Results of INBUILD trial on the safety and efficacy of nintedanib for RA-ILD patients

The standard of therapy for rheumatoid arthritis (RA) is disease-modifying anti-rheumatic drugs (DMARDs) and glucocorticoids, but there is no proof from randomized controlled studies that they delay the development of pulmonary fibrosis. Idiopathic pulmonary fibrosis (IPF), fibrosing ILD linked to systemic sclerosis (SSc), and progressive fibrosing ILDs of any aetiology are all conditions that can be treated with nintedanib, a tyrosine kinase inhibitor. Now, a recent study published in Clinical Rheumatology has reported the slow decline in forced vital capacity (FVC) in patients with progressive RA-ILD patients. Besides, the safety and efficacy of using nintedanib in these patients were reported to be consistent between patients taking DMARDs and glucocorticoids at baseline.

Dr. Matteson and his team have conducted a randomized, double-blind, placebo-controlled trial named, INBUILD trial to assess the safety and efficacy of nintedanib in progressive RA-LD patients. After 52 weeks of nintedanib treatment, 89/663 patients with RA-ILD reported a rate of decline in FVC as –82.6 mL/year compared to placebo with –199.3 mL/year. Experts observed diarrhea to be the common adverse event reported among 61.9% and 27.7% in the study ad control groups. The occurrence of adverse events has resulted in discontinuation of the treatment in 23.8% and 17.0% of the patients in both groups. Thus, the rate of FVC declined in RA-ILD patients with the use of the nintedanib drug. 

A similar INBUILD trial conducted in 2020 predicted FVC ≤50%, 50%–≤70%, and >70% in 314, 274, and 75 patients with RA-ILD. After 52 weeks, the mean rate of decline in FVC was greater in patients with FVC ≤50% than in the other groups at baseline. However, the treatment-by-subgroup-by-time interaction p-value did not show a differential treatment effect of nintedanib across the subgroups by FVC% predicted (p=0.75). Instead, it showed that the effect of nintedanib vs placebo on slowing the rate of decline in FVC was numerically more pronounced in subjects with FVC >70% predicted at baseline. 

Thus, nintedanib was proven to slow down the FVC rate in patients with progressive fibrosing ILDs without considering their degree of FVC impairment at baseline. In collaboration with pulmonology colleagues and other relevant providers, rheumatologists must be aware of the risk factors for ILD, use wise assessment strategies that can help identify patients with ILD, monitor for ILD progression, and develop an effective treatment plan for patients with ILD.

References

  1. Matteson EL, Aringer M, Burmester GR. Mueller H,  Moros L and Kolb M. Effect of nintedanib in patients with progressive pulmonary fibrosis associated with rheumatoid arthritis: data from the INBUILD trial. Clin Rheumatol (2023). https://doi.org/10.1007/s10067-023-06623-7
  2. Valenzuela C, Maher TM, Bonella F, Pesci A, Jouneau S, Patel NM, Pérez ER, Goeldner RG, Stowasser S, Schlenker-Herceg R, Quaresma M. Effects of nintedanib in patients with progressive fibrosing ILDs and differing baseline FVC: further analyses of the INBUILD trial. https://erj.ersjournals.com/content/56/suppl_64/4577
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