Disparities in diagnosis and management of chronic overlapping pain conditions in an observational study of medicare beneficiaries.

This cohort study used a 20% Medicare sample with fee-for-service enrollment, claims, and Part D data from 2018 to 2020. The group of beneficiaries included those with 9 or more months of Medicare parts A, B, and D for each of the years from 2018 to 2020. Beneficiaries with dual Medicare/Medicaid coverage and with no HMO plans were eligible for inclusion. Beneficiaries with end-stage renal disease were excluded. Enrollment data included monthly enrollment in Medicare Parts A, B, and D, and dual eligibility for Medicare/Medicaid. Part D event data included prescription drug fills with generic name, drug dose, date of service, and days’s supply. Morphine milligram equivalent was calculated using standard conversion ratios. 16 For medication related outcomes, 2018 was used as a washout period and 2020 was used for the follow-up period. Beneficiaries who were 66 years of age or older in 2019 were used to form the primary study group. Pain diagnoses of interest included: fibromyalgia, irritable bowel syndrome, interstitial cystitis, chronic prostatitis, vulvodynia, migraine, chronic tension-type headache, temporomandibular disorder, chronic low back pain, chronic fatigue syndrome, and endometriosis. Validated ICD-10 codes for these conditions were used to identify patients with a pain diagnosis. 9 Pain medication classes and specific medications of interest were those directed at the underlying pain mechanisms and included: tricyclic antidepressants [TCAs] (nortriptyline, amitriptyline, desipramine, imipramine, doxepin, amoxapine, protriptyline, trimipramine), serotonin-norepinephrine reuptake inhibitors [SNRIs] (duloxetine, venlafaxine, milnacipran), gabapentinoids (gabapentin, pregabalin), non-steroidal anti-inflammatory drugs [NSAIDs] (celecoxib, ibuprofen, naproxen, meloxicam, diclofenac, fenoprofen, indomethacin, ketorolac), cyclobenzaprine, divalproex/valproate, topiramate, beta blockers (propranolol, atenolol, metoprolol), and opioids (hydrocodone (with or without acetaminophen), oxycodone (with or without acetaminophen), morphine, hydromorphone, fentanyl, microgram buprenorphine, methadone, tramadol, and tapentadol). Only buprenorphine microgram products were included to avoid including buprenorphine products being used as medication for opioid use disorder rather than pain. Over-the-counter medications were not included in the dataset. The primary endpoint of the study was the prevalence of COPC diagnosis in Medicare beneficiaries with at least one COPC diagnosis in the 20% sample from 2018 to 2019. Secondary endpoints included rates of each diagnosis, differences in diagnosis by demographics, COPC-targeted medication and opioid use, and differences in medication use by demographics. For the diagnosis related secondary endpoints, only beneficiaries with a new, incident pain diagnosis in the study period were included (i.e., pain diagnosis in 2019 but no pain diagnosis in 2018). For the medication related secondary endpoints, only the beneficiaries with a new, incident pain diagnosis and no COPC-targeted medication prior to pain diagnosis were included. A beneficiary was considered to have received a COPC-targeted medication if they received a new prescription within 60 days after the first COPC diagnosis for which there was a diagnosis:medication match. 17 – 27 Only the first pain medication prescription was evaluated for this definition. Polypharmacy, was defined as receipt of 5 or more medications, was determined using the total number of unique prescriptions received within this same timeframe. To ensure these medications were being used for these diagnoses, for medication-related outcomes, only patients with a new, incident pain diagnosis were considered for the analysis. A new pain diagnosis was defined as a beneficiary that had no pain diagnosis or pain-related medication in 2018, but had a pain-diagnosis in 2019. The medication-related outcomes were limited to 2019 plus up to 60 days into 2020 to avoid any potential impacts of the pandemic on prescription claims. The initial analysis of the data was based on descriptive statistics, including counts/percentages and median (iqr, interquartile ranges). To analyze the outcomes, we used multivariable logistic regressions using covariates age, gender, race, polypharmacy, and comorbidity index adjusting with covariates. In addition to this, for our COPC-targeted medication logistic regressions, we included IPTW (inverse probability of treatment weighting) propensity score weights along with the multivariable adjustments to ensure double-robustness in controlling for selection bias in this retrospective study. We included the individual pain diagnoses and age in generating the weights for the four race “treatment” groups in the final logistic regressions. We used a metric of standardized mean differences of <0.1 to assess pairwise race group balance. IPTW weights were successful in reducing sample selection bias in our sample. All standardized mean differences in the eleven pain diagnoses and age were successfully reduced to less than 0.1. Unique prescription counts were analyzed using one-way ANOVA. All statistical analyses were performed in R, version 4.4.1. 28 The IPTW propensity score analysis was conducted using the “twang” package 29 and the weighted regressions were done with the “survey” package. 30 The Institutional Review Board of the University of Michigan deemed this study to be exempt. Patients and the public were not involved in the research given the nature of Medicare data requirements.

