POS1246 EFFECTS OF NINTEDANIB IN PATIENTS WITH SYSTEMIC SCLEROSIS-ASSOCIATED INTERSTITIAL LUNG DISEASE (SSC-ILD) IN SUBGROUPS BY DISEASE ACTIVITY INDEX

• Published in: Annals of the rheumatic diseases Vol. 82; no. Suppl 1; p. 963
• Main Authors: Herrick, A, Pope, J, Carreira, P, Miede, C, Alves, M, Allanore, Y
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.06.2023
• Subjects: Adverse events; C-reactive protein; Carbon monoxide; Clinical trials; Computed tomography; Cough; Diarrhea; DNA topoisomerase; Fibrosis; Lung diseases; Mycophenolic acid; Patients; Pharmaceuticals; Placebos; Respiratory tract diseases; Rhinopharyngitis; Scleroderma; Systemic sclerosis; Ulcers; Vomiting
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2023-eular.2262

BackgroundThe European Scleroderma Trials and Research group (EUSTAR) disease activity index was developed to assess disease activity in patients with systemic sclerosis (SSc).ObjectivesTo assess disease activity using a modified version of the EUSTAR disease activity index, and compare outcomes in subgroups by disease activity, in patients with SSc-ILD in the SENSCIS trial of nintedanib versus placebo.MethodsThe SENSCIS trial enrolled patients with SSc with first non-Raynaud symptom in the prior ≤7 years and extent of fibrotic ILD on high-resolution computed tomography (HRCT) ≥10%. Patients were randomised to receive nintedanib or placebo. The EUSTAR disease activity index assesses SSc activity based on modified Rodnan skin score (mRSS), C-reactive protein (CRP) level, diffusing capacity of the lung for carbon monoxide (DLco), presence of digital ulcers, presence of tendon friction rubs, and worsening of skin fibrosis over the previous month (as assessed by the patient). A score ≥2.5 identifies patients with active/very active vs inactive/moderately active disease. For this analysis, a modified version of the index was developed that excluded worsening of skin fibrosis, as data prior to enrolment in the trial were not collected. The modified version had a maximum score of 8.5. We analysed the rate of decline in FVC (mL/year) and adverse events over 52 weeks in subgroups by score on the modified index (<2.5 or ≥2.5) at baseline. An exploratory interaction p-value was calculated to assess potential heterogeneity in the effect of nintedanib versus placebo between the subgroups.ResultsAmong 523 patients, 55.1% and 44.9% had modified disease activity index scores of <2.5 and ≥2.5, respectively at baseline. Compared with patients with a score <2.5, those with a score ≥2.5 had a greater extent of fibrosis on HRCT (38.0% vs 34.8%) and lower mean FVC % predicted (69.1 vs 75.1); greater proportions had diffuse cutaneous SSc (70.2% vs 38.9%), were anti-topoisomerase I antibody positive (65.5% vs 56.3%) and were taking mycophenolate (54.0% vs 45.8%). In the placebo group, the rate of decline in FVC over 52 weeks was numerically greater in patients with a score ≥2.5 than <2.5 (Figure 1). The effect of nintedanib on reducing the rate of FVC decline was numerically greater in patients with a score ≥2.5 than <2.5, but the interaction p-value did not indicate heterogeneity in the effect of nintedanib between the subgroups (p=0.24). The adverse event profile of nintedanib was similar between the subgroups (Table 1).ConclusionBased on a modified version of the EUSTAR disease activity index, almost half of the patients in the SENSCIS trial had active/very active SSc. Nintedanib had a consistent effect on reducing the rate of FVC decline over 52 weeks in patients with low and high SSc disease activity at baseline.Figure 1.Rate of decline in FVC (mL/year) over 52 weeks in subgroups by modified disease activity index at baseline in the SENSCIS trial[Figure omitted. See PDF]Table 1.Adverse events in the SENSCIS trial in subgroups by modified disease activity index at baseline.Score <2.5Score ≥2.5Nintedanib (n=146)Placebo (n=142)Nintedanib (n=121)Placebo (n=114)Most frequent adverse events*Diarrhoea78.827.571.133.3Nausea30.815.535.512.3Skin ulcer13.711.324.026.3Vomiting22.69.228.912.3Cough12.313.49.920.2Nasopharyngitis17.118.39.116.7Upper respiratory tract infection6.810.613.28.8Abdominal pain8.99.211.63.5Fatigue9.66.314.09.6Weight decreased11.05.612.43.5Adverse event(s) leading to treatment discontinuation17.89.914.08.8*Adverse events were coded according to preferred terms in the Medical Dictionary for Regulatory Activities (MedDRA). Data are % of patients with ≥1 such adverse event reported over 52 weeks (or until 28 days after last trial drug intake in patients who discontinued trial drug before week 52). Adverse events reported in >10% of patients in either treatment group in the overall trial population are shown. AcknowledgementsThe SENSCIS trial was supported by Boehringer Ingelheim International GmbH.Disclosure of InterestsAriane Herrick Speakers bureau: Janssen, Actelion, Consultant of: Arena Pharmaceuticals, Boehringer Ingelheim, Camurus, CSL Behring, Galderma, Gesynta Pharma, Grant/research support from: Actelion, Gesynta Pharma, Janet Pope: None declared, Patricia Carreira Speakers bureau: Boehringer Ingelheim, Roche, Paid instructor for: Boehringer Ingelheim, Mitsubishi Tanabe, Consultant of: Boehringer Ingelheim, Emerald Health Pharmaceuticals, Mitsubishi Tanabe, Sanofi-Genzyme, Janssen, GlaxoSmithKline, Grant/research support from: Janssen, Roche, Corinna Miede Employee of: Employee of mainanalytics GmbH, Sulzbach (Taunus), Germany, which was contracted by Boehringer Ingelheim to assist with these analyses, Margarida Alves Employee of: Employee of Boehringer Ingelheim, Yannick Allanore Consultant of: Boehringer Ingelheim, AstraZeneca, Prometheus, Galderma, Janssen, Medsenic, AbbVie, Grant/research support from: Alpine Immune Sciences, Medsenic, Corvus Pharmaceuticals.