Frailty & Prefrailty in Patients with RA
TNF-α inhibitors associated with higher infection risk
By Namrata Singh, MD, MSCI, Katherine D. Wysham, MD, James S. Andrews, MD, & Una E. Makris, MD
Why was this study done? Frailty and prefrailty are more common and occur at a younger age in patients with rheumatoid arthritis (RA) than in healthy controls. Biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) are associated with an increased risk of serious infections compared with conventional synthetic DMARDs in patients with RA. To guide shared decision making around biologic and targeted synthetic DMARD use in RA, research is needed to identify traits that determine infection risk. We evaluated the association between frailty and serious infections in a younger population of patients with RA who initiated biologic or targeted synthetic DMARDs.
What were the study methods? Using MarketScan Databases, we identified patients with RA younger than 65 years old who initiated tumor necrosis factor-α (TNF-α) inhibitors, non-TNF inhibitors or targeted synthetic DMARDs, or Janus kinase (JAK) inhibitors between Jan. 1, 2008, and Dec. 31, 2019. The index date was first prescription, and participants contributed data only under one drug class and were censored if they switched drug classes. Participants were categorized as frail or non-frail using a claims-based frailty index. Our primary outcome was time to serious infection requiring hospitalization. We used Cox proportional hazards to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (95% CIs), adjusting for demographics, comorbidity burden and healthcare use.
What were the key findings? A total of 57,980 patients, mean (±SD) age 48.1±10.1 were included; 48,139 (83%) started TNF-α inhibitors, 8,111 (14%) non-TNF inhibitor biologics, and 1,730 (3%) JAK inhibitors. Among these, 3,560 (6%) were categorized as frail. In fully adjusted models, frailty was associated with a significantly higher risk of serious infections (aHR 1.5, 95% CI 1.2–1.9) compared with non-frail RA patients among those who had initiated a TNF-α inhibitor. This was not observed with non-TNF inhibitors (aHR 1.2, 95% CI 0.9–1.7) or among JAK inhibitor users (aHR 3.2, 95% CI 0.9–11.2).
What were the main conclusions? Among individuals with RA who initiated a TNFα inhibitor, those who were frail had a 50% higher risk of serious infections, compared with non-frail patients, even after adjusting for age, comorbidity burden and baseline healthcare use. There was a trend toward a higher risk of infections in other biologic and targeted synthetic DMARD groups, but they did not achieve statistical significance, likely due to lower power.
What are the implications for patients and clinicians? Our findings highlight that frailty status may impact risk of serious infections from biologic and targeted synthetic DMARDs in people with RA. Frailty is an important concept in RA and should be considered to inform holistic, patient-centered treatment plans.
The study: Singh N, Gold LS, Lee J, Wysham KD, et al. Frailty and risk of serious infections in patients with rheumatoid arthritis treated with biologic or targeted-synthetic disease-modifying antirheumatic drugs. Arthritis Care Res (Hoboken). 2023 Dec 20. Online ahead of print.
Premature Mortality Persists in Gout
Analysis of nationwide cohorts in the U.S. & U.K.
By Natalie McCormick, PhD
Why was this study done? Some prior studies showed premature mortality and cardiovascular disease risk among patients with gout compared with people without gout; however, none was adjusted for all of the American College of Cardiology’s atherosclerotic cardiovascular disease (ASCVD) risk factors, nor did they investigate the impact of gout independent of serum urate levels. It is also unknown whether the premature mortality trend has improved with contemporary management approaches, as it has for other rheumatic diseases, including rheumatoid arthritis and lupus.
What were the study methods? We used data from two prospective, nationwide cohorts: U.S. NHANES and U.K. Biobank. In NHANES, we used Cox models to assess the relationship between prevalent gout and mortality risk over 10 years, adjusting for sociodemographics, comorbidities, medication use, alcohol consumption, body mass index, kidney function and all ASCVD risk factors. We then further adjusted for serum urate levels. Temporal trends were assessed by comparing premature mortality in the early cohort (1988–1994) and late cohort (1997–2016). We replicated the analysis among individuals with incident gout in the U.K.
