Comparative effectiveness and safety of five Janus kinase inhibitors in real-world clinical practice: the multicentre ANSWER cohort
Rheumatology · 27 Oct 2026
† Impact is the editorial-priority score. All scores are out of 100. Clinical is a stored clinical-importance score from the earlier method; it has not been recalculated.
Why it matters
JAK inhibitors are a common next step in refractory RA, and real-world persistence data help clinicians choose among agents, especially after prior IL-6 or JAK inhibitor failure.
The evidence
This Japanese multicentre registry study compared five oral Janus kinase (JAK) inhibitors for rheumatoid arthritis across 1,798 treatment courses in 1,240 patients, looking at how long patients stayed on each drug before stopping for lack of effect or side effects. After adjustment, upadacitinib (HR 0.33, 95% CI 0.24 to 0.47) and filgotinib (HR 0.59, 95% CI 0.42 to 0.85) were less often stopped for ineffectiveness than tofacitinib. For side effects, the only significant difference was upadacitinib versus peficitinib (HR 0.57). Improvement in disease activity scores was broadly similar across drugs.
Treatment discontinuation due to ineffectiveness: Hazard ratio 0.33 (95% CI 0.24 to 0.47; ratio). Interpret in the study's stated comparison; this alone does not establish a treatment's causal effect.
Why this rigour score?
Retrospective cohortDesign starting point: 29.6
Raised the score
- Competing risks handled+4.3
Lowered the score
No negative adjustments recorded.
Methods at a glance
Recorded assessment- Confounding adjustmentNot applicable
- Covariate balance confirmedNot applicable
- Outcome assessors blindedNot reported
- Comparable start of follow-upMet
- Adequate statistical powerNot reported
- Prospective registrationNot met
Not reported does not mean not done. Checks have different weights; this is not a count of boxes ticked.
See the full score breakdown
- Study design starting point
- 29.6
- Competing risks handled
- +4.3
- Journal prior (not an observed method)
- +0.8
- Final rigour score rounded
- 35 / 100
Study design sets the starting point and a ceiling of 72. Recorded methods then adjust the score. Points are shown to one decimal place; the final score uses unrounded values.
Checklist from the stored appraisal. “Not met” describes the recorded criterion; it does not always produce a deduction. This overview supports reading the full study.
For journal club
1.For an RA patient who has already failed an IL-6 inhibitor or another JAK inhibitor, how should these persistence data influence which JAK inhibitor is chosen next?
2.How should older RA patients be counselled about the risk of stopping a JAK inhibitor because of infections or herpes zoster, and what monitoring or vaccination steps follow from that?
Original publication title
Comparative effectiveness and safety of five Janus kinase inhibitors in real-world clinical practice: the multicentre ANSWER cohort