Abstract
Objective The aim of our study was to compare dispensation of rheumatic medications between older male and female patients with early rheumatoid arthritis (RA) and psoriatic arthritis (PsA).
Methods This retrospective cohort study was performed using health administrative data from Ontario, Canada (years 2010-2017), on patients with incident RA and PsA, who were aged ≥ 66 years at the time of diagnosis. Yearly dispensation of rheumatic drugs was compared between older male and female patients for 3 years after diagnosis using multivariable regression models, after adjusting for confounders. The groups of drugs included in the analysis were disease-modifying antirheumatic drugs (DMARDs) classified as conventional synthetic DMARDs (csDMARDs) and advanced therapy (biologic DMARDs and targeted synthetic DMARDs), nonsteroidal antiinflammatory drugs (NSAIDs), opioids, and oral corticosteroids. Results were reported as odds ratios (ORs) with 95% CIs.
Results We analyzed 13,613 patients (64% female) with RA and 1116 patients (57% female) with PsA. Female patients with RA were more likely to receive opioids (OR 1.39, 95% CI 1.22-1.58 to OR 1.51, 95% CI 1.32-1.72) and NSAIDs (OR 1.14, 95% CI 1.04-1.25 to OR 1.16, 95% CI 1.04-1.30). Dispensation of DMARDs showed no sex difference in either group. Subgroup analyses showed more intense use of advanced therapy in the RA cohort and of csDMARDs in the PsA cohort when patient and physician sex was concordant.
Conclusion This study did not identify any sex difference in the use of DMARDs among older patients with RA and PsA. The reasons for the higher use of opioids and NSAIDs among female patients with RA warrant further research.
- disease-modifying antirheumatic drugs
- pain medications
- psoriatic arthritis
- rheumatoid arthritis
- sex differences
Early initiation of disease-modifying antirheumatic drugs (DMARDs) is the cornerstone of therapy in both rheumatoid arthritis (RA) and psoriatic arthritis (PsA), leading to improved disease outcomes.1,2 Various aspects of these inflammatory forms of arthritis are associated with the sex of the patient. For example, male patients have worse structural damage and more severe psoriasis, whereas female patients have worse pain, fatigue, and respond poorly to treatment.3,4 Sex differences in outcomes could result in part from disparities in prescription patterns.
Most studies investigating sex differences in prescription patterns have been conducted in patients with RA taking DMARDs,5-10 leaving gaps in knowledge regarding other inflammatory arthritis (IA) and other rheumatic medications. Older patients tend to have higher risk for adverse events and a higher burden of comorbidities, which often limit therapeutic options. Moreover, prescribing practices vary between older men and women due to biological issues and sociocultural factors.11 Investigating prescription patterns in patients with IA of this age group could thus highlight important sex differences.
We therefore aimed to compare drug dispensation patterns between older male and female patients with IA within 3 years of diagnosis. Identifying sex-related disparities in drug dispensation could identify barriers to equitable care and direct efforts to optimize patient management.
METHODS
Setting and population. We performed a population-based, retrospective cohort study among older residents of Ontario, Canada, using health administrative data.
Using validated case definitions (Supplementary Table S1, available with the online version of this article), we assembled 2 mutually exclusive cohorts of patients with incident RA12 and PsA13 between 2010 and 2017. The study population comprised Ontario residents aged ≥ 66 years at index date (to allow 1 year for prescription updates), with valid health insurance for at least 5 years and diagnosed between April 1, 2010, and March 31, 2017. The date of diagnosis (index date) was the date of the patient’s first diagnosis code as determined by a specialist. Patients were followed for up to 3 years following the index date, death, or move out of province (whichever came first). Data sources and methods for cohort creation can be found in Supplementary Tables S1 and S2.14 The datasets (Supplementary Table S1) were linked using unique encoded identifiers and analyzed at ICES (www.ices.on.ca).
Use of the data in this project is authorized under section 45 of Ontario’s Personal Health Information Protection Act and does not require review by a research ethics board.
