther. 26, 208 (2024). https://doi.org/10.1186/s13075-024-03443-1\u003c/li\u003e\n\u003cli\u003eSieper, J. et al. The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis. Ann. Rheum. Dis. 68 (Suppl 2), ii1\u0026ndash;ii44 (2009). https://doi.org/10.1136/ard.2008.104018\u003c/li\u003e\n\u003cli\u003evan der Heijde, D. et al. Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis (SELECT-AXIS 1): a multicentre, randomized, double-blind, placebo-controlled, phase 2/3 trial. Lancet 394, 2108\u0026ndash;2117 (2019). https://doi.org/10.1016/S0140-6736(19)32534-6\u003c/li\u003e\n\u003cli\u003evan der Heijde, D. et al. Adalimumab effectiveness for the treatment of ankylosing spondylitis is maintained for up to 2 years: long-term results from the ATLAS trial. Ann. Rheum. Dis. 68, 922\u0026ndash;929 (2009). https://doi.org/10.1136/ard.2007.087270\u003c/li\u003e\n\u003cli\u003eDeodhar, A. et al. Efficacy and safety of intravenous secukinumab in patients with active axial spondyloarthritis: results from a randomized, placebo-controlled, phase 3 study. Arthritis Rheumatol. 77, 163\u0026ndash;170 (2025). https://doi.org/10.1002/art.42993\u003c/li\u003e\n\u003cli\u003eMartins, N.A., Furtado, G.E., Campos, M.J., Leit\u0026atilde;o, J.C., Filaire, E. \u0026amp; Ferreira, J.P. Exercise and ankylosing spondylitis with New York modified criteria: a systematic review of controlled trials with meta-analysis. Acta Reumatol. Port. 39, 298\u0026ndash;308 (2014).\u003c/li\u003e\n\u003cli\u003eKiltz, U., Tsiami, S., Kiefer, D., Baraliakos, X., B\u0026uuml;hring, B. \u0026amp; Braun, J. Assessments und Outcome-Parameter bei axialer Spondyloarthritis. Aktuelle Rheumatol. 44, 332\u0026ndash;338 (2019). https://doi.org/10.1055/a-0982-3633\u003c/li\u003e\n\u003cli\u003eBetts, K.A. et al. Network meta-analysis and cost per responder of TNF-\u0026alpha; and interleukin inhibitors in the treatment of active ankylosing spondylitis. Rheumatol. Ther. 3, 323\u0026ndash;336 (2016). https://doi.org/10.1007/s40744-016-0038-y\u003c/li\u003e\n\u003cli\u003eLabinsky, H., Gupta, L., Raimondo, M.G., Schett, G. \u0026amp; Knitza, J. Real-world usage of digital health applications (DiGA) in rheumatology: results from a German patient survey. Rheumatol. Int. 43, 713\u0026ndash;719 (2023). https://doi.org/10.1007/s00296-022-05261-7\u003c/li\u003e\n\u003cli\u003eDruce, K.L., Dixon, W.G. \u0026amp; McBeth, J. Maximizing engagement in mobile health studies: lessons learned and future directions. Rheum. Dis. Clin. North Am. 45, 159\u0026ndash;172 (2019). https://doi.org/10.1016/j.rdc.2019.01.004\u003c/li\u003e\n\u003cli\u003eDittrich, F., Mielitz, A., Pustozerov, E., Lawin, D., von Jan, U. \u0026amp; Albrecht, U.V. Digital health applications from a government-regulated directory of reimbursable health apps in Germany: a systematic review for evidence and bias. Mhealth 9, 35 (2023). https://doi.org/10.21037/mhealth-23-17\u003c/li\u003e\n\u003cli\u003eAlbrecht, K. et al. Current data on rheumatological care: annual report from the National database (NDB) of the regional collaborative arthritis centres in Germany. Z. Rheumatol. 83, 666\u0026ndash;674 (2024). https://doi.org/10.1007/s00393-024-01497-9\u003c/li\u003e\n\u003cli\u003eMeyer-Olson, D., Hoeper, K., Hammel, L., Lieb, S., Haehle, A. \u0026amp; Kiltz, U. Nonpharmacological treatment measures, rehabilitation services and membership in patient support groups in axial spondylarthritis (The ATTENTUS axSpA study). Z. Rheumatol. 83, 500\u0026ndash;509 (2024). https://doi.org/10.1007/s00393-023-01410-w\u003c/li\u003e\n\u003cli\u003eGKV Spitzenverband. DiGA-Bericht 2025. https://www.gkv-spitzenverband.de/media/dokumente/krankenversicherung_1/telematik/digitales/2024_DiGA-Bericht_final.pdf (2025).\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"30\"\u003e\n \u003cli\u003ePavy, S., Brophy, S. \u0026amp; Calin, A. Establishment of the minimum clinically important difference for the Bath Ankylosing Spondylitis indices: a prospective study. J. Rheumatol. 32, 80\u0026ndash;85 (2005).\u003c/li\u003e\n \u003cli\u003eHaywood, K.L., Garratt, A.M., Jordan, K., Dziedzic, K. \u0026amp; Dawes, P.T. Disease-specific, patient-assessed measures of health outcome in ankylosing spondylitis: reliability, validity and responsiveness. Rheumatology (Oxford) 41, 1295\u0026ndash;1303 (2002). https://doi.org/10.1093/rheumatology/41.11.1295\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Bechterew-App Trial was designed as a monocentric, prospective, randomized controlled interventional trial to evaluate the efficacy of the DTx \u003cem\u003eAxia\u003c/em\u003e in axSpA patients receiving stable pharmacotherapy. Following baseline assessment, participants were randomized in a 1:1 ratio to either the intervention or control group. Randomization was stratified based on whether participants were receiving weekly individual physiotherapy sessions (yes/no).\u003c/p\u003e\n\u003cp\u003eParticipants in the intervention group received access to Axia for a 12-week period in addition to standard of care. The control group received standard of care alone, including pharmacological and non-pharmacological treatment as recommended by their treating physicians. Neither participants nor investigators were blinded.\u003c/p\u003e\n\u003cp\u003eThe study was conducted as a German nationwide remote study led by the University hospital of Wuerzburg, Germany. The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. The study protocol was approved by the ethics committee of the medical faculty of the University of Wuerzburg, Wuerzburg (DE/EKBY13) (Date July 31st, 2023, No 92/23-am). The trial was prospectively registered at the German Clinical Trials Register (DRKS), DRKS-ID: DRKS00033783), date of first registry March, 1\u003csup\u003est\u003c/sup\u003e, 2024.