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Why most (but perhaps not all) DMARDs work equally well.

Robert B M Landewé1, Alexandre Sepriano2, Sytske Anne Bergstra3

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Summary

Responses to biologic or targeted-synthetic DMARDs in rheumatic diseases are similar, except for Janus-kinase inhibitors (JAK inhibitors). JAK inhibitors show a "JAK-bonus," potentially due to inflammation-independent effects on pain and fatigue.

Keywords:
Rheumatoid arthritis DMARDs JAK-inhibitors Randomized clinical trials Non-specific treatment effects

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Area of Science:

  • Rheumatology
  • Pharmacology
  • Clinical Trials

Background:

  • Randomized clinical trials (RCTs) in rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis show similar responses to biologic and targeted-synthetic DMARDs.
  • A notable exception is Janus-kinase inhibitors (JAK inhibitors), which consistently demonstrate a higher response rate across trials, termed the "JAK-bonus."

Purpose of the Study:

  • To investigate the reasons behind the similar efficacy of DMARDs in rheumatic diseases.
  • To provide a potential explanation for the observed "JAK-bonus" associated with JAK inhibitors.

Main Methods:

  • Comparative analysis of efficacy data from placebo-controlled and head-to-head randomized clinical trials.
  • Examination of primary outcome measures across different DMARD classes in specific rheumatic diseases.

Main Results:

  • Efficacy of biological and targeted-synthetic DMARDs is remarkably consistent within the same disease and outcome measures.
  • JAK inhibitors exhibit an approximate 10% higher response rate compared to other DMARDs across multiple trials.
  • This "JAK-bonus" suggests potential inflammation-independent effects of JAK inhibitors.

Conclusions:

  • Drug treatment for rheumatic diseases may involve more than just inhibiting inflammation.
  • JAK inhibitors might exert beneficial effects on pain, fatigue, and well-being independent of their anti-inflammatory action.
  • The findings highlight a nuanced understanding of DMARD efficacy beyond inflammation suppression.