Long-term outcomes of relapsing polychondritis: A multicenter study

Long-term outcomes of relapsing polychondritis: A multicenter study | 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 Long-term outcomes of relapsing polychondritis: A multicenter study Mehdi Jafarpour, Seyedmostafa Seyedmardani, Alireza Khabbazi, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4320551/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 17 Jul, 2024 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Relapsing polychondritis (RPC) is a systemic immune mediated disease characterized by recurrent episodes of inflammation in various cartilage-rich areas. RPC may cause extensive tissue destruction and is associated with significant morbidity and mortality. In this multicenter study, we considered the remission status and long-term outcomes of RPC in patients who were followed-up in six referral rheumatology centers in Iran. Outcomes of disease was assessed by remission status and RPC induced damage. A total of 29 patients with RPC were examined for enrollment in the study, and 26 patients with a minimum follow-up period of 6 months were included in the RPC outcome analysis. Median time to control of symptoms and sustained remission were 5 and 23 weeks, respectively. Prednisolone was discontinued in 8 (30.8%) patients and medication-free remission was achieved in 7 (23.1%) patients. Regarding the disease course, 34.6% of patients had a relapsing-remitting course, 42.3% had a monophasic course, and 23.1% had an always-active course. Despite extensive treatment with immunosuppressive medications, RPC induced damage was developed in 21 (80.8%) patients. Ear deformity and osteoporosis were the most common RPC induced damage. Long-term remission and medications-free remission in RPC is accessible. However, RPC related damage occur in majority of patients. Biological sciences/Immunology Health sciences/Rheumatology relapsing polychondritis remission disease modifying antirheumatic drugs (DMARDs) relapse immunosuppressants Introduction Relapsing polychondritis (RPC) is a systemic immune mediated disease characterized by recurrent episodes of inflammation in various cartilage-rich areas, such as the ears, nose, joints and respiratory tract 1 . Although the exact cause of RPC is unknown, it is thought to be an autoimmune disorder, as circulating autoantibodies against collagens II, IX, XI, cartilage oligomeric matrix proteins, and matrilin-1 have been identified in these patients 2 . RPC is a rare disease, with an estimated prevalence of 3.5–4.5 cases per million people 2 . It can affect peoples of any age, but it most commonly presents in ages of 40 and 60, and both males and females can be affected equally 2,3 . RPC may cause extensive tissue destruction and is associated with significant morbidity and mortality 1,2 . Considering the relapsing remitting course of RPC, the goal of treatment in this disease is to control the inflammatory crisis to prevent further tissue damage and long-term suppression of immune-mediated pathogenic mechanisms to prevent disease recurrence 2,4 . Due to the rarity of the disease and lack of controlled studies, there are no evidence-based guidelines for the treatment of RPC. However, non-steroidal ant-inflammatory drugs (NSAIDs) and glucocorticoids (GCs) used for control of acute inflammation and conventional synthetic disease modifying antirheumatic drugs (csDMARDs) including azathioprine, methotrexate, cyclophosphamide, and cyclosporine and biologic DMARDs (bDMARDs) used for control of immune system activity with variable results 2,4 . Despite numerous case reports and case series on the clinical manifestations and treatments of RPC, there are few data on the long-term outcomes of RPC treatment. In this multicenter study, we considered the remission status and long-term outcomes of RPC. Methods Study population This retrospective multicenter study was conducted to investigate the long-term outcomes of RPC in patients who were followed-up from July 2014 to October 2023 in six referral rheumatology centers in Iran including, Tabriz, Mashhad, Urmia, Tehran, Kashan, and Isfahan universities of medical sciences. Patients were included in the study if (i) were older than 18 years at disease onset, (ii) met the McAdam's criteria 5 modified by Damian and Levine 6 for RPC, (iii) had at least 3 visits per year and (iv) had at least 6 months follow-up. Patients with insufficient data, irregular follow-up and loss to follow-up were excluded. The study protocol was approved by the ethics committee of Tabriz University of Medical Sciences (Ethical code: IR.TBZMED.REC.1402.294). Informed consent was obtained from all participants. This study was conducted in accordance with the Declaration of Helsinki. Data collection and outcome assessment The demographic, clinical, laboratory, therapies and outcomes data of the patients were obtained from their charts. The follow-up time was determined from the date of entering the cohort to the last visit. In case of incomplete data or loss to follow-up, we tried to obtain information through direct or telephone interviews. Remission in all patients was assessed by an expert rheumatologist. Outcomes of disease was assessed by remission status and RPC induced damage. Control of symptoms was defined as control of inflammatory symptoms (chondritis, arthritis, skin lesions, etc) with any dose of prednisolone and DMARDs for at least 4 weeks. Sustained remission was defined to control of inflammatory symptoms, prednisolone dose ≤ 7.5 mg/d for at least 12 weeks. DMARDs were permitted. Relapse of RPC was defined as ( 1 ) worsening or development of new RPC-related symptoms identified by physical examination or imaging studies and leading to treatment escalation or ( 2 ) an increase in C-reactive protein (CRP) and erythrocyte sedimentation rate from baseline levels, which is considered due to RPC activity and led to treatment intensification 7 . In patients with multiple remissions and relapses, the remission with the longest duration was used in the analysis of duration of remission. RPC induced damage was assessed using the relapsing polychondritis damage index (RPDAM) 8 . Statistical analysis Statistical analysis was performed using SPSS software version 16.0 (SPSS, Inc., USA). The normal distribution of data was assessed using the Kolmogorov–Smirnov test. Normally and non-normally distributed continuous variables were reported as mean ± standard deviation (SD) and