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParticipants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCandidates were eligible for participation in the Bechterew-App Trial if they met all of the following inclusion criteria:\u003c/p\u003e\n\u003col class=\"decimal_type\"\u003e\n \u003cli\u003eAge \u0026ge; 18 years\u003c/li\u003e\n \u003cli\u003eSigned informed consent\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eConfirmed diagnosis of axSpA by an official medical document issued by a physician\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eBASDAI score \u0026ge; 3.5 at screening\u003c/li\u003e\n \u003cli\u003eStable pharmacotherapy regarding axSpA for at least 8 weeks prior to screening, with no planned therapy changes\u003c/li\u003e\n \u003cli\u003eOnly moderate physical activity, defined as: no more than one physiotherapy session per week on average in the last three months; no more than a total of 90 minutes of sports activities per week with sports activities carried out on no more than three days per week; and no more than a total of 50 minutes of axSpA-specific HbE per week on with axSpA-specific HbE done on no more than four days per week.\u003c/li\u003e\n \u003cli\u003eSufficient smartphone proficiency, defined as regular and independent use of any smartphone app in the past\u003c/li\u003e\n \u003cli\u003eOwnership of a personal Android or iOS-compatible smartphone with mobile internet access, meeting the technical requirements to use \u003cem\u003eAxia\u003c/em\u003e\u003c/li\u003e\n \u003cli\u003eSufficient language skills to independently complete self-reported questionnaires\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eCandidates were excluded if they met any one of the following criteria:\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003ePregnancy\u003c/li\u003e\n \u003cli\u003eAny state or disorder (i.e. acute myocardial infarction) not allowing regular exercise performance\u003c/li\u003e\n \u003cli\u003eAny state or disorder for which regular exercise is a contraindication\u003c/li\u003e\n \u003cli\u003eAny contraindication for \u003cem\u003eAxia\u0026nbsp;\u003c/em\u003eusage according to the official instructions of use\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eActive use of another smartphone-based application for axSpA therapy\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eCandidate participants were informed about the study via various publicly accessible media (e.g. print and online media, social media or flyers). The recruitment process was supported by rheumatology practices and the German Association for Bechterew\u0026apos;s Disease (DVMB), a nationwide self-help organisation for people with axSpA, as well as their partners. Interested patients could register at the public available study homepage (https://studie-bechterew.de) to receive the study documents for screening including the screening questionnaire and the informed consent form. Candidates then had to send the completed study documents along with a medical report confirming the diagnosis of axSpA.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter reviewing the study documents, suitable candidates for the trial received a phone call from an investigator physician to verify eligibility and to obtain informed consent. Eligible participants were enrolled in the trial and invited by email to complete the baseline questionnaire via the eCRF Magana Trial Manager by MaganaMed GmbH (https://maganamed.com).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIntervention\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe intervention consisted of using the smartphone application \u003cem\u003eAxia\u003c/em\u003e over a 12-week period. Axia is a German-language, disease-specific, and patient-tailored DTx developed for individuals with axSpA.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe app includes a library of over 250 exercises, delivered via an adaptive algorithm that continuously adjusts the therapeutic program to the patient\u0026rsquo;s individual needs. Specific modules address acute pain and morning stiffness. In addition,\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003cem\u003eAxia\u003c/em\u003e promotes the integration of short, daily exercise routines into everyday life, encourages users to engage in sports activity and maintain an overall active lifestyle, including step-based activity goals with smartwatch compatibility. Beyond exercise therapy, \u003cem\u003eAxia\u003c/em\u003e features a digital patient academy with structured educational content and tools for disease self-management. All components are embedded in a gamified app environment designed to enhance motivation and support long-term adherence.\u003c/p\u003e\n\u003cp\u003eAxia is a Conformit\u0026eacute; Europ\u0026eacute;enne (CE) class I medical device certified under the European Medical Device Regulation (MDR). Axia and its functions have already been described in detail elsewhere\u0026nbsp;[12].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary and secondary endpoints and their assessment\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary endpoints were changes in disease activity (measured by BASDAI), disease-specific functionality (assessed by BASFI), and axSpA-specific quality of life (assessed by ASQoL) after 12 weeks, comparing the intervention group with the control group. All three instruments are standard patient-reported outcome measures (PROM) routinely used in axSpA care and pharmacological trials. Literature-based minimal clinically important differences (MCIDs), pre-defined in the study protocol, were as follows:\u0026nbsp;a reduction of \u0026ge;1.0 point or \u0026ge;22.5% in BASDAI, \u0026ge;0.7 points or \u0026ge;17.5% in BASFI\u0026nbsp;\u003c!--[if supportFields]\u003e\u003cspan style='font-size:10.0pt;line-height:200%;font-family:\"Arial\",sans-serif; mso-bidi-font-weight:bold'\u003e\u003cspan style='mso-element:field-begin'\u003e\u003c/span\u003e\u0026nbsp;CITATION Pav \\l 1031 \u003cspan style='mso-element: field-separator'\u003e\u003c/span\u003e\u003c/span\u003e\u003c![endif]--\u003e[30]\u003c!--[if supportFields]\u003e\u003cspan style='font-size:10.0pt;line-height:200%;font-family:\"Arial\",sans-serif; mso-bidi-font-weight:bold'\u003e\u003cspan style='mso-element:field-end'\u003e\u003c/span\u003e\u003c/span\u003e\u003c![endif]--\u003e, and \u0026ge;1.8 points in ASQoL (equivalent to 10% of the total scale range)\u0026nbsp;\u003c!