Age-based (<65 vs ≥65 years) incidence of infections and serious infections with tofacitinib versus biological DMARDs in rheumatoid arthritis clinical trials and the US Corrona RA registry
Bibliographic record
Abstract
A randomised, open-label, blinded endpoint post-authorisation safety study (Study A3921133; NCT02092467; database not locked and subject to change) evaluated the safety of tofacitinib 5 mg and 10 mg twice daily (BID) versus tumour necrosis factor inhibitors (TNFi) (adalimumab/etanercept) in rheumatoid arthritis (RA) patients aged ≥50 years with ≥1 cardiovascular risk factor. An ad hoc interim safety analysis of Study A3921133 reported incidence rates (IRs) per 100 patient-years (95% CIs) for fatal infections (within 28 days of treatment) and non-fatal serious infection events (SIEs), respectively: tofacitinib 5 mg BID, 0.18 (0.07 to 0.39) and 3.35 (2.78 to 4.01); tofacitinib 10 mg BID, 0.22 (0.09 to 0.46) and 3.51 (2.93 to 4.16); TNFi, 0.06 (0.01 to 0.22) and 2.79 (2.28 to 3.39).1 SIEs risk (fatal/non-fatal) was further increased with tofacitinib in patients aged >65 years versus younger patients; therefore, the European Medicines Agency recommended that older patients should receive tofacitinib when there is no suitable alternative treatment.2 Further to these recommendations, we sought to assess age-based (<65 vs ≥65 years) SIE risk in RA patients receiving tofacitinib in Phase 2, 3 and 3b/4 tofacitinib studies with a TNFi control/comparator arm,3–5 and in the US Corrona RA registry. The clinical data set included 2180 patients (tofacitinib 5 mg BID, n=1064 (943.4 patient-years); tofacitinib 10 mg BID, n=306 (236.6 patient-years); adalimumab, n=643 (554.3 patient-years); placebo, n=167 (108.1 patient-years)). Overall, 1841 (84.4%) patients were aged <65 years and 339 (15.6%) ≥65 years. Crude IRs (patients with events/100 patient-years) and HRs were calculated for all first infections and first SIEs, overall and by age. For all infections (online supplemental figure S1), IRs and infection risk (by HRs) were higher with active treatments versus placebo, and similar across active treatments and age groups. For SIEs (figure 1), IRs were higher in older versus younger patients for active treatments, …
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.016 | 0.018 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.004 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".