median (25–75% interquartile range [IQR]), respectively. Categorical variables were reported as frequency and percentage. Results A total of 29 patients with RPC were examined for enrollment in the study, whose demographic, clinical and laboratory characteristics are shown in Table 1 . Finally, 26 patients with a minimum follow-up period of 6 months were included in the RPC outcome analysis (Table 2 ). Mean age of the participants at the time of diagnosis was 42.8 ± 15.3 years and female:male ratio was 1.6. The median duration of follow-up was 41 months (IQR: 19, 73). Auricular chondritis, nose chondritis, laryngeal chondritis, fever, arthralgia/arthritis, scleritis and uveitis were the most frequent clinical manifestations (Table 1 ). At least one auto-antibodies including perinuclear antineutrophilic cytoplasmic antibody (P-ANCA), cytoplasmic ANCA (C-ANCA), anti-nuclear antibody (ANA) and rheumatoid factor (RF) was positive in 17 (58.6%) patients (Table 1 ). Table 1 Demographic, clinical and paraclinical characteristics of included patients (n = 29) Demographic characteristics Age at the time of diagnosis, mean ± SD, years 42.8 ± 15.3 Female (%) 18 (62.1) Familial history of rheumatic disease (%) 4 (13.8) Smoking (%) 3 (10.3) Disease duration before diagnosis, median (IQR), weeks 22 (10.5, 64.0) Constitutional symptoms (%) 11 (37.9) Chondritis (%) Ear (%) Nose (%) Larynx (%) 29 (100) 25 (86.2) 16 (55.2) 12 (41.4) Hearing loss/vestibular dysfunction (%) 5 (17.2) Oral ulcer (%) 2 (6.9) Eye involvement (%) Scleritis (%) Uveitis (%) Keratitis (%) Episcleritis (%) Conjunctivitis (%) Optic neuritis (%) 11 (37.9) 4 (36.4) 4 (36.4) 2 (18.2) 1 (9.1) 1 (9.1) 1 (9.1) Arthralgia (%) 16 (55.2) Arthritis Monoarthritis (%) Oligoarthritis (%) Polyarthritis (%) 7 (24.1) 2 (28.6) 4 (57.1) 1 (14.3) Skin lesions (%) 2 (6.9) Renal involvement Proteinuria (%) Active urine (%) 4 (13.8) 3 (10.3) 3 (10.3) Overlap with other diseases (%) Systemic lupus erythematosus (%) ANCA associated vasculitis (%) Behcet’s disease (%) Rheumatoid arthritis (%) Autoimmune hepatitis (%) 6 (20.7) 1 (3.5) 1 (3.5) 1 (3.5) 1 (3.5) 1 (3.5) Laboratory parameters Leukocytosis (%) ESR, median (IQR), mm/h High CRP (%) ANCA-P (%) ANCA-C (%) ANA (%) RF (%) 4 (13.8) 35 (11, 72) 23 (79.3) 7 (24.1) 1 (3.5) 6 (20.7) 5 (17.2) SD, standard deviation; IQR, interquartile range; TNF, tumor necrosis factor; P-ANCA, perinuclear antineutrophilic cytoplasmic antibody; C-ANCA, cytoplasmic ANCA; ANA, anti-nuclear antibody; RF, rheumatoid factor Table 2 Patients’ medications and outcomes of treatment (n = 26) Duration of follow-up, median (IQR), months 41 (19, 73) Medications Prednisolone (%) Azathioprine (%) Methotrexate (%) Cyclophosphamide (%) Leflunomide (%) Mycophenolate Mofetil (%) TNF inhibitors (%) Dapson (%) Hydroxychloroquine (%) Colchicine (%) Rituximab (%) 25 (96.2) 14 (53.8) 13 (50.0) 5 (19.2) 4 (15.4) 4 (15.4) 4 (15.4) 3 (11.5) 2 (7.7) 2 (7.7) 1 (3.8) Adherence to therapy (%) 20 (76.9) Results of treatment Control of symptoms (%) Sustained remission (%) Resistant to therapy (%) 22 (84.6) 20 (76.9) 4 (15.4) Time to control of symptoms, median (IQR), weeks 5 ( 4 , 12 ) Time to sustained remission, median (IQR), weeks 23 (12, 49) Duration of remission, median (IQR), months 36.5 (12, 48) Disease course Relapsing remitting (%) Mono phasic (%) Always active (%) 9 (34.6) 11 (42.3) 6 (23.1) Initial prednisolone dose ( mg/d), median (IQR) Final prednisolone dose (mg/d), median (IQR) Prednisolone discontinuation (%) Flare of disease after prednisolone discontinuation (%) Duration of prednisolone free remission, median (IQR), months 30 (11, 30) 5 (0, 10) 8 (30.8) 2 (25) 45 (12, 58) Initial therapy Monotherapy with DMARDs (%) Combination of 2 DMARDs (%) Only prednisolone (%) 21 (80.8) 3 (11.5) 2 (7.7) Treatment during disease course Continuation of initial DMARDs (%) Changing of initial DMARDs because of inefficacy or intolerance (%) Adding other DMARDs (%) No DMARDs (%) 9 (34.6) 8 (30.8) 7 (26.9) 2 (7.7) Medications-free remission (%) 6 (23.1) Relapse of disease after DMARDs discontinuation (%) 3 (50) Time to medications-free remission, median (IQR), months 43.5 (16, 90) Duration of medications-free remission, median (IQR), months 32.5 (7.3, 57.7) Remission in last visit (%) 18 (69.2) Duration of remission in last visit, median (IQR), months 38 (14, 48) Treatment at the last visit Only prednisolone Prednisolone and DMARDs Only DMARDS No medications 1 (3.8) 16 (61.5) 4 (15.4) 5 (19.2) IQR, interquartile range; TNF, tumor necrosis factor; DMARDs, disease-modifying antirheumatic drugs All patients were treated with GCs and/or DMARDs. Prednisolone was the most commonly used medication (Table 2 ). Other frequently used medications were azathioprine (53.8%), methotrexate (50.0%), and cyclophosphamide (19.2%). As initial therapy, all but 2 patients were treated with DMARDs. Monotherapy with DMARDs was performed in 21 (80.8%) patients and combination therapy was performed in 3 (11.5%) patients. However, during the course of the disease, a second DMARD was added to the treatment regimen in 7 (26.9%) patients, and the first DMARD was changed to another DMARD in 8 (30.8%) patients. Treatment with GCs and DMARDs lead to control of symptoms in 84.6% of patients and sustained remission in 76.9% of patients. Median time to control of symptoms and sustained remission were 5 and 23 weeks, respectively (Table 2 , Fig. 1 ). In all patients who responded to treatment, the response occurred within 12 months of diagnosis and initiation of treatment (Fig. 1 ). Prednisolone was discontinued in 8 patients (30.8%) and medication-free remission was achieved in 7 (23.1%) patients. Regarding the disease course, 34.6% of patients had a relapsing-remitting course, 42.3% had a monophasic course, and 23.1% had an always-active course. Despite extensive treatment with immunosuppressive medications, RPC induced damage was developed in 21 (80.8%) patients (Table 3 ). Median (IQR) RPDAM was 1 (0.8, 2). Ear deformity and osteoporosis were the most common RPC induced damage (Table 3 ). Five years survival rate was 95.5% Table 3 Relapsing polychondritis induced damage in various organs (n = 26) Any damage (%) 21 (80.8) Ear deformity (%) 9 (34.6) Osteoporosis (%) 9 (34.6) Hearing loss (%) 5 (19.2) Saddle nose deformity (%) 4 (15.4) Stridor (%) 3 (11.5) Corneal damage (%) 1 (3.8) Sjogren’s syndrome (%) 1 (3.8) Deep vein thrombosis (%) 1 (3.8) Erosive/deforming arthritis (%) 1 (3.8) Avascular necrosis (%) 1 (3.8) RPDAM, median (IQR) 1 (0.8, 2) Severe infection needs hospitalization 2 (7.8) Surgery for disease complications (%) 2 (7.8) Mortality (%) 1 (3.8) RPDAM, relapsing polychondritis damage index; IQR, interquartile range Discussion Management of RPC poses significant challenges due to its rarity and the heterogeneity of symptoms and disease course. This study aimed to evaluate the outcomes and treatment patterns in a cohort of RPC patients, shedding light on the current understanding of this complex disease. The results of this study showed that RPC was diagnosed 22 weeks after the onset of symptoms and treatment with GCss and DMARDs resulted in symptom control and sustained remission in most patients (85% and 77%). Response to treatment occurred in majority of patients in 5 months and in all patients within 12 months. These results are encouraging, as achieving remission is a primary therapeutic goal in RPC to prevent further damage to cartilage structures. Medication-free remission was achieved in 23% of patients. However, relapse occurred in 25% of patients after discontinuation of prednisolone and in 50% of patients after discontinuation of DMARDs, suggesting the need for ongoing monitoring and management to prevent relapse. Comparing this study results with previous reports is difficult because of the differences in patients’ characteristics and outcome definitions and the lack of data about remission rate in most studies. However, the five years survival rate in our study (95.5%) was consistent with recent studies from other countries. In Shimizu et al. report DCs, csDMARDs and bDMARDs were used in 91, 60 and 14 percent of RPC patients 9 . They reported increase in the prescription of csDMARDs and bDMARDs in 2019 compared to 2009 and a decrease in RPC mortality from 22–3% during this time period 9 . Sangle et al. in a retrospective study reported a diagnosis delay of 55 weeks 10 . Combination therapy with prednisolone and DMARDs was performed in 97% of patients and 63% eventually required biological drugs 10 . However, mortality was 18% 10 . Recent evidences shows that improvements in diagnostic methods and treatment of RPC have led to earlier diagnosis and an increase in the 10-year survival rate from 55% in 1986 11 to 91% in 2016 12 . In a single center study from Japan diagnosis delay was 22 weeks 13 . Although 26% of patients experienced sustained remission, relapse occurred in the remaining 74% 13 . Higher CRP level and monotherapy with GCs was associated with relapse 13 . This study was a multicenter study that, to the best of our knowledge, focused for the first time on remission rates and medications-free remission in RPC. However, due to the small sample size, we were unable to analyze predictors of medication-free remission and damage. Conclusion Long-term remission and medications-free remission in RPC is accessible. However, RPC induced damage occur in majority of patients. Declarations Conflict of interest No conflict of interests was declared by authors. Contributions Conceptualization and designing the study: Mehdi Jafarpour and Alireza Khabbazi Data acquisition: Maryam Saemi, Maryam Sahebari, Seyedmostafa Seyedmardani, Mansour Salesi, Sarah Hosseinpoor, Tahereh Faezi, Kamal Esalatmanesh, Mehrzad Hajialilo, Sousan Kolahi, Zahra myrfeizi, Alireza Khabbazi Drafting the manuscript: Mehdi Jafarpour, Alireza Khabbazi and Maryam Saberivand Funding This study was founded by the Connective Tissue Diseases Research Center. Author Contribution Conceptualization and designing the study: M.J and A.K.Data acquisition: M.S, M.S, S.S, M.S, S.H, T.F, K.E, M.H, S.K, Z.M, A.K.Drafting the manuscript: M.J, A.K and M.S. Acknowledgement We thank all the participants of this study who contributed with us and Connective Tissue Diseases Research Center for supporting this study. Data Availability The data underlying this article will be shared on reasonable request to the corresponding author. References Lahmer, T. et al. Relapsing polychondritis: an autoimmune disease with many faces. Autoimmun. Rev. 9, 540–546 (2010). Borgia, F., Giuffrida, R., Guarneri, F., Cannavò, S.P. Relapsing Polychondritis: An Updated Review. Biomedicines 6, 84 (2018). Horváth, A. et al. A nationwide study of the epidemiology of relapsing polychondritis. Clin. Epidemiol. 8, 211–30 (2016). Arnaud, L., Mathian, A., Haroche, J., Gorochov, G., Amoura, Z. Pathogenesis of relapsing polychondritis: a 2013 update. Autoimmun. Rev. 13(2), 90–5 (2014). McAdam, L.P., O’Hanlan, M.A., Bluestone, R., Pearson, C.M. Relapsing polychondritis: prospective study of 23 patients and a review of the literature. Medicine. (Baltimore). 55, 193–215 (1976). Damiani, J.M., Levine, H.L. Relapsing polychondritis-report of ten cases. The. Laryngoscope. 89, 929–946 (1979). Yoshida, T.et al. Risk factors for the recurrence of relapsing polychondritis. Arthritis. Res. Ther. 24, 127 (2022). Mertz, P. et al. The relapsing polychondritis damage index (RPDAM): Development of a disease-specific damage score for relapsing polychondritis. Joint. Bone. Spine. 86, 363–368 (2019). Shimizu, J., Yamano, Y., Kawahata, K., Suzuki, N. Nationwide cross–sectional survey of patients with relapsing polychondritis in 2019 demonstrates reduction of airway involvement compared with that in 2009. Sci. Rep. 12, 465 (2022). Sangle, S.R. et al. Relapsing polychondritis - A single Centre study in the United Kingdom. Autoimmun Rev 22, 103352 (2023). Michet, C.J., McKenna, C.H., Luthra, H.S., O’Fallon, W.M. Relapsing polychondritis. Survival and predictive role of early disease manifestations. Ann. Intern. Med. 104, 74–8 (1986). Dion, J. et al. Relapsing polychondritis can be characterized by three different clinical phenotypes: analysis of a recent series of 142 patients. Arthritis. Rheumatol. 68, 2992–3001 (2016). Yoshida, T. et al. Risk factors for the recurrence of relapsing polychondritis. Arthritis. Res. Ther. 24, 127 (2022). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 17 Jul, 2024 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 16 May, 2024 Reviews received at journal 13 May, 2024 Reviews received at journal 05 May, 2024 Reviewers agreed at journal 04 May, 2024 Reviewers agreed at journal 04 May, 2024 Reviewers invited by journal 02 May, 2024 Editor assigned by journal 02 May, 2024 Editor invited by journal 02 May, 2024 Submission checks completed at journal 29 Apr, 2024 First submitted to journal 24 Apr, 2024 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. 