Among the 2,573,165 beneficiaries included in the study, 273,996 (10.6%) carried at least one COPC diagnosis during the study years ( Table 1 ). Females (61.5% vs. 38.5% males) and white patients (86.7% vs. 6.1% Black and 1.8% Asian) comprised the majority of the overall sample. Nearly the entire sample had one (92.6%) or two (6.7%) COPC diagnoses. The most predominant COPC diagnosis was chronic low back pain (71.6%), followed by irritable bowel syndrome (9.1%), fibromyalgia (8.2%), migraine (7.7%), and chronic fatigue syndrome (6.8%). The remaining diagnoses were found in less than 2% of the sample ( Table 1 ). Those with a COPC, compared to the entire population, were more likely to be female (68.4% vs. 61.5%), white (88% vs. 86.7%), and have a higher Elixhauser (van Walraven) Comorbidity Index (3.0 vs. 2.0). Compared to their white counterparts, Black (odds ratio [OR], 0.89 [95% CI, 0.88–0.91]) and Asian (OR, 0.68 [95% CI, 0.66–0.71]) beneficiaries were less likely to have a COPC diagnosis. Male beneficiaries (OR, 0.69 [95% CI, 0.68–0.69])) were less likely than female beneficiaries to have a new, incident COPC diagnosis, while increasing Elixhauser scores were associated with a COPC diagnosis (OR, 1.03 [95% CI, 1.03–1.03]). Of the beneficiaries with a COPC diagnosis in the sample (n=273,996), 11.4% (n=31,281) had a new, incident diagnosis within the dataset without having a diagnosis (or treatment) in the prior year ( Table 1 ). The most predominant COPC in the new, incident diagnosis beneficiaries was chronic low back pain (85.7%), followed by migraine (4.5%), chronic fatigue syndrome (3.0%), and fibromyalgia (2.6%). The remaining diagnoses were found in less than 2% of the sample. Black and Asian beneficiaries had higher rates of chronic low back pain, chronic tension type headache, and temporomandibular disorder diagnoses than their White counterparts, but lower rates for every other diagnosis ( Table 2 ). For beneficiaries with a new, incident COPC diagnosis, 24.1% (n=7541) received a COPC-targeted medication, while 29.5% (n=9235) received an opioid during a 60-day window following the service date of the COPC diagnosis. Of the beneficiaries who received a COPC-targeted medication ( Table 3 ), the majority were women (64.1%) and white (85.0%). A greater proportion of beneficiaries received opioids than COPC-targeted medications for every diagnosis except temporomandibular disorder and vulvodynia. Using IPTWs, Black (OR, 1.13 [95% CI, 1.02–1.26]), and Asian (OR, 1.32 [95% CI, 1.06–1.63]) beneficiaries were more likely to receive a COPC-targeted medication. Polypharmacy was also associated with COPC-targeted treatment (OR, 1.66 [95% CI, 1.44,1.9]). Black (OR, 1.12 [95% CI, 1.01–1.25]) beneficiaries were more likely to receive opioids, while Asian (OR, 0.66 [95% CI, 0.52–0.85]) beneficiaries were less likely to receive opioids. Polypharmacy had a strong association with opioid use (OR, 3.66 [95% CI, 3.15,4.24]). The median morphine equivalent after diagnosis was 20 mg [iqr=0.0,40.0]. The mean (standard deviation) number of unique prescriptions were: All 8.00 (4.38), White 8.01 (4.35), Black 8.26 (4.53), and Asian 7.80 (4.71) (p=0.001). For beneficiaries that received a COPC-targeted medication, the most commonly used classes of medications were NSAIDs (79.7%), SNRIs (11.5%), gabapentinoids (4.2%), and TCAs (2.9%). Black beneficiaries had higher prescription rates for NSAIDs, opioids, gabapentinoids, and cyclobenzaprine than White beneficiaries. Asian beneficiaries had higher prescription rates for NSAIDs and gabapentinoids than White beneficiaries. White beneficiaries had higher rates of SNRIs, TCAs, other anticonvulsants, or no prescriptions ( Table 4 ).

