Reasons for Multiple Biologic and Targeted Synthetic Dmard Switching and Characteristics of Treatment Refractory Rheumatoid Arthritis

Abstract

Objective: Switching biologic and targeted synthetic DMARD (b/tsDMARD) medications occurs commonly in RA patients. We categorized reasons for b/tsDMARD switching and investigated characteristics associated with treatment refractory RA.

Methods: Within the Mass General Brigham RA electronic health record (EHR) cohort, we identified RA patients prescribed ≥1 TNF-α inhibitor (TNFi) between 2001-2017. From the subset prescribed ≥2 additional b/tsDMARDs, we randomly selected 400 patients for manual chart review to determine reasons for medication switching. We defined treatment refractory RA as not achieving low disease activity (<3 tender or swollen joints on <10mg of daily prednisone equivalent) on the first two b/tsDMARDs. We compared demographic, lifestyle, and clinical factors between treatment refractory RA and patients who initiated TNFi but were not treated with multiple b/tsDMARDs.

Results: We identified 5297 RA patients prescribed TNFi and 929 (33%) who were prescribed ≥2 additional b/tsDMARDs. The most common reasons for medication switching were loss of efficacy (39.2% of switches), primary inefficacy (32.0%), and non-allergic adverse events (10.5%). Of patients prescribed ≥3 b/tsDMARDs, 14% had treatment refractory RA. A higher proportion of treatment refractory RA patients were female (89.4% vs. 75.8%, p=0.047), but no other demographic, lifestyle, or RA clinical factors differentiated treatment refractory RA from TNFi initiators who did not require multiple b/tsDMARDs.

Conclusions: In a large EHR-based RA cohort, the most common reasons for b/tsDMARD switching were loss of efficacy, primary inefficacy, and nonallergic adverse events (e.g. infections, leukopenia, psoriasis). Clinical, demographic, and lifestyle factors were insufficient for differentiating b/tsDMARD responders from nonresponders.

Note:
Funding Declaration: GCM is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers T32 AR007530 and T32 AR055885) and the VERITY Pilot & Feasibility Award. KPL is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant number R21 AR078839), the Harold and DuVal Bowen Fund, and the Bechara Foundation.

Conflicts of Interest: MEW reports research support from Bristol Myers Squibb, Aqtual, Abbvie, and Janssen; consultancy for Abbvie, Aclaris, Amgen, Aqtual, Bristol Myers Squibb, CorEvitas, Glaxo Smith Kline, Gilead, Horizon, Johnson & Johnson, Lilly, Pfizer, Rani, Revolo, Saniofi, Scipher, Sci Rhom, Set Point, and Tremeau; and stock or stock options from Canfite, Inmedix, Scipher. Other authors report no competing interests.

Ethical Approval: This study was approved by the Mass General Brigham IRB, protocol number 2020P002577. Due to retrospective nature of the research, written informed consent was waived.