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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-4320551","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":298805209,"identity":"f9c421ae-de91-4339-ba36-8220ba8abd1e","order_by":0,"name":"Mehdi Jafarpour","email":"","orcid":"","institution":"Tabriz University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mehdi","middleName":"","lastName":"Jafarpour","suffix":""},{"id":298805211,"identity":"f4292e88-b94c-4e51-bcf0-e587460c078a","order_by":1,"name":"Seyedmostafa Seyedmardani","email":"","orcid":"","institution":"Urmia University of 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17:16:29","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":773750,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4320551/v1/672508ae-2040-4644-b19a-417e47a1d4a7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":" Long-term outcomes of relapsing polychondritis: A multicenter study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRelapsing polychondritis (RPC) is a systemic immune mediated disease characterized by recurrent episodes of inflammation in various cartilage-rich areas, such as the ears, nose, joints and respiratory tract\u003csup\u003e1\u003c/sup\u003e. Although the exact cause of RPC is unknown, it is thought to be an autoimmune disorder, as circulating autoantibodies against collagens II, IX, XI, cartilage oligomeric matrix proteins, and matrilin-1 have been identified in these patients\u003csup\u003e2\u003c/sup\u003e. RPC is a rare disease, with an estimated prevalence of 3.5\u0026ndash;4.5 cases per million people\u003csup\u003e2\u003c/sup\u003e. It can affect peoples of any age, but it most commonly presents in ages of 40 and 60, and both males and females can be affected equally\u003csup\u003e2,3\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eRPC may cause extensive tissue destruction and is associated with significant morbidity and mortality\u003csup\u003e1,2\u003c/sup\u003e. Considering the relapsing remitting course of RPC, the goal of treatment in this disease is to control the inflammatory crisis to prevent further tissue damage and long-term suppression of immune-mediated pathogenic mechanisms to prevent disease recurrence\u003csup\u003e2,4\u003c/sup\u003e. Due to the rarity of the disease and lack of controlled studies, there are no evidence-based guidelines for the treatment of RPC. However, non-steroidal ant-inflammatory drugs (NSAIDs) and glucocorticoids (GCs) used for control of acute inflammation and conventional synthetic disease modifying antirheumatic drugs (csDMARDs) including azathioprine, methotrexate, cyclophosphamide, and cyclosporine and biologic DMARDs (bDMARDs) used for control of immune system activity with variable results\u003csup\u003e2,4\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDespite numerous case reports and case series on the clinical manifestations and treatments of RPC, there are few data on the long-term outcomes of RPC treatment. In this multicenter study, we considered the remission status and long-term outcomes of RPC.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003e This retrospective multicenter study was conducted to investigate the long-term outcomes of RPC in patients who were followed-up from July 2014 to October 2023 in six referral rheumatology centers in Iran including, Tabriz, Mashhad, Urmia, Tehran, Kashan, and Isfahan universities of medical sciences. Patients were included in the study if (i) were older than 18 years at disease onset, (ii) met the McAdam's criteria\u003csup\u003e5\u003c/sup\u003e modified by Damian and Levine\u003csup\u003e6\u003c/sup\u003e for RPC, (iii) had at least 3 visits per year and (iv) had at least 6 months follow-up. Patients with insufficient data, irregular follow-up and loss to follow-up were excluded. The study protocol was approved by the ethics committee of Tabriz University of Medical Sciences (Ethical code: IR.TBZMED.REC.1402.294). Informed consent was obtained from all participants. This study was conducted in accordance with the Declaration of Helsinki.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData collection and outcome assessment\u003c/h2\u003e \u003cp\u003e The demographic, clinical, laboratory, therapies and outcomes data of the patients were obtained from their charts. The follow-up time was determined from the date of entering the cohort to the last visit. In case of incomplete data or loss to follow-up, we tried to obtain information through direct or telephone interviews. Remission in all patients was assessed by an expert rheumatologist. Outcomes of disease was assessed by remission status and RPC induced damage. Control of symptoms was defined as control of inflammatory symptoms (chondritis, arthritis, skin lesions, etc) with any dose of prednisolone and DMARDs for at least 4 weeks. Sustained remission was defined to control of inflammatory symptoms, prednisolone dose\u0026thinsp;\u0026le;\u0026thinsp;7.5 mg/d for at least 12 weeks. DMARDs were permitted. Relapse of RPC was defined as (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) worsening or development of new RPC-related symptoms identified by physical examination or imaging studies and leading to treatment escalation or (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) an increase in C-reactive protein (CRP) and erythrocyte sedimentation rate from baseline levels, which is considered due to RPC activity and led to treatment intensification\u003csup\u003e7\u003c/sup\u003e. In patients with multiple remissions and relapses, the remission with the longest duration was used in the analysis of duration of remission. RPC induced damage was assessed using the relapsing polychondritis damage index (RPDAM)\u003csup\u003e8\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using SPSS software version 16.0 (SPSS, Inc., USA). The normal distribution of data was assessed using the Kolmogorov\u0026ndash;Smirnov test. Normally and non-normally distributed continuous variables were reported as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) and median (25\u0026ndash;75% interquartile range [IQR]), respectively. Categorical variables were reported as frequency and percentage.