In this nationally representative cohort study, we found that one in ten older adults with Medicare fee-for-service and Part D coverage had a COPC, with chronic low back pain being the most common condition. Significant differences in the demographics of beneficiaries with a COPC were noted with Black and Asian beneficiaries being less likely to have a COPC diagnosis. Differences in treatment by race also persisted, with Black beneficiaries being more likely to receive COPC-targeted medications and opioids while Asian beneficiaries were more likely to receive COPC-targeted medications and less likely to receive opioids. These findings highlight the gaps in diagnosis and management of COPCs in older adults. Limited data exist on the prevalence of COPCs in the general population. 6 , 7 COPCs, by nature, are diagnoses of exposure given that age is a risk factor for COPC development and that these conditions can accumulate. 31 Although peak prevalence is seen in younger patients, the study of older adults is important given the complexity of the older patient with respect to medication use. We found that one in ten older adults has a COPC, which is an important finding in and of itself. However, because COPCs are managed mostly by centrally acting medications, the complexity of management in this population cannot be understated. Every medication available to support older adults with a COPC is on the Beers Criteria, which is a list of potentially harmful medications for older adults where there is often a risk:benefit imbalance, and puts these patients at risk of poor medication-related outcomes. 32 Therefore, it is unsurprising that only one in four older adults with a COPC receive mechanistically appropriate medication. We also found that opioid use is prevalent in this population, despite literature that supports that opioids worsen patient related outcomes for those with a COPC diagnosis. 14 , 15 An additional finding in this study was that polypharmacy had strong associations with opioid prescriptions, particularly compared to COPC-targeted prescriptions. The literature has previously reported that opioid use in older adults is associated with polypharmacy. 33 Data reporting disparities in the diagnosis and management of chronic pain are well known and we add to that literature with our findings. Black and Asian beneficiaries are less likely to receive a COPC diagnosis compared to their white counterparts, potentially due to systemic barriers such as racial stereotyping, implicit biases, and limited healthcare access. 13 While Black beneficiaries were more likely to receive a COPC-targeted medication, this is likely driven by high rates of NSAID prescriptions (24.5% of Black beneficiaries received an NSAID). Proportionally, more Black beneficiaries received NSAIDs, cyclobenzaprine, and gabapentinoids. This likely reflects high rate of chronic low back pain diagnosis in Black beneficiaries (80.3%) in the sample. This data aligns with previous literature that shows Black patients have higher rates of non-opioid prescriptions. 34 Moreover, racial minorities may face potential barriers such as financial constraints, language barriers, and living in areas with limited healthcare resources, which can contribute to the delay or absence of receiving a COPC diagnosis. Among those diagnosed, Black beneficiaries were more likely to receive opioids despite known worsened outcomes with their use in COPCs. 14 , 15 The majority of empirical evidence demonstrates that Black patients are less likely to be prescribed opioids 35 or to be prescribed significantly lower doses than their white counterparts, 36 a trend that may reflect biased scrutiny of opioid use in Black patients despite literature that supports higher misuse rates among white populations. 13 While our results are incongruent with much of the literature, they may reflect decreasing use of opioids as their harms have become more widely known. 37 ; this decrease in opioid prescribing has been disproportionately in white patients, with opioid prescribing levels staying stable from 2007 to 2014 for patients belonging to racial and ethnic minority groups but decreasing for white patients. 38 Aside from adverse outcomes directly related to opioid use, the receipt of opioids influences utilization of other therapies: prior opioid prescriptions predicted non-participation in physical therapy for low back pain. 39 and in another large cohort, use of non-opioids was associated with greater utilization of exercise and manual therapy. 40 The harm related to increased utilization of opioids for COPCs in Black older adults is thus two-fold. Not only are Black beneficiaries being exposed at a disproportionate rate to therapies that have known adverse effects and little to zero benefit for COPCs, but receipt of opioids may also adversely affect their utilization of non-pharmacological therapies that are safer and effective in COPCs. 41 This was an observational study using secondary data, so we recognize the inherent limitations in the approach, including that we examined associations, not causations or reasons underlying the disparities identified. Given the dataset, we were unable to report on prescriber characteristics as well. We reiterate, however, that our goal was to provide an estimate of the proportion of beneficiaries with a COPC and to begin the discussion of disparities within these diagnoses. We also recognize the limitation in the definition of COPC-targeted medications in that it is clear that the mechanisms of the medications do not match exactly the pathophysiologic mechanism of pain, but they are as close as possible given the current availability of medication mechanisms and are guideline supported. The proportion of beneficiaries with more than one COPC is lower than reported in other data. 42 , but is still present in this sample. This underrepresentation of multiple COPCs is likely artefact of using Medicare data. We also recognize the limitation on generalizability to the younger population or those with private insurance given the use of Medicare data; however, this study provides important insights that could be translated to those populations in future studies.