--[if supportFields]\u003e\u003cspan style='font-size:10.0pt;line-height:200%;font-family:\"Arial\",sans-serif; mso-bidi-font-weight:bold'\u003e\u003cspan style='mso-element:field-begin'\u003e\u003c/span\u003e\u0026nbsp;CITATION Hay \\l 1031 \u003cspan style='mso-element: field-separator'\u003e\u003c/span\u003e\u003c/span\u003e\u003c![endif]--\u003e[31]\u003c!--[if supportFields]\u003e\u003cspan style='font-size:10.0pt;line-height:200%;font-family:\"Arial\",sans-serif; mso-bidi-font-weight:bold'\u003e\u003cspan style='mso-element:field-end'\u003e\u003c/span\u003e\u003c/span\u003e\u003c![endif]--\u003e.\u003c/p\u003e\n\u003cp\u003eAs patients are familiar with answering these questionnaires in clinical routine, no specific training was required. All PROMs were digitalized within the eCRF and completed independently by participants at home, without access to previous responses or interaction with study personnel. Baseline and week-12 assessments were made available via email invitations. To simulate real-world conditions, no financial compensation or additional incentives were provided.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSecondary endpoints included self-efficacy (ASKU), health literacy assessed (German version of the 16‑Item European Health Literacy Survey Questionnaire [HLS-EU Q16]), global pain (numeric rating scale [NRS]), patient global assessment of disease activity (PtGA), and self-reported adherence to exercise therapy (Exercise Adherence Rating Scale[(EARS]). All secondary measures were collected via eCRF at baseline and week 12.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn addition, ASAS20 and ASAS40 response rates were calculated. ASAS20 response was defined as an improvement of at least 20% and at least 1 unit (on a 0-10 scale) from baseline in three of four domains (spinal pain [BASDAI question 2], spinal inflammation [mean of BASDAI questions 5 and 6], physical function [BASFI], and patient global assessment [PtGA]), with no worsening in the remaining domain (defined as a deterioration of \u0026ge;20% or \u0026ge;1 unit). ASAS40 response required an improvement of at least 40% and 2 units in three of the four domains without any worsening in the fourth.\u003c/p\u003e\n\u003cp\u003eAt week 12, participants were also asked via open-ended questions about adverse events and their willingness to continue with Axia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSample size calculation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSample size calculation was performed by the Clinical Trial Center at the University Hospital W\u0026uuml;rzburg (ZKSW). The trial included three primary endpoints - changes in ASQoL, BASDAI, and BASFI from baseline to week 12. To control for type I error due to multiple testing, the overall significance level (\u0026alpha; = 0.05) was conservatively adjusted using Bonferroni correction, resulting in a per-test alpha of 0.0167. An ANCOVA model adjusted for baseline values was pre-specified as the primary analysis method to compare intervention and control group.\u003c/p\u003e\n\u003cp\u003eMeans and standard deviations were derived from prior studies with comparable interventions\u0026nbsp;[2] [13]. \u0026nbsp;Multiple scenarios were considered in calculation based on different correlation assumptions with \u0026rho; varying from 0.3 to 0.7 between baseline and follow-up. ASQoL was identified as the most limiting endpoint in terms of required sample size. Assuming a conservative correlation of \u0026rho; = 0.4, a total of 160 participants (80 per group) was calculated to achieve 90% power. Dropout-rate was estimated to be 20%. To account for this, an additional 20% were added to the 160 participants resulting in a total sample size of 200 participants (100 per group).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRandomization\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe randomization method was stratified block randomization (ratio 1:1) in randomly defined blocks of 4 or 6. The stratification factor was physiotherapy (Regular physiotherapy prior to the study vs. no regular physiotherapy prior to the study). Separate randomization lists were generated by the ZKSW for each stratum and implemented in a secure allocation software. The study team was blinded to the allocation sequence, and group assignment was revealed only after eligibility confirmation and entry of participant data into the system.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary analyzed population was the ITT population. Missing values were replaced using an copy increments in reference approach.\u003c/p\u003e\n\u003cp\u003eThe statistical analysis was carried out by the ZKSW and BioStats GmbH. Primary and secondary outcomes were analyzed by ANCOVA models, adjusted for the respective baseline value, comparing the intervention and control groups after 12 weeks. Due to the slightly higher proportion of women in the intervention group compared to the control group, additional ANCOVA adjustments were made for sex besides adjustment for baseline values. Descriptive statistics, including mean, standard deviation, and minimum/maximum values, were used to summarize baseline characteristics. All mandatory pretests were performed before the ANCOVA was carried out: The residuals were tested for normal distribution, the Breusch-Pagan test and the White-test were used to analyze homoscedasticity, and the regression slopes were tested for homogeneity. If no systematic deviations were found in the graphical residual analysis, ANCOVA was used as the primary analysis method. To address multiple testing and accumulation of alpha errors, the Benjamini-Hochberg method was used to adjust the significance level. The primary endpoint was considered achieved if the statistical analysis using the baseline adjusted ANCOVA described above together with the Benjamini-Hochberg adjustment showed a statistically significant improvement (p\u0026lt;0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDifferences in ASAS20 and ASAS40 response rates between intervention and control group were analyzed by Chi-Suare-test. For all analyses, Prism and R were used. The statistical analysis plan is available as part of the study protocol in the German registry of clinical trials (DRKS-ID: DRKS00033783).