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 29 patients with RPC were examined for enrollment in the study, whose demographic, clinical and laboratory characteristics are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Finally, 26 patients with a minimum follow-up period of 6 months were included in the RPC outcome analysis (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Mean age of the participants at the time of diagnosis was 42.8\u0026thinsp;\u0026plusmn;\u0026thinsp;15.3 years and female:male ratio was 1.6. The median duration of follow-up was 41 months (IQR: 19, 73). Auricular chondritis, nose chondritis, laryngeal chondritis, fever, arthralgia/arthritis, scleritis and uveitis were the most frequent clinical manifestations (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). At least one auto-antibodies including perinuclear antineutrophilic cytoplasmic antibody (P-ANCA), cytoplasmic ANCA (C-ANCA), anti-nuclear antibody (ANA) and rheumatoid factor (RF) was positive in 17 (58.6%) patients (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic, clinical and paraclinical characteristics of included patients (n\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDemographic characteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at the time of diagnosis, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42.8\u0026thinsp;\u0026plusmn;\u0026thinsp;15.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (62.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFamilial history of rheumatic disease (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (13.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (10.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDisease duration before diagnosis, median (IQR), weeks\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (10.5, 64.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eConstitutional symptoms (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (37.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChondritis (%)\u003c/b\u003e\u003c/p\u003e \u003cp\u003eEar (%)\u003c/p\u003e \u003cp\u003eNose (%)\u003c/p\u003e \u003cp\u003eLarynx (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (100)\u003c/p\u003e \u003cp\u003e25 (86.2)\u003c/p\u003e \u003cp\u003e16 (55.2)\u003c/p\u003e \u003cp\u003e12 (41.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHearing loss/vestibular dysfunction (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (17.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOral ulcer (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEye involvement (%)\u003c/b\u003e\u003c/p\u003e \u003cp\u003eScleritis (%)\u003c/p\u003e \u003cp\u003eUveitis (%)\u003c/p\u003e \u003cp\u003eKeratitis (%)\u003c/p\u003e \u003cp\u003eEpiscleritis (%)\u003c/p\u003e \u003cp\u003eConjunctivitis (%)\u003c/p\u003e \u003cp\u003eOptic neuritis (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (37.9)\u003c/p\u003e \u003cp\u003e4 (36.4)\u003c/p\u003e \u003cp\u003e4 (36.4)\u003c/p\u003e \u003cp\u003e2 (18.2)\u003c/p\u003e \u003cp\u003e1 (9.1)\u003c/p\u003e \u003cp\u003e1 (9.1)\u003c/p\u003e \u003cp\u003e1 (9.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eArthralgia (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (55.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eArthritis\u003c/b\u003e\u003c/p\u003e \u003cp\u003eMonoarthritis (%)\u003c/p\u003e \u003cp\u003eOligoarthritis (%)\u003c/p\u003e \u003cp\u003ePolyarthritis (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (24.1)\u003c/p\u003e \u003cp\u003e2 (28.6)\u003c/p\u003e \u003cp\u003e4 (57.1)\u003c/p\u003e \u003cp\u003e1 (14.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSkin lesions (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRenal involvement\u003c/b\u003e\u003c/p\u003e \u003cp\u003eProteinuria (%)\u003c/p\u003e \u003cp\u003eActive urine (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (13.8)\u003c/p\u003e \u003cp\u003e3 (10.3)\u003c/p\u003e \u003cp\u003e3 (10.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOverlap with other diseases (%)\u003c/b\u003e\u003c/p\u003e \u003cp\u003eSystemic lupus erythematosus (%)\u003c/p\u003e \u003cp\u003eANCA associated vasculitis (%)\u003c/p\u003e \u003cp\u003eBehcet\u0026rsquo;s disease (%)\u003c/p\u003e \u003cp\u003eRheumatoid arthritis (%)\u003c/p\u003e \u003cp\u003eAutoimmune hepatitis (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (20.7)\u003c/p\u003e \u003cp\u003e1 (3.5)\u003c/p\u003e \u003cp\u003e1 (3.5)\u003c/p\u003e \u003cp\u003e1 (3.5)\u003c/p\u003e \u003cp\u003e1 (3.5)\u003c/p\u003e \u003cp\u003e1 (3.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLaboratory parameters\u003c/b\u003e\u003c/p\u003e \u003cp\u003eLeukocytosis (%)\u003c/p\u003e \u003cp\u003eESR, median (IQR), mm/h\u003c/p\u003e \u003cp\u003eHigh CRP (%)\u003c/p\u003e \u003cp\u003eANCA-P (%)\u003c/p\u003e \u003cp\u003eANCA-C (%)\u003c/p\u003e \u003cp\u003eANA (%)\u003c/p\u003e \u003cp\u003eRF (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (13.8)\u003c/p\u003e \u003cp\u003e35 (11, 72)\u003c/p\u003e \u003cp\u003e23 (79.3)\u003c/p\u003e \u003cp\u003e7 (24.1)\u003c/p\u003e \u003cp\u003e1 (3.5)\u003c/p\u003e \u003cp\u003e6 (20.7)\u003c/p\u003e \u003cp\u003e5 (17.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eSD, standard deviation; IQR, interquartile range; TNF, tumor necrosis factor; P-ANCA,\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eperinuclear antineutrophilic cytoplasmic antibody; C-ANCA, cytoplasmic ANCA; ANA,\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eanti-nuclear antibody; RF, rheumatoid factor\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePatients\u0026rsquo; medications and outcomes of treatment (n\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of follow-up, median (IQR), months\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (19, 73)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedications\u003c/p\u003e \u003cp\u003ePrednisolone (%)\u003c/p\u003e \u003cp\u003eAzathioprine (%)\u003c/p\u003e \u003cp\u003eMethotrexate (%)\u003c/p\u003e \u003cp\u003eCyclophosphamide (%)\u003c/p\u003e \u003cp\u003eLeflunomide (%)\u003c/p\u003e \u003cp\u003eMycophenolate Mofetil (%)\u003c/p\u003e \u003cp\u003eTNF inhibitors (%)\u003c/p\u003e \u003cp\u003eDapson (%)\u003c/p\u003e \u003cp\u003eHydroxychloroquine (%)\u003c/p\u003e \u003cp\u003eColchicine (%)\u003c/p\u003e \u003cp\u003eRituximab (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (96.2)\u003c/p\u003e \u003cp\u003e14 (53.8)\u003c/p\u003e \u003cp\u003e13 (50.0)\u003c/p\u003e \u003cp\u003e5 (19.2)\u003c/p\u003e \u003cp\u003e4 (15.4)\u003c/p\u003e \u003cp\u003e4 (15.4)\u003c/p\u003e \u003cp\u003e4 (15.4)\u003c/p\u003e \u003cp\u003e3 (11.5)\u003c/p\u003e \u003cp\u003e2 (7.7)\u003c/p\u003e \u003cp\u003e2 (7.7)\u003c/p\u003e \u003cp\u003e1 (3.8)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdherence to therapy (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (76.