Effectiveness of TNF- inhibitors, abatacept, IL6- inhibitors, and JAK- inhibitors in 31 846 patients with rheumatoid arthritis in 19 registers from the ‘JAK- pot’ collaboration
Summary
JAK- inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. The authors of this article, led by GCIR member Prof. Axel Finckh, aimed to compare the effectiveness of four current second-line therapies of RA with different modes of action in an international study of 31 846 patients.
In this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin- 6 inhibitors (IL- 6i), abatacept (ABA) or JAKi were included. The authors compared the effectiveness of these treatments in terms of drug discontinuation and Clinical Disease Activity Index (CDAI)* response rates at 1 year. Analyses were adjusted for patient, disease and treatment characteristics, including lines of therapy and accounted for competing risk.
Discontinuation issues were similar across all treatments. The main single reason for stopping treatment was ineffectiveness. Compared with TNFi, JAKi were less often discontinued for ineffectiveness, as was IL- 6i, and more often for adverse events. Adjusted CDAI response rates at 1 year were similar between TNFi, JAKi, and IL- 6i and slightly lower for ABA.
The adjusted overall drug discontinuation and 1-year response rates of JAKi and IL- 6i were similar to those observed with TNFi. Compared with TNFi, JAKi were more often discontinued for adverse events and less for ineffectiveness, as were IL- 6i.
Read full article: doi:10.1136/ annrheumdis-2022-222586
Why is this study important?
For patients with rheumatoid arthritis with an inadequate response or contraindications for conventional treatment, several second-line therapy options exist from which rheumatologists and patients can choose. Only a limited number of small studies have evaluated the effectiveness of these treatments.
This large comparative effectiveness analysis, involving over 30 000 treatment courses, is the first to evaluate real-life effectiveness and safety outcomes among four common available treatment alternatives and found similar discontinuation rates and Clinical Disease Activity Index response*, although discontinuation reasons tended to differ between treatments, with more discontinuation for safety with JAK- inhibitors, but less for effectiveness.
Considering similar effectiveness among these treatments, this study calls for the evaluation of other outcomes that could influence treatment choices, such as patient-reported outcomes, comorbidities, tolerability, safety, or cost-effectiveness.
(*) The CDAI is a useful clinical composite score for following patients with rheumatoid arthritis. The CDAI is the sum of 4 outcome parameters: tender and swollen joint counts (28 joints assessed) and patient’s and physician’s global assessments of disease activity (on a 0–10-cm visual analog scale). The range of possible scores is 0–17.