Approximately one in every ten older adults carries a COPC diagnosis. We identified significant differences in the proportion of beneficiaries with a COPC by race, noting Black and Asians are less likely to have a diagnosis. Only one in four patients filled a prescription for a COPC-targeted medication within 60 days of diagnosis, while nearly one in three filled an opioid prescription. Asian and Black patients were more likely to receive a COPC-targeted medication, while Black patients were more likely to receive an opioid, despite their known ineffectiveness and harms in COPCs. Given the risks of medication use in older adults, the careful use of COPC-targeted medications and the reduction in opioid use needs to improve. Efforts to reduce disparities to diagnose and manage COPCs among Medicare Part D beneficiaries is critical.

In 2011, the Institute of Medicine (IOM) reported that more than 100 million Americans suffer from chronic pain, primarily based on self-reported data from 2008. 1 , 2 The original study, while informative, did not provide information regarding pain characterization or management. 2 More than 15 years later, the IOM reported that some chronic pain conditions appeared to coexist. 1 However, little progress has been made in the research of chronic pain. 3 While we have new definitions of pain 4 , including a third descriptor known as nociplastic pain 5 , most studies in chronic pain conditions are undertaken in isolation, do not delineate etiology, and focus on quality of life. 3 , 6 , 7 What is known is that there are a set of pain diagnoses that commonly co-occur, and we now refer to them as “chronic overlapping pain conditions”, or COPCs, which fit within the definition of nociplastic pain. 8 Nociplastic pain is defined as “pain that arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain”. 4 , 5 The set of COPC diagnoses that fall within this category include: fibromyalgia, chronic low back pain, temporomandibular disorder, irritable bowel syndrome, vulvodynia, chronic fatigue syndrome, endometriosis, interstitial cystitis, chronic prostatitis, chronic tension type headache, and migraines. 6 These conditions, largely managed by individual medical specialties, were studied in siloes until sets of validated International Classification Codes (ICD) were established. 9 , 10 Given the recency of these validated code sets, there is opportunity to understand the prevalence of COPC and its treatment using administrative data and also explore whether disparities exist. In a cross-sectional, registry-based study of participants with chronic low back pain, disparities in pain control and patient functioning were noted for Black patients. 11 Disparities in pain diagnosis and management have existed for decades and traverse all acuities of pain (e.g., acute vs. chronic) and special populations (e.g., pediatric). 12 Disparities persist into treatment, including being offered certain medications, namely opioids. 13 While some pain conditions are responsive to opioids, COPCs are not and may in fact be worsened by the use of opioids. 14 , 15 The management of COPCs should be focused on matching, as closely as possible, the pathophysiological pain mechanisms with the mechanisms of a medication, also known as mechanistic-based pain therapy (MBPT), or COPC-targeted medications. 7 The intersection of COPCs, diagnosis and management (inclusive of COPC-targeted medications and opioids), and disparities has not been explored. We hypothesized that disparities seen in other pain syndromes would persist in those with COPCs. In this cohort study, we use Medicare data from 2018–2020 to characterize the rate of COPC diagnoses among older adults; examine the differences in diagnosis by race; characterize use of COPC-targeted medications and opioids; and evaluate the differences in treatment of these COPCs by race.