What were the key findings? We documented premature all-cause and cardiovascular mortality among patients with gout in both the U.S. and the U.K., even after adjusting for serum urate levels and all other risk factors. Premature mortality has not improved over time among U.S. patients with gout, despite improvements in survival in the general population. In both cohorts, the risk for premature mortality was greater among women than men and more prominent among patients who were Black.
What were the main conclusions? These data suggest premature mortality is potentially driven by gout-specific disease mechanisms beyond serum urate pathways and conventional ASCVD risk factors, such as gouty inflammation and flares. Our findings also suggest overall shortcomings in care, particularly among women and, possibly, among patients who are Black.
What are the implications for patients and clinicians? Although a need to enhance implementation of guideline-recommended gout care likely exists, particularly among underserved groups, long-term, targeted, anti-inflammatory agents, such as low-dose daily colchicine (recently approved by the U.S. Food & Drug Administration [FDA] for prevention of cardiovascular disease at large), may also have a role, in addition to standard gout and cardiovascular prevention and care.
The study: McCormick N, Lin K, Yokose C, et al. Unclosing premature mortality gap among patients with gout in the US general population, independent of serum urate and atherosclerotic cardiovascular risk factors. Arthritis Care Res (Hoboken). 2024 Jan 8.
Rheumatologist Recruitment & Multidisciplinary Care Incentives Improve Patient Access
Evidence from British Columbia
By Norma K. Biln (PhD candidate), Daphne Guh, MSc, Nick Bansback, PhD, Kam Shojania, MD, & Mark Harrison, PhD
Why was this study done? In 2010, the province of British Columbia (B.C.), Canada, was facing a crisis in the provision of rheumatology services; there were insufficient rheumatologists, and half planned to retire within a decade. In response, B.C. expanded recruitment of rheumatologists and added new billing codes—multidisciplinary care assessments—that facilitated rheumatologists’ employing nurses to provide team/multidisciplinary care. We sought to understand how these changes were associated with access to rheumatology services in B.C.
What were the study methods? We used linked, de-identified, individual-level data on healthcare utilization by residents of B.C. between 2010 and 2020 to identify people seeing a rheumatologist for the first time. We calculated the time between referral to a rheumatologist by a general practitioner and the rheumatologist visit, and for people with RA, from referral to their first disease-modifying anti-rheumatic drug (DMARD). We described changes in these times over the study period and explored associations between these times and patient characteristics and system factors.
What were the key findings? The number of patients having a first visit to a rheumatologist increased by 31% between 2010 and 2020. The proportion of first visits represented by people with inflammatory arthritis increased from 28% to 51%. The median time from referral to first visit decreased by 22 days (35%), and for people with RA, time to first DMARD decreased by four days (6%). Shorter times from referral to first DMARD were associated with being male, living in metropolitan areas and being under the care of a rheumatologist who employed a nurse.
What were the main conclusions? Increasing rheumatologist supply and introducing incentives for multidisciplinary care in B.C. was associated with improved patient access to rheumatology care and referral patterns (based on the percentage of patients with inflammatory arthritis) over time. Still, the time to DMARD start from referral for people with RA remains longer than is recommended. Concerningly, women and those living outside metropolitan areas do not see the same improvements.
What are the implications for patients and clinicians? These findings may be useful for other publicly funded healthcare jurisdictions seeking to expand patient access to rheumatology care and present an opportunity for innovative clinical service redesign. However, improvement is still needed to meet treatment targets and tackle inequalities in access to care.
The study: Biln NK, Guh D, Bansback N, et al. The association of rheumatologist supply and multidisciplinary care with timely patient access to rheumatologists: Evidence from British Columbia, Canada. Arthritis Care Res (Hoboken). 2024 Apr;76(4):444–453.