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eResults of treatment\u003c/b\u003e\u003c/p\u003e \u003cp\u003eControl of symptoms (%)\u003c/p\u003e \u003cp\u003eSustained remission (%)\u003c/p\u003e \u003cp\u003eResistant to therapy (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (84.6)\u003c/p\u003e \u003cp\u003e20 (76.9)\u003c/p\u003e \u003cp\u003e4 (15.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTime to control of symptoms, median (IQR), weeks\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTime to sustained remission, median (IQR), weeks\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (12, 49)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDuration of remission, median (IQR), months\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.5 (12, 48)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDisease course\u003c/b\u003e\u003c/p\u003e \u003cp\u003eRelapsing remitting (%)\u003c/p\u003e \u003cp\u003eMono phasic (%)\u003c/p\u003e \u003cp\u003eAlways active (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (34.6)\u003c/p\u003e \u003cp\u003e11 (42.3)\u003c/p\u003e \u003cp\u003e6 (23.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInitial prednisolone dose\u003c/b\u003e (\u003cb\u003emg/d), median (IQR)\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eFinal prednisolone dose (mg/d), median (IQR)\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003ePrednisolone discontinuation (%)\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eFlare of disease after prednisolone discontinuation (%)\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003eDuration of prednisolone free remission, median (IQR), months\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30 (11, 30)\u003c/p\u003e \u003cp\u003e5 (0, 10)\u003c/p\u003e \u003cp\u003e8 (30.8)\u003c/p\u003e \u003cp\u003e2 (25)\u003c/p\u003e \u003cp\u003e45 (12, 58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInitial therapy\u003c/b\u003e\u003c/p\u003e \u003cp\u003eMonotherapy with DMARDs (%)\u003c/p\u003e \u003cp\u003eCombination of 2 DMARDs (%)\u003c/p\u003e \u003cp\u003eOnly prednisolone (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (80.8)\u003c/p\u003e \u003cp\u003e3 (11.5)\u003c/p\u003e \u003cp\u003e2 (7.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTreatment during disease course\u003c/b\u003e\u003c/p\u003e \u003cp\u003eContinuation of initial DMARDs (%)\u003c/p\u003e \u003cp\u003eChanging of initial DMARDs because of inefficacy\u003c/p\u003e \u003cp\u003eor intolerance (%)\u003c/p\u003e \u003cp\u003eAdding other DMARDs (%)\u003c/p\u003e \u003cp\u003eNo DMARDs (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (34.6)\u003c/p\u003e \u003cp\u003e8 (30.8)\u003c/p\u003e \u003cp\u003e7 (26.9)\u003c/p\u003e \u003cp\u003e2 (7.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMedications-free remission (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (23.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRelapse of disease after DMARDs discontinuation (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTime to medications-free remission, median (IQR), months\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43.5 (16, 90)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDuration of medications-free remission, median (IQR), months\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.5 (7.3, 57.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRemission in last visit (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (69.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDuration of remission in last visit, median (IQR), months\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (14, 48)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTreatment at the last visit\u003c/b\u003e\u003c/p\u003e \u003cp\u003eOnly prednisolone\u003c/p\u003e \u003cp\u003ePrednisolone and DMARDs\u003c/p\u003e \u003cp\u003eOnly DMARDS\u003c/p\u003e \u003cp\u003eNo medications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.8)\u003c/p\u003e \u003cp\u003e16 (61.5)\u003c/p\u003e \u003cp\u003e4 (15.4)\u003c/p\u003e \u003cp\u003e5 (19.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eIQR, interquartile range; TNF, tumor necrosis factor; DMARDs, disease-modifying\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eantirheumatic drugs\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAll patients were treated with GCs and/or DMARDs. Prednisolone was the most commonly used medication (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Other frequently used medications were azathioprine (53.8%), methotrexate (50.0%), and cyclophosphamide (19.2%). As initial therapy, all but 2 patients were treated with DMARDs. Monotherapy with DMARDs was performed in 21 (80.8%) patients and combination therapy was performed in 3 (11.5%) patients. However, during the course of the disease, a second DMARD was added to the treatment regimen in 7 (26.9%) patients, and the first DMARD was changed to another DMARD in 8 (30.8%) patients. Treatment with GCs and DMARDs lead to control of symptoms in 84.6% of patients and sustained remission in 76.9% of patients. Median time to control of symptoms and sustained remission were 5 and 23 weeks, respectively (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In all patients who responded to treatment, the response occurred within 12 months of diagnosis and initiation of treatment (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Prednisolone was discontinued in 8 patients (30.8%) and medication-free remission was achieved in 7 (23.1%) patients. Regarding the disease course, 34.6% of patients had a relapsing-remitting course, 42.3% had a monophasic course, and 23.1% had an always-active course.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eDespite extensive treatment with immunosuppressive medications, RPC induced damage was developed in 21 (80.8%) patients (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Median (IQR) RPDAM was 1 (0.8, 2). Ear deformity and osteoporosis were the most common RPC induced damage (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Five years survival rate was 95.5%\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eRelapsing polychondritis induced damage in various organs (n\u0026thinsp;=\u0026thinsp;26)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAny damage (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (80.8)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEar deformity (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (34.