\u003c/p\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e1\u003c/strong\u003e\u003cstrong\u003e: Baseline characteristics\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"628\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 319px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntervention (n=95)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl (n=92)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 319px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean age; years (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e50 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e51 (11)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 319px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBASDAI; absolute (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e5.32 (1.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e5.02 (1.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 319px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale Proportion; % (n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e74% (70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e59% (54)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 319px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNSAIDs; % (n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e55% (52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e62% (57)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 319px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ebDMARD or tsDMARD usage; % (n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e56.3% (53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e60.2% (55)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 628px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePhysical Therapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 628px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eProfessional Physiotherapy\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 319px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOnce per week; % (n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e56% (53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e60% (55)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 319px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo Physiotherapy; % (n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e44% (42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e40% (37)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 628px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOther forms of exercise and physical therapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 319px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHome-based Exercise; % (n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e39% (37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e41% (38)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 319px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFunctional training; % (n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e31% (29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e34% (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 319px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOther Sports; % (n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 165px;\"\u003e\n \u003cp\u003e32% (30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 144px;\"\u003e\n \u003cp\u003e34% (31)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003cstrong\u003e: Comparison of ITT and PP analysis\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"649\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 279px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntention-to-treat (ITT) Analysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"top\" style=\"width: 279px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePer-protocol (PP) Analysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntervention\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=95\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=92\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value \u0026sup2;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntervention\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=88\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en=73\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value \u0026sup2;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDelta BASDAI (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e-1.66 (1.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e-0.11 (1.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e- 1.76 (1.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e-0.11 (1.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDelta BASFI (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e-1.12 (1.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e0.06 (1.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e-1.24 (1.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e0.11 (1.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDelta ASQoL (SD)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e-2.51 (2.55)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e-0.16 (2.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e-2.65 (2.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e-0.21 (2.