Exposure. Sex was the primary predictor of the study. Baseline variables and potential explanatory variables included age, location of residence, socioeconomic status (SES), marginalization, comorbidities (both individual and as Aggregated Diagnosis Groups [ADG] categories using the Johns Hopkins Adjusted Clinical Groups [ACG] System V.10),15 and access to rheumatologists in terms of regional density of rheumatologists and remote distance to rheumatologist (Supplementary Tables S3 and S4, available with the online version of this article).14
Study outcome. The study outcome was dispensation of rheumatic medications. All Ontarians receive universal drug coverage after 65 years of age under the Ontario Drug Benefit program. Dispensation of at least 1 prescription for the following drugs was assessed yearly for 3 years after diagnosis: conventional synthetic (cs)DMARDs and advanced therapy, including biologic (b) and targeted synthetic (ts)DMARDs; at least 90 days’ supply of nonsteroidal antiinflammatory drugs (NSAIDs) and opioids; and 30 days’ supply of oral corticosteroids (CS) (complete list of medications in Supplementary Table S5, available with the online version of this article).
Statistical analysis. The association between sex and dispensation of each drug category was analyzed using multivariable logistic regression models, adjusting for age, area of residence, SES, ADG categories of patients, and regional density of rheumatologists. Results were reported as odds ratios (OR) with 95% CIs. Separate models were constructed for RA and PsA. Prespecified subgroup analyses were conducted by area of residence (rural vs urban), SES, and sex of diagnosing specialist. Complete case analysis was employed.
RESULTS
A total of 13,613 patients with RA (64% female), and 1116 patients with PsA (57% female) were analyzed. Sociodemographic characteristics and comorbidities at the time of diagnosis are presented in Table 1. Burden of comorbidities was higher in females (more females in 10+ ADG categories). Osteoporosis was more common in female patients, whereas cardiovascular disease and cancer were more common in male patients in both cohorts.
Sociodemographic characteristics of older patients with inflammatory arthritis at the time of diagnosis, by patient sex.
Table 2 shows dispensation of medications by sex. Proportions of patients dispensed csDMARDs (79% in RA, 67% in PsA), NSAIDs (18-20% in RA, 25-27% in PsA) and oral CS (37-44% in RA, 13-14% in PsA) were highest in the first year after diagnosis and gradually decreased over time, whereas prescription of advanced therapy was lowest in the year after diagnosis (2.5% in RA, 7-8% in PsA) and gradually increased over time. Opioid dispensation remained relatively stable (7-11% in RA, 8-12% in PsA).
Dispensation of rheumatic medications in older patients with inflammatory arthritis, by patient sex.
Multivariable regression analysis showed that female patients with RA were more likely to receive opioids (OR 1.39, 95% CI 1.22-1.58 to OR 1.51, 95% CI 1.32-1.72) and NSAIDs (OR 1.14, 95% CI 1.04-1.25 to OR 1.16, 95% CI 1.04-1.30) during the 3 years after diagnosis, and advanced therapy in the third year after diagnosis (OR 1.23, 95% CI 1.05-1.45; Table 2). On the other hand, male patients with RA were more likely to receive oral CS (OR 0.73, 95% CI 0.68-0.79) immediately after diagnosis.
Subgroup analyses showed effect modification by sex of diagnosing specialist in both cohorts (Table 3). Female patients with RA were more likely to receive NSAIDs when diagnosed by male specialists, and advanced therapy when diagnosed by female specialists. In the PsA cohort, male patients diagnosed by male specialists were more likely to receive csDMARDs. Remaining subgroup analyses did not show effect modification by sex.
Dispensation patterns of rheumatic medications in older patients with inflammatory arthritis, odds ratios (ORs) for prescriptions in female patients compared to males, stratified by sex of the diagnosing specialists.
DISCUSSION
We describe sex differences in the dispensation of rheumatic drugs in older patients with RA and PsA. The most notable finding was the higher likelihood of female patients with RA to receive pain control medications after diagnosis. Sex of the diagnosing specialist influenced drug dispensation, with patient-physician sex concordance associated with more intense DMARD therapy.
Previous studies on sex differences in DMARD prescriptions in RA report conflicting results, likely attributed to differences in the study population in terms of demographics (age) and disease characteristics (prevalent vs incident cohorts). Higher use of csDMARDs in females have been reported,7,9 whereas Slim et al found no sex differences in DMARD prescriptions.10 Our study findings conform to the latter. Again, both higher6 and lower8 likelihood for advanced therapy in males with RA have been reported. Our study found that female patients with RA were more likely to receive advanced therapy in the third year after diagnosis, but no sex differences were observed in the first 2 years. Recent studies from the Netherlands and Germany reported no sex differences in treatment regimens of patients with PsA.16,17 The lack of sex differences in the dispensation of these medications, especially advanced therapy, is reassuring, even though the generalizability may be limited due to our older population. Of note, the presence of multiple comorbidities, as observed in our study, may limit options for DMARDs in older patients.