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOsteoporosis (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (34.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHearing loss (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (19.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSaddle nose deformity (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (15.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStridor (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (11.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorneal damage (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (3.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSjogren\u0026rsquo;s syndrome (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (3.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeep vein thrombosis (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (3.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eErosive/deforming arthritis (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (3.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAvascular necrosis (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (3.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRPDAM, median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (0.8, 2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere infection needs hospitalization\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (7.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery for disease complications (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (7.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMortality (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (3.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eRPDAM, relapsing polychondritis damage index; IQR, interquartile range\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eManagement of RPC poses significant challenges due to its rarity and the heterogeneity of symptoms and disease course. This study aimed to evaluate the outcomes and treatment patterns in a cohort of RPC patients, shedding light on the current understanding of this complex disease. The results of this study showed that RPC was diagnosed 22 weeks after the onset of symptoms and treatment with GCss and DMARDs resulted in symptom control and sustained remission in most patients (85% and 77%). Response to treatment occurred in majority of patients in 5 months and in all patients within 12 months. These results are encouraging, as achieving remission is a primary therapeutic goal in RPC to prevent further damage to cartilage structures. Medication-free remission was achieved in 23% of patients. However, relapse occurred in 25% of patients after discontinuation of prednisolone and in 50% of patients after discontinuation of DMARDs, suggesting the need for ongoing monitoring and management to prevent relapse.\u003c/p\u003e \u003cp\u003eComparing this study results with previous reports is difficult because of the differences in patients\u0026rsquo; characteristics and outcome definitions and the lack of data about remission rate in most studies. However, the five years survival rate in our study (95.5%) was consistent with recent studies from other countries. In Shimizu et al. report DCs, csDMARDs and bDMARDs were used in 91, 60 and 14 percent of RPC patients\u003csup\u003e9\u003c/sup\u003e. They reported increase in the prescription of csDMARDs and bDMARDs in 2019 compared to 2009 and a decrease in RPC mortality from 22\u0026ndash;3% during this time period\u003csup\u003e9\u003c/sup\u003e. Sangle et al. in a retrospective study reported a diagnosis delay of 55 weeks\u003csup\u003e10\u003c/sup\u003e. Combination therapy with prednisolone and DMARDs was performed in 97% of patients and 63% eventually required biological drugs\u003csup\u003e10\u003c/sup\u003e. However, mortality was 18%\u003csup\u003e10\u003c/sup\u003e. Recent evidences shows that improvements in diagnostic methods and treatment of RPC have led to earlier diagnosis and an increase in the 10-year survival rate from 55% in 1986\u003csup\u003e11\u003c/sup\u003e to 91% in 2016\u003csup\u003e12\u003c/sup\u003e. In a single center study from Japan diagnosis delay was 22 weeks\u003csup\u003e13\u003c/sup\u003e. Although 26% of patients experienced sustained remission, relapse occurred in the remaining 74%\u003csup\u003e13\u003c/sup\u003e. Higher CRP level and monotherapy with GCs was associated with relapse\u003csup\u003e13\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThis study was a multicenter study that, to the best of our knowledge, focused for the first time on remission rates and medications-free remission in RPC. However, due to the small sample size, we were unable to analyze predictors of medication-free remission and damage.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eLong-term remission and medications-free remission in RPC is accessible. However, RPC induced damage occur in majority of patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eConflict of interest\u003c/h2\u003e \u003cp\u003eNo conflict of interests was declared by authors.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eContributions\u003c/h2\u003e \u003cp\u003eConceptualization and designing the study: Mehdi Jafarpour and Alireza Khabbazi\u003c/p\u003e \u003cp\u003eData acquisition: Maryam Saemi, Maryam Sahebari, Seyedmostafa Seyedmardani, Mansour Salesi, Sarah Hosseinpoor, Tahereh Faezi, Kamal Esalatmanesh, Mehrzad Hajialilo, Sousan Kolahi, Zahra myrfeizi, Alireza Khabbazi\u003c/p\u003e \u003cp\u003eDrafting the manuscript: Mehdi Jafarpour, Alireza Khabbazi and Maryam Saberivand\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThis study was founded by the Connective Tissue Diseases Research Center.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConceptualization and designing the study: M.J and A.K.Data acquisition: M.S, M.S, S.S, M.S, S.H, T.F, K.E, M.H, S.K, Z.M, A.K.Drafting the manuscript: M.J, A.K and M.S.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003e We thank all the participants of this study who contributed with us and Connective Tissue Diseases Research Center for supporting this study.