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003e3\u003c/strong\u003e\u003cstrong\u003e: Safety during the 12-week treatment period\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"609\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 349px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdverse Events (AEs)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl group (n=92)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntervention group (n=95)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal (n=187)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 349px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAny adverse event\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e34 (37%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e21 (22%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e55 (29%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 349px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Flare\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e7 (8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e9 (10%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e16 (9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 349px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Uveitis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e1 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 349px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Other MSK symptoms (not axSpA-related)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e14 (15%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e6 (6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e20 (11%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 349px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Mild infectious disease\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e2 (2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e2 (2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e4 (2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 349px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Other\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e8 (9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e2 (2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e10 (5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 349px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSevere adverse events\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e3 (3%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1 (1%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e4 (4%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 349px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Death\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 349px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Seizure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e1 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 349px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Severe Flare\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e1 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 349px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Severe Infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e1 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 349px;\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Hip Replacement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e1 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e1 (1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 349px;\"\u003e\n \u003cp\u003eDevice-related adverse events\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003ena\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85px;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 89px;\"\u003e\n \u003cp\u003e(0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: axSpA, axial Spondyloarthritis; MSK = musculoskeletal, na, not applicable.\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7526871/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7526871/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eDespite increasing digitalization and the central role of non-pharmacological interventions in rheumatic diseases, no digital therapeutic (DTx) has yet been shown to meaningfully improve disease activity in rheumatology. Axia is a novel app-based DTx for axial spondyloarthritis (axSpA) that combines personalized exercise therapy, patient education, and disease management, supported by gamification elements to enhance long-term adherence. To evaluate its clinical efficacy, we conducted a 12-week nationwide, randomized, controlled interventional trial (RCT) involving 200 axSpA patients with stable pharmacotherapy. Patients were randomized (1:1) to either using Axia (intervention group) or standard of care (control group). Of the 200 axSpA patients enrolled, 186 participants (95 in the intervention group and 91 in the control group) completed the study. Compared to control, participants in the Axia intervention group demonstrated significant improvements in disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]; ANCOVA-estimated group difference: -1.508, p\u0026lt;0.001), functional status (Bath Ankylosing Spondylitis Functional Index [BASFI]; -1.139; p\u0026lt;0.001) and disease-specific quality of life (Ankylosing Spondylitis Quality of Life questionnaire [ASQoL]; -2.297; p\u0026lt;0.001), all exceeding minimal clinically important difference (MCID) thresholds. Furthermore, a significantly higher proportion of patients in the intervention group achieved an Assessment of Spondyloarthritis International Society (ASAS)20 response compared to the control group (51% vs. 9%; p\u0026lt;0.001), and the ASAS40 response rate was also markedly higher (23% vs. 3%; p\u0026lt;0.001). No concerning safety signals were observed. These findings mark the first large-scale RCT to demonstrate that a digital intervention can improve disease activity in inflammatory rheumatic disease, supporting its potential as a scalable, non-pharmacological care model.\u003c/p\u003e\n\u003cp\u003eDRKS-ID: DRKS00033783\u003c/p\u003e","manuscriptTitle":"The novel digital therapeutic Axia improves disease activity, functionality, and quality of life in axial spondyloarthritis patients: a randomized controlled trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-23 02:31:18","doi":"10.21203/rs.3.rs-7526871/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"267fd1f9-a6eb-4705-878c-e05de00ca33b","owner":[],"postedDate":"September 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":54629017,"name":"Health sciences/Medical research/Clinical trial design/Randomized controlled trials"},{"id":54629018,"name":"Health sciences/Health care/Therapeutics"}],"tags":[],"updatedAt":"2025-10-23T09:32:06+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-23 02:31:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7526871","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7526871","identity":"rs-7526871","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}