Safety of T-cell co-stimulation modulation with abatacept in patients with rheumatoid arthritis.
Bibliographic record
Abstract
Abatacept selectively modulates the CD80/CD86:CD28 co-stimulatory signal required for full T-cell activation, and has been approved for the treatment of rheumatoid arthritis (RA) in combination with methotrexate in a number of countries, including the United States, Canada, and the European Union. As with any new agent, it is important to assess the safety and tolerability of abatacept, and hence an integrated safety analysis of five randomized, placebo-controlled, double-blind core abatacept clinical trials was performed. The 2,944 patients enrolled had active RA and were receiving a variety of biologic and non-biologic background disease-modifying antirheumatic drugs. Overall, 1,955 patients were treated with abatacept during the double-blind periods, and 2,688 during the cumulative double-blind and open-label periods (yielding 4764 patient-years of exposure in total). Overall frequencies of adverse events (AEs; 88.8% vs. 85.1%), serious AEs (SAEs14.0% vs. 12.5%) and malignancies (1.4% vs. 1.1%) were similar in abatacept- versus placebo-treated patients, respectively (regardless of the potential relationship to the study therapy). Discontinuations due to SAEs were 2.8% in the abatacept group vs. 1.6% in the placebo group. The frequency of serious infections was low overall (3.0% vs. 1.9% in abatacept- versus placebo-treated patients, respectively). Acute infusional AEs (9.8% vs. 6.7% in the abatacept versus placebo groups, respectively) were mostly mild-to-moderate in intensity. Safety data through cumulative exposure were consistent with those from the double-blind periods; there was no evidence of an increase in the incidence of serious infections or malignancies with increasing exposure to abatacept. Abatacept was associated with low levels of immunogenicity, with no detectable association between immunogenicity and safety or efficacy. Abatacept treatment did not result in a higher rate of seroconversion for anti-nuclear or anti-dsDNA antibodies versus placebo, and was associated with a similar frequency of autoimmune events versus placebo (1.4% vs. 1.8%, respectively). Moreover, treatment with abatacept may not markedly impair the response to vaccination in healthy volunteers or RA patients. Overall, these findings suggest that abatacept has acceptable safety and tolerability in patients with RA. Ongoing follow-up will monitor whether these features are maintained over long-term abatacept use.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.005 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".