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data underlying this article will be shared on reasonable request to the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLahmer, T. et al. Relapsing polychondritis: an autoimmune disease with many faces. \u003cem\u003eAutoimmun. Rev.\u003c/em\u003e 9, 540\u0026ndash;546 (2010).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBorgia, F., Giuffrida, R., Guarneri, F., Cannav\u0026ograve;, S.P. Relapsing Polychondritis: An Updated Review. Biomedicines 6, 84 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHorv\u0026aacute;th, A. et al. A nationwide study of the epidemiology of relapsing polychondritis. Clin. Epidemiol. 8, 211\u0026ndash;30 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArnaud, L., Mathian, A., Haroche, J., Gorochov, G., Amoura, Z. Pathogenesis of relapsing polychondritis: a 2013 update. Autoimmun. Rev. 13(2), 90\u0026ndash;5 (2014).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcAdam, L.P., O\u0026rsquo;Hanlan, M.A., Bluestone, R., Pearson, C.M. Relapsing polychondritis: prospective study of 23 patients and a review of the literature. Medicine. (Baltimore). 55, 193\u0026ndash;215 (1976).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDamiani, J.M., Levine, H.L. Relapsing polychondritis-report of ten cases. The. Laryngoscope. 89, 929\u0026ndash;946 (1979).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoshida, T.et al. Risk factors for the recurrence of relapsing polychondritis. Arthritis. Res. Ther. 24, 127 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMertz, P. et al. The relapsing polychondritis damage index (RPDAM): Development of a disease-specific damage score for relapsing polychondritis. Joint. Bone. Spine. 86, 363\u0026ndash;368 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShimizu, J., Yamano, Y., Kawahata, K., Suzuki, N. Nationwide cross\u0026ndash;sectional survey of patients with relapsing polychondritis in 2019 demonstrates reduction of airway involvement compared with that in 2009. Sci. Rep. 12, 465 (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSangle, S.R. et al. Relapsing polychondritis - A single Centre study in the United Kingdom. Autoimmun Rev 22, 103352 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMichet, C.J., McKenna, C.H., Luthra, H.S., O\u0026rsquo;Fallon, W.M. Relapsing polychondritis. Survival and predictive role of early disease manifestations. Ann. Intern. Med. 104, 74\u0026ndash;8 (1986).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDion, J. et al. Relapsing polychondritis can be characterized by three different clinical phenotypes: analysis of a recent series of 142 patients. \u003cem\u003eArthritis. Rheumatol.\u003c/em\u003e 68, 2992\u0026ndash;3001 (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoshida, T. et al. Risk factors for the recurrence of relapsing polychondritis. Arthritis. Res. Ther. 24, 127 (2022).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"relapsing polychondritis, remission, disease modifying antirheumatic drugs (DMARDs), relapse, immunosuppressants","lastPublishedDoi":"10.21203/rs.3.rs-4320551/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4320551/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eRelapsing polychondritis (RPC) is a systemic immune mediated disease characterized by recurrent episodes of inflammation in various cartilage-rich areas. RPC may cause extensive tissue destruction and is associated with significant morbidity and mortality. In this multicenter study, we considered the remission status and long-term outcomes of RPC in patients who were followed-up in six referral rheumatology centers in Iran. Outcomes of disease was assessed by remission status and RPC induced damage. A total of 29 patients with RPC were examined for enrollment in the study, and 26 patients with a minimum follow-up period of 6 months were included in the RPC outcome analysis. Median time to control of symptoms and sustained remission were 5 and 23 weeks, respectively. Prednisolone was discontinued in 8 (30.8%) patients and medication-free remission was achieved in 7 (23.1%) patients. Regarding the disease course, 34.6% of patients had a relapsing-remitting course, 42.3% had a monophasic course, and 23.1% had an always-active course. Despite extensive treatment with immunosuppressive medications, RPC induced damage was developed in 21 (80.8%) patients. Ear deformity and osteoporosis were the most common RPC induced damage. Long-term remission and medications-free remission in RPC is accessible. However, RPC related damage occur in majority of patients.\u003c/p\u003e","manuscriptTitle":" Long-term outcomes of relapsing polychondritis: A multicenter study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-07 20:29:23","doi":"10.21203/rs.3.rs-4320551/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-05-16T15:32:21+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-13T23:13:15+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-05T05:07:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"76715841953561039748602068241347720661","date":"2024-05-05T03:46:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"141666061959362638607618038077758293414","date":"2024-05-05T01:33:13+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-05-03T00:33:55+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-03T00:07:58+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-05-02T10:45:20+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-30T03:28:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-04-24T22:55:26+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0c6e6a3c-cac1-45bc-a3ca-1dbebaffab41","owner":[],"postedDate":"May 7th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":31524196,"name":"Biological sciences/Immunology"},{"id":31524197,"name":"Health sciences/Rheumatology"}],"tags":[],"updatedAt":"2024-08-01T16:16:11+00:00","versionOfRecord":{"articleIdentity":"rs-4320551","link":"https://doi.org/10.1038/s41598-024-67530-8","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2024-07-17 16:05:05","publishedOnDateReadable":"July 17th, 2024"},"versionCreatedAt":"2024-05-07 20:29:23","video":"","vorDoi":"10.1038/s41598-024-67530-8","vorDoiUrl":"https://doi.org/10.1038/s41598-024-67530-8","workflowStages":[]},"version":"v1","identity":"rs-4320551","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4320551","identity":"rs-4320551","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}