106. Long-Term Safety of Rituximab: Pooled Analysis of the Rheumatoid Arthritis Global Clinical Trial Programme Over 11 Years
Bibliographic record
Abstract
Background: This analysis evaluated the long-term safety of rituximab (RTX) in RA patients in a global clinical trial programme. Methods: Pooled observed case analysis of safety data from patients with moderate to severe active RA treated with RTX + MTX. Patients were re-treated based on physician’s determination of clinical need and evidence of active disease (defined as either SJC and TJC ≥ 8 or DAS28 ≥ 2.6). Subgroup analysis of patients with follow-up >5 years was undertaken. Pooled data from patients who received placebo during placebo-controlled study periods were also analysed. Results: As of Sep 2012, 3595 patients (All-Exposure population) had received up to 20 courses of RTX over the 11-year observation period (14 816 pt-yrs). Of these patients, 1246 had >5 years follow-up. The placebo population comprised 818 patients (1107 pt-yrs) with a mean follow-up of 1–1.5 years. In the All-Exposure population, infusion-related reaction (IRR) was the most frequent adverse event (AE); most were grade 1 or 2, were rarely serious (0.5%), and primarily occurred following the 1st infusion of the 1st course (799/3595 patients; 22%). Rates per 100 pt-yrs for AEs, serious AEs (SAEs), and infections were not increased when compared with placebo. The overall serious infection rate in RTX-treated patients was 3.76 events/100 pt-yrs (2.71 events/100 pt-yrs in patients treated for > 5 yrs) and was comparable to that observed in the placebo population (3.79 events/100 pt-yrs). Pneumonia was the most frequently reported serious infection (2% of RTX patients). There were no cases of hepatitis B reactivation. Serious opportunistic infections were rare (0.05/100 pt-yrs in RTX patients vs 0.09/100 pt-yrs in placebo). One confirmed case of PML in the RA clinical trial programme has been reported, as previously described in 2009. Following RTX treatment, low immunoglobulin (Ig) concentrations (particularly IgM, less often IgG) were observed. For both Ig classes, serious infection rates were similar before and during/after development of low Ig. No increased risk of malignancy over time or course was evident, and MI rates (0.39/100 pt-yrs) were consistent with rates in the general RA population (0.48–0.59/100 pt-yrs).
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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 | 0.018 | 0.047 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.013 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| 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".