Interruptions of biological and targeted synthetic disease-modifying antirheumatic drugs in rheumatoid arthritis: a descriptive cohort study assessing trends in patient characteristics in Switzerland

BMJ Open. 2022 Mar 15;12(3):e056352. doi: 10.1136/bmjopen-2021-056352.

Abstract

Objectives: To identify differing patient characteristics at the time of stop and restart of biological or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in rheumatoid arthritis (RA), stratified by stop reason.

Design: Explorative descriptive cohort study.

Setting: Swiss Clinical Quality Management in Rheumatic Diseases (1999-2018).

Participants: Patients with RA who stopped their first b/tsDMARD.

Outcome measures: We assessed patient characteristics at b/tsDMARD stop and restart, stratified by stop reason (non-response, adverse event, remission, other).

Results: Among 2526 eligible patients, most patients (38%) stopped their b/tsDMARD due to non-response. At treatment stop, most characteristics did not differ by stop reason, yet some differed significantly (p<0.0001, those stopping due to remission had lowest median Health Assessment Questionnaire measurements (0.1) and were least likely to use leflunomide combination therapy (3.9%) and to have fibromyalgia (6.7%)). The majority of patients restarted b/tsDMARDs without changes in patient characteristics at restart. However, among the 48% of patients who restarted a b/tsDMARD after having previously stopped due to remission or other reasons, disease activity measurements were significantly worse compared with treatment stop date (mean disease activity score-erythrocyte sedimentation rate score of 2.0 at b/tsDMARD restart vs 3.5 at treatment stop (p<0.0001)). Furthermore, we observed non-significant trends in several patient characteristics (eg, higher proportion of women (75% at b/tsDMARD restart vs 70% at treatment stop, p=0.38), patients with seropositivity (anti-citrullinated protein antibody positive 67% vs 58%, p=0.25), with family history of rheumatic diseases (24% vs 20%, p=0.15), osteoarthritis/arthroplasty (25% vs 20%, p=0.34) and the metabolic syndrome (11% vs 6%, p=0.15).

Conclusion: Differences among patient characteristics across b/tsDMARD cessation strata were few. However, differences between stop and restart may have identified an RA phenotype that is challenging to treat. Further research on identifying the patient characteristics predictive of successful drug holidays and the optimal time to initiate and stop a drug holiday is warranted.

Keywords: epidemiology; public health; rheumatology.

MeSH terms

  • Antirheumatic Agents* / therapeutic use
  • Arthritis, Rheumatoid* / chemically induced
  • Arthritis, Rheumatoid* / drug therapy
  • Biological Products* / therapeutic use
  • Cohort Studies
  • Female
  • Humans
  • Switzerland / epidemiology
  • Treatment Outcome

Substances

  • Antirheumatic Agents
  • Biological Products