Effects of nintedanib in patients with progressive fibrosing interstitial lung disease associated with rheumatoid arthritis (RA-ILD) in the INBUILD trial*
Bibliographic record
Abstract
Background In the INBUILD trial with progressive fibrosing ILDs other than idiopathic pulmonary fibrosis (IPF), nintedanib reduced the FVC decline (mL/year) over 52 weeks by 57% versus placebo. Objectives To assess the rate of decline in FVC in subjects with RA-ILD in INBUILD. Methods Subjects had a chronic fibrosing ILD other than IPF, reticular abnormality with traction bronchiectasis (with or without honeycombing) of >10% on HRCT, FVC ≥45% predicted, DL CO ≥30%–<80% predicted, and met criteria for progression of ILD within the 24 months before screening, despite appropriate management in clinical practice. Patients taking stable doses of approved medications to treat RA or connective tissue disease could participate, except those taking azathioprine, cyclosporine, mycophenolate mofetil, tacrolimus, rituximab, cyclophosphamide, or oral glucocorticoids >20 mg/day. We analysed the FVC decline (mL/year) over 52 weeks and adverse events (AEs) in RA-ILD. Results 663 subjects received trial medication, 89 had RA-ILD (42 nintedanib, 47 placebo), 60.7% were male, 64.0% were current or former smokers, 86.5% had a usual interstitial pneumonia (UIP)-like pattern on HRCT; 93.3% had rheumatologist confirmed RA diagnosis. At baseline, 21.3% were taking biologic disease-modifying anti-rheumatic drugs (DMARDs), 53.9% non-biologic DMARDs and 73.0% glucocorticoids (≤20 mg/day prednisone or equivalent). Mean (SD) age was 66.9 (9.6) years, time since RA-/ILD diagnosis was 9.9 (9.4)/ 3.6 (3.2) years, FVC 71.5 (16.2) % predicted and C-reactive protein 13.7 (22.5) mg/L. Consistent with the overall trial population the adjusted mean (SE) FVC decline over 52 weeks was -82.6 (41.3) mL/year with nintedanib vs. -199.3 (36.2) mL/year with placebo (difference 116.7 mL/year [95% CI 7.4, 226.1]; p=0.037) (Figure) and the most common AE in RA-ILD was diarrhoea (reported in 54.8% of the nintedanib and 25.5% of the placebo group). AEs led to permanent discontinuation of trial drug in 19.0% of subjects in nintedanib and 12.8% in placebo group. Conclusions In INBUILD, nintedanib slowed the FVC decline in patients with progressive fibrosing RA-ILD, with AEs that were manageable for most patients. The efficacy and safety of nintedanib in subjects with RA-ILD were consistent with those observed in the overall trial population. Presented at EULAR 2021 Abb. 1 presented at EULAR 2021, presenting on behalf of the authors. Publication History Article published online: 11 May 2022 © 2022. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".