A Shift in Prescribing Patterns
Safety issues prompt discontinuation of tofacitinib
By Stephanie Song, MD, & Joshua F. Baker, MD, MSCE
Why was this study done? The ORAL Surveillance study highlighted risks of cardiac events, thromboembolism (VTE) and malignancy associated with use of Janus kinase inhibitors (JAKi). We sought to determine the impact of safety data on prescribing patterns by describing the characteristics of patients initiating and discontinuing advanced therapies for rheumatoid arthritis (RA) before and after the trial results were released in January 2021.
What were the study methods? This was a national retrospective study of U.S. Veterans with RA receiving advanced therapies including tofacitinib, tumor necrosis factor inhibitors (TNFi’s), and non-TNFi agents from April 2019 through September 2022. Patient characteristics were defined for each therapy initiation. We tested for interactions to determine whether changes observed in characteristics over time for tofacitinib users were different from changes observed for the other therapies. Time to discontinuation for active users at the time of the press release was determined, censoring for death and end of follow-up. We used Cox models adjusted for age, sex and duration of therapy and evaluated associations between patient characteristics and therapy discontinuation, testing for interaction across the therapy types.
What were the key findings? Characteristics of patients initiating tofacitinib after the release of safety data in January 2021 included lower mean age, lower proportion of men, less comorbidity and fewer cardiovascular comorbidities. Similar changes were not seen in patients initiating TNFi’s or non-TNFi’s. The likelihood of discontinuation was higher for tofacitinib than for TNFi’s, and the higher rate of tofacitinib discontinuation was more pronounced in the presence of cardiovascular comorbidities.
What were the main conclusions? Significant changes in age, gender and cardiovascular comorbidity burden were seen in patients initiating tofacitinib following the release of safety data. Patients using tofacitinib were more likely than those using TNFi’s to discontinue therapy, and this finding was pronounced in the setting of cardiovascular comorbidities.
What are the implications for patients and clinicians? This study saw a marked change in characteristics of patients initiating and discontinuing tofacitinib after the release of safety data compared with other advanced therapies. It emphasizes the importance of safety studies and their impact on prescribing practices.
The study: Song S, England BR, Sauer B, et al. Changes in characteristics of patients initiating and discontinuing advanced therapies for rheumatoid arthritis following the release of safety data. Arthritis Care Res (Hoboken). 2023 Nov 1. doi: 10.1002/acr.25268. Epub ahead of print.
PMR & Glucocorticoids
Analysis from the ACR RISE registry
By Sebastian E. Sattui, MD, MS
Why was this study done? Polymyalgia rheumatica (PMR) is one of the most common rheumatic diseases. However, critical knowledge gaps regarding the use of both glucocorticoid and glucocorticoid-sparing treatments in PMR exist. The goal of this study was to describe current treatment practices, including the use of glucocorticoids and glucocorticoid-sparing agents, in a national cohort of individuals with PMR under rheumatology care.
What were the study methods? Patients with PMR were identified in the ACR Rheumatology Informatics System for Effectiveness (RISE) registry from 2016–22. Use of glucocorticoids and immunomodulatory antirheumatic medications used as glucocorticoid-sparing agents were examined during a 24-month follow-up. The main analysis focused on a subgroup of patients new to rheumatology practices, the majority with presumed new-onset PMR. Multivariate logistic regressions were performed to identify factors associated with persistent glucocorticoid and glucocorticoid-sparing agent use at 12–24 months.
What were the key findings? In the main analysis, 16,703 patients with PMR were included. At 12–24-month follow-up, 63.8% of patients remained on glucocorticoids, while only 39% of patients were receiving a glucocorticoid-sparing agent. Methotrexate (19.5%) was the most frequent choice of glucocorticoid-sparing agent. Female sex, higher comorbidity count and use of glucocorticoid-sparing agent at 24 months were associated with persistent glucocorticoid use; higher comorbidity count and obesity (BMI ≥35 kg/m2) were associated with use of glucocorticoid-sparing agents at 12–24 months.
