076 Assessment of pain improvement in rheumatoid arthritis patients treated with baricitinib, who were inadequate responders to methotrexate and tumor necrosis factor inhibitors
Bibliographic record
Abstract
Background: During the development programme, baricitinib (BARI) demonstrated greater and faster pain relief relative to placebo (PBO) and active comparator in different RA populations. Here, we summarise the findings from two recent post hoc analyses focused on the effect of BARI on pain in two clinically relevant patient populations: methotrexate-inadequate responders (MTX-IR; RA-BEAM) and tumor necrosis factor inhibitor-inadequate responders (TNFi-IR; RA-BEACON). Methods: In both clinical trials (RA-BEAM and RA-BEACON), pain was assessed with a visual analog scale (VAS, 0-100 mm) at each study visit. In RA-BEAM, 1,305 patients on stable background MTX were randomized 3:3:2 to PBO, BARI 4-mg, or adalimumab (ADA) 40-mg. The likelihood of achieving ⩾30%, ⩾50%, and ⩾70% pain VAS improvement through Week 24 and the median time when 50% of patients achieved these pain improvement thresholds was assessed with Cox proportional hazard models and the cumulative incidence estimate. Analyses were not adjusted for multiplicity. In RA-BEACON, 527 patients were randomised to placebo (n = 176), BARI 2-mg (n = 174), or 4-mg (n = 177) once daily for 24 weeks. Approximately 40% of patients had received >1 TNF inhibitor and a quarter of patients had received ⩾3 bDMARDs, representing patients with highly refractory disease. The proportion of patients achieving ⩾30%, ⩾50%, and ⩾70% pain relief at Week-12 was compared between BARI 2-mg or 4-mg and PBO using logistic models. Missing pain values were imputed using modified last observation-carried-forward. Results: In the MTX-IR population, BARI-treated patients were more likely to achieve at least 30%, 50%, and 70% pain improvement than PBO and ADA with HR of 1.7, 1.9 and 2.5, respectively (p < 0.001) compared to PBO, and 1.1 (p = 0.145), 1.2 (p = 0.032) and 1.3 (p = 0.003) compared to ADA. The median time for 50% of patients to achieve at least 30%, 50%, and 70% pain improvement, respectively, was 1.9, 4.0 and 12.4 weeks for BARI, 2.0, 7.9 and 20.0 weeks for ADA, and 4.6, 14.0 and >24 weeks for PBO. In the TNFi-IR population, at Week-12, significantly more patients achieved ⩾30%, ⩾50%, and ⩾70% pain relief with BARI 2-mg or 4-mg vs PBO (p < 0.05, for all comparisons). Consistent improvements were observed regardless of baseline pain. Regardless of treatment history, patients receiving BARI 2-mg or 4-mg were more likely to reach all pain relief thresholds than placebo. Conclusion: In both MTX-IR and TNFi-IR populations, BARI demonstrated greater pain improvement than comparators at Weeks 24 and 12, respectively. Disclosures: P.C. Taylor: Grants/research support; Celgene, Eli lilly and company, Galapagos, UBC. Consultant for: AbbVie, Eli Lilly and Company, Galapagos, GlaxoSmithKline, Pfizer, UCB, Biogen, Sandoz, Novartis, Gilead and Janssen. R. Fleischmann: Consultancies; AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Celltrion, GSK, Janssen, Eli Lilly and company, Novartis, Pfizer, Samsung, Sanofi-Aventis, tahio. Grants/research support; AbbVie, Amgen, AstraZeneca, Bristol-Myers squibb, Celgene, Centrexion, Genetech, GlaxosmithKline, Janssen, Eli Lilly and company, Merck, Pfizer, Regeneron, Roche, Sanofi, Aventis, UCB. T. Takeuchi: Grants/research support; AbbVie, Asahi Kasei Medical, Astellas Pharma, AstraZeneca, BMS, Chugai Pharma, Daiichi Sankyo, Eisai, Lilly, Janssen, Mitsubishi Tanabe Pharma, Nipponkayaku, Novartis, Pfizer Japan, Takeda, Taiho, Tai. J. Pope: Consultancies; AbbVie, Amgen, Bayer, BMS, Celtrion, Lilly, Merck, Novartis, Pfizer, Roche, UCB. Grants/research support; Amgen, Bayer, BMS, GSK, Merck, Novartis, Pfizer, Roche, UCB, M.C. Genovese: Grants/research support; Eli Lilly and Company, Abbvie. B. Zhu: Other; Employee of Eli Lilly and Company. C. Gaich: Shareholder/stock ownership; Eli Lilly and Company. Other; Employee of Eli Lilly and Company. X. Zhang: Other; Employee of Eli Lilly and Company. C. Dickson: Other; Employee at Eli Lilly and Company. A. Quebe: Shareholder/stock ownership; Eli Lilly and Company. Other; Employee of Eli Lilly and Company. F. De Leonardis: Shareholder/stock ownership; Eli Lilly and Company. Other; Employee of Eli Lilly and Company. A. Cardoso: Shareholder/stock ownership; Eli Lilly and Company. Other; Employee of Eli Lilly and Company. I. Kouris: Other; Employee of Eli Lilly and Company. P. Durez: Consultancies; Lilly, BMS, Merck, Pfizer, Sanofi, Janssen. Honoraria; Lilly, BMS, Merck, Pfizer, Sanofi, Janssen.
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 | 0.003 | 0.003 |
| 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".