A recent study published in Rheumatology (Oxford) has demonstrated the positive effects of nintedanib in slowing the decline of lung function in patients with limited cutaneous systemic sclerosis (lcSSc) and interstitial lung disease (ILD). This research is part of the Safety and Efficacy of Nintedanib in Systemic SClerosIS (SENSCIS) trial, which aimed to investigate the progression of ILD and the efficacy of nintedanib in this patient population. The SENSCIS trial involved patients with systemic sclerosis-related interstitial lung disease (SSc-ILD) who were randomly assigned to receive either nintedanib or a placebo. Participants who completed the initial phase of the trial were given the option to enter SENSCIS-ON, an open-label extension study where all patients received nintedanib.
Among the 277 patients with lcSSc who participated in the SENSCIS trial, those in the placebo group experienced an average decline in forced vital capacity (FVC) of 74.5 ml per year. In contrast, patients receiving nintedanib showed a slower decline, with an average FVC reduction of 49.1 ml per year. The difference between the two groups was 25.3 ml per year, suggesting a significant benefit from nintedanib treatment. At the 52-week mark, data from 249 patients indicated that the mean change in FVC was -86.4 ml in the placebo group compared to -39.1 ml in the nintedanib group. These results reinforce the potential of nintedanib in mitigating lung function deterioration in lcSSc patients.
Further, the SENSCIS-ON study provided additional insights. Among 183 lcSSc patients who transitioned to SENSCIS-ON, those previously on placebo and then started on nintedanib showed an FVC decline of 41.5 ml over 52 weeks. Conversely, patients who continued nintedanib treatment from the original SENSCIS trial experienced a similar FVC decline of 45.1 ml over the same period. In the SENSCIS trial study by Allanore et al; nintedanib was found to significantly slow the annual decline in FVC in patients with ILD associated with systemic sclerosis. Among the 576 patients studied, those receiving nintedanib showed an adjusted annual FVC decline of -52.4 ml, compared to -93.3 ml in the placebo group, marking a difference of 41.0 ml per year (P = 0.04).
Nintedanib is a small molecule that inhibits multiple tyrosine kinases, including the receptors for platelet-derived growth factor (PDGF) αβ, fibroblast growth factor (FGF) 1–3, and vascular endothelial growth factor (VEGF). Additionally, it targets Fms-like tyrosine-protein kinase, lymphocyte-specific tyrosine-protein kinases Lck and Lyn, proto-oncogene tyrosine-protein kinase Src, and colony-stimulating factor-1 receptor. By competitively binding to the ATP pocket of these kinases, nintedanib effectively blocks intracellular signaling cascades, impeding the pathways that contribute to disease progression.
In September 2019, the FDA approved the use of nintedanib for systemic sclerosis-associated interstitial lung disease (SSc-ILD), with the EMA following in April 2020. Additionally, in March 2020, the FDA approved nintedanib for chronic fibrosing interstitial lung diseases with a progressive phenotype (PF-ILD), with the EMA granting approval in July 2020. These approvals were based on significant clinical trials, including the INPULSIS, SENSCIS, and INBUILD trials, which demonstrated the drug’s efficacy in slowing lung function decline and managing disease progression in these conditions.
The findings from the SENSCIS and SENSCIS-ON trials highlight the effectiveness of nintedanib in targeting pulmonary fibrosis and slowing the decline in lung function among patients with lcSSc and ILD. This promising development offers hope for improved management and outcomes for those affected by this challenging condition.
Reference
- Allanore Y, Khanna D, Smith V, Aringer M, Hoffmann-Vold AM, Kuwana M et al. SENSCIS Trial Investigators. Effects of nintedanib in patients with limited cutaneous systemic sclerosis and interstitial lung disease. Rheumatology (Oxford). 2024 Mar 1;63(3):639-647.
- Distler O, Highland KB, Gahlemann M, Azuma A, Fischer A, Mayes MD, et a. SENSCIS Trial Investigators. Nintedanib for Systemic Sclerosis-Associated Interstitial Lung Disease. N Engl J Med. 2019 Jun 27;380(26):2518-2528.
- Kuwana M, Azuma A. Nintedanib: New indication for systemic sclerosis-associated interstitial lung disease. Mod Rheumatol. 2020 Mar;30(2):225-231.