Dispensations of opioids were more common in female compared to male patients in both cohorts. Our findings align with those of a recent German study, where female patients with PsA were more likely to be prescribed analgesics and opioids compared to male patients.17 The proportion of patients using opioids was much lower in our study (7-11%) compared to a US study that reported approximately 58% to 62% of patients with RA (both incident and prevalent cases) using opioids.8 Higher levels of pain3 and coexistence of fibromyalgia3,18 in female patients with IA could explain higher use of these medications. Higher NSAID and opioid use in women in the general population4 could also have been reflected here. Considering the higher risk of women to suffer functional and psychological impairment from opioid use,19 alternative therapy and appropriate rehabilitation services should perhaps be instituted early. Interestingly, oral CS use was higher in male patients with RA than female patients, perhaps due to the higher prevalence of osteoporosis in older female patients.20 Overall sex differences were less prominent in the PsA cohort, possibly due to smaller sample size.
Our study found higher likelihood for DMARD prescriptions with patient-physician sex concordance. Lack of information on patient, physician, and disease characteristics make it difficult to infer the underlying reasons.
Strengths of our study include use of validated case definitions, use of data from a publicly funded healthcare system removing sex biases in drug coverage, and a diverse study population. Limitations of our study include misclassification of patients, residual confounding (eg, disease activity) and lack of information on over-the-counter dispensation of NSAIDs, indications for prescription of pain control medications, and patient access to primary care. Comprehensive data on prescriptions for younger patients is unavailable in Ontario. Our study focused on older patients with incident IA. This represent a subgroup that may be potentially different than the typical patient with newly diagnosed IA. Results should therefore be interpreted cautiously.
In conclusion, our study found higher likelihood of prescriptions for pain control medications in female patients with IA, suggesting higher burden of pain that may be due to suboptimal disease control, comorbidities, or sex dimorphism in pain mechanisms. Further studies could explore sex disparities in prescription patterns in younger patients and compare those with findings in older patients.
ACKNOWLEDGMENT
This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care (MLTC). Parts of this material are based on data and information compiled and provided by the MOH, MLTC, Ontario Health, and the Canadian Institute for Health Information. This document used data adapted from the Statistics Canada Postal CodeOM Conversion File, which is based on data licensed from Canada Post Corporation, and/or data adapted from the Ontario MOH Postal Code Conversion File, which contains data copied under license from Canada Post Corporation and Statistics Canada. We thank IQVIA Solutions Canada Inc. for use of their Drug Information File. We thank the Toronto Community Health Profiles Partnership for providing access to the Ontario Marginalization Index. The analyses, conclusions, opinions, and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources; no endorsement is intended or should be inferred. The abstract of this study was presented as posters at the Canadian Rheumatology Association Annual Scientific Meeting in 2022, 2022 Spondyloarthritis Research and Treatment Network Annual Meeting and Trainee Symposium, European Alliance of Associations for Rheumatology Congress 2022, and American College of Rheumatology Convergence 2022; and as an oral presentation at the Lancet Summit: Sex and Gender in Rheumatology 2022.
Footnotes
ST is supported by an Enid Walker Graduate Student Award for Research in Women’s Health. JW received support from the Arthritis Society Stars Career Development Award (STAR-19-0610). PR holds the RTOERO Chair in Geriatric Medicine at the University of Toronto. LE received support from an Early Researcher Award from the Ontario Ministry of Research, Innovation and Science, and is Canada Research Chair (Tier 2) in Inflammatory Rheumatic Diseases.
LE received educational and research grants and consultation fees from AbbVie, UCB, Eli Lilly, Novartis, Sandoz, Fresenius Kabi, Janssen, BMS, and Pfizer. The remaining authors declare no conflicts of interest relevant to this article.
- Accepted for publication April 11, 2024.
- Copyright © 2024 by the Journal of Rheumatology
REFERENCES
ONLINE SUPPLEMENT
Supplementary material accompanies the online version of this article.