What were the main conclusions? Despite the need for prolonged glucocorticcoid use, a minority of patients with PMR under rheumatology care received a glucocorticoid-sparing agent at 12–24 months. Further information with regard to value, timing and balancing the risks and benefits is needed.
What are the implications for patients? Prolonged glucocorticoid use is frequent in patients with PMR. Specific characteristics were associated with prolonged use of glucocorticoids and could identify patients for whom glucocorticoid-sparing therapies should be considered.
What are the implications for clinicians? Our study is timely given increased data on the use of biologic drugs for the treatment of PMR, including the recent U.S. Food & Drug Administration approval of sarilumab for treatment of refractory/relapsing PMR. Use of glucocorticoid-sparing agents should be considered in patients with persistent disease and glucocorticoid requirement.
The study: Sattui SE, Xie F, Clinton C, et al. Treatment of polymyalgia rheumatica by rheumatology providers: Analysis from the ACR Rheumatology RISE registry. Arthritis Care Res (Hoboken). 2023 Aug 10. doi:10.1002/acr.25.216. Online ahead of print.
Best Practices for Infection Screening
Reducing risks for patients with autoimmune rheumatic disease prior to starting new DMARD prescriptions
By Hailey Baker, MD, MS, & Abhijeet Danve, MBBS, MD, MHS
Why was this study done? Starting biologic and small molecule disease-modifying anti-rheumatic drugs (DMARDs) in patients with undiagnosed hepatitis or tuberculosis (TB) carries an increased risk of morbidity and mortality. Guidelines recommend screening for hepatitis B virus (HBV), hepatitis C virus (HCV) and TB prior to initiation of DMARDs; however, adherence to these guidelines varies widely. Best practice advisories (BPAs) are built into the electronic medical record (EMR) and can be used to notify clinicians when a patient does not have recent infectious screening tests. We implemented a BPA to alert providers of potential gaps in screening and assess the impact of the BPA on screening proportions for TB, HBV and HCV.
What were the study methods? We included patients 18 years or older with an autoimmune rheumatic disease (ARD) and at least one visit to our rheumatology practice between Oct. 1, 2017, and March 3, 2022. We assessed screening practices with new DMARD prescriptions for HBV, HCV and TB before and after implementation of the BPA on Dec. 1, 2020. We performed multivariable logistic analyses including patient characteristics (age, sex, and race and ethnicity) and clinician training level (i.e., attending, fellow or advanced practice registered nurse [APRN]).
What were the key findings? We observed an approximate 20% increase in screening proportions for TB, HCV, HBcAb and HBsAg after implementation of the BPA. Multivariable logistic analysis showed that training level, patient age and patient sex all influenced screening proportions prior to the BPA, but there was no statistically significant influence of any variable after implementation of the BPA. Implementation of the BPA increased the adjusted odds of screening by 2.2 to 2.5 times when adjusted for age, sex and clinician training level.
What were the main conclusions? Our pre-BPA screening proportions were low (ranging from 32% for HBcAb to 66% for TB), similar to other studies. A BPA has the ability to improve patient safety, enhance clinician efficiency and eliminate biases in screening.
What are the implications for patients and clinicians? Screening for HBV, HCV and TB prior to DMARD initiation allows patients to have their potentially undiagnosed infections treated to reduce risk of infectious complications with immunosuppression. A BPA uses technology built into the EMR to reduce the burden on clinicians during busy clinics. Alerts like the BPA may contribute to clinician pop-up fatigue, but a post-BPA survey showed that respondents felt it helped them manage their patients more efficiently (5 of 9 responders).
The study: Baker H, Fine R, Suter F, et al. Implementation of a best practice advisory to improve infection screening prior to new prescriptions of biologics and targeted synthetic drugs. Arthritis Care Res (Hoboken). 2023 Jun 29. doi: 10.1002/acr.25181. Online ahead of print.