Improvement and Stabilization of Lung Function in Patients with SSc-ILD Treated with Nintedanib vs Placebo in a Randomized, Placebo-Controlled Phase III Trial: Proportions of Patients with FVC Changes Using Cutoffs Previously Proposed to Define Minimally Clinically Important Differences

Yannick Allanore¹, Dinesh Khanna ², Elizabeth Volkmann ³, Christian Stock ⁴, Martina Gahlemann ⁵, Nils Schoof ⁶, Oliver Distler ⁷ and Toby Maher ⁸, ¹Dept. of Rheumatology A, Descartes University, APHP, Cochin Hospital, Paris, France, Paris, France, ²Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA, Ann Arbor, ³University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, ⁴Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany, Ingelheim am Rhein, Germany, ⁵Boehringer Ingelheim (Schweiz) GmbH, Basel, Switzerland, Basel, Switzerland, ⁶Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany, ⁷Dept. of Rheumatology, University Hospital Zürich, Zürich, Switzerland, Zürich, Switzerland, ⁸National Heart and Lung Institute, Imperial College London, UK and National Institute for Health Research Clinical Research Facility, Royal Brompton Hospital, London, UK, London, United Kingdom

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: interstitial lung disease, outcome measures and lung, Systemic sclerosis

Session Information

Date: Sunday, November 10, 2019

Title: Systemic Sclerosis & Related Disorders – Clinical Poster I

Session Type: Poster Session (Sunday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Mean change in forced vital capacity percent predicted (FVC %pred) is a common endpoint in the assessment of treatment-related outcomes in patients with interstitial lung disease (ILD), including those with systemic sclerosis-associated ILD (SSc-ILD). However, it is important to determine the extent to which changes in FVC %pred for individual patients are clinically meaningful. In a previous analysis of two large randomized trials of cyclophosphamide versus placebo (Scleroderma Lung Study [SLS]-I) or versus mycophenolate mofetil (SLS-II) in patients with SSc-ILD, improvement in FVC %pred of ≥3% or deterioration of –3.3% were estimated to be the minimal clinically important differences (MCIDs) associated with statistically significant improvements or worsening in patient-reported outcomes, computer-assisted extent of fibrosis and total ILD (Kafaja et al. Am J Resp Crit Care Med 2018; 197:646–52). A Phase III randomized trial (SENSCIS®, NCT02597933) compared nintedanib 150 mg twice daily with placebo in patients with SSc-ILD, with the primary endpoint the annual rate of decline of FVC. In this analysis, we have assessed the proportions of patients with improvement, and stabilization or deterioration of disease after 1 year of treatment, according to the MCIDs established by Kafaja et al.

Methods: The SENSCIS® trial was a randomized, double-blind, placebo-controlled, parallel group trial conducted in 32 countries. Patients with SSc-ILD, defined as ≥10% lung fibrosis with a baseline FVC ≥40% predicted and DL_co of 30–89% predicted, were randomized 1:1 to receive oral nintedanib 150 mg twice daily or placebo. Background stable mycophenolate or methotrexate therapy was permitted. Spirometry (read and analyzed centrally) was conducted over 52 weeks. In this responder analysis, individual changes in FVC %pred from baseline at Week 52 were defined according to MCIDs defined for SLS-I and SLS-II as improvement (≥3% increase), stabilization (change between 3% and –3.3%) or deterioration (at least –3.3%).

Results: A total of 575 patients were included in the analysis, and baseline characteristics were comparable between treatment groups. An improvement in FVC %pred of ≥3% was observed after 52 weeks in 66/287 (23%) patients treated with nintedanib, and 43/288 (15%) who received placebo (OR 1.69; 95% CI 1.11–2.59; P=0.014) (Table). Significantly more patients in the nintedanib arm also experienced either an improvement or stabilization (66% vs 56%; OR 1.52; 95% CI 1.08–2.13; P=0.015) and significantly fewer patients in the nintedanib arm experienced deterioration (34% vs 44%; OR 0.66; 95% CI 0.47–0.92; P=0.015).

Conclusion: In patients with SSc-ILD, more patients treated with nintedanib than placebo experienced improvement in FVC %pred, and more experienced stabilization or improvement in FVC %pred, while fewer experienced deterioration, applying thresholds of clinical meaningfulness established in SLS-I and II, which included a similar patient population.

Minimal clinically importance difference in FVC Table

Number of patients who met or exceeded the MCID -from SLS I and II- for improvement, stabilization or deterioration in lung function over 52 weeks in patients with SSc-ILD participating in the SENSCIS® trial.

Disclosure: Y. Allanore, Actelion, 2, 5, Alpine, 2, 5, Bayer, 2, 5, BMS, 2, 5, Boehringer Ingelheim, 2, 5, Bristol Myers Squibb, 5, Bristol-Myers Squibb, 2, 5, Genentech Roche, 2, 5, Inventiva, 2, 5, Italfarmaco, 2, 5, Sanofi, 2, 5, Servier, 2, 5; D. Khanna, Acceleron, 5, 8, Acceleron Pharma, 5, Actelion, 5, 8, Actelion Pharmaceuticals, 5, Astra Zeneca, 5, Bayer, 2, 5, 8, Behring, 5, Blade, 5, Blade Therapeutics, 5, 8, Blade therapeutics, 5, BMS, 2, 5, 8, Boehringer Ingelham, 5, Boehringer Ingelheim, 5, 8, Boehringer-Ingelheim, 5, Bristol Myers Squibb, 2, 5, Bristol-Myers Squibb, 2, 5, Celegene, 5, Celgene, 5, 8, ChemomAB, 5, ChemomAb, 5, CiviBioPharma, Inc., 3, Corbus, 5, Corobus, 5, Corpus, 5, CSL Behring, 5, 8, Curizon, 5, Curzion, 5, Cytori, 5, 8, Eicos, 4, Eicos Sciences, 4, Eicos Sciences, Inc, 4, Eicos Sciences, Inc/ CiviBioPharma, Inc, 1, 4, Eicos Sciences, Inc/ CiviBioPharma, Inc., 1, Eicos, Inc, 4, Eicos, Inc., 5, 8, Eicos, INC., 4, Galapagos, 5, Genentech, 5, Genentech/Roche, 5, GlaxoSmithKline, 5, GSK, 5, Horizon, 2, 5, Mitsubishi Tanabe Pharma, 5, Mitsubishi Tanabe Pharma Dev America, 5, Mitsubishi Tanabe Pharma Development America, 5, Mitsubishi Tanabi, 5, NIH K24 and R01, 2, NIH / NIAMS K24 AR-063120, 2, NIH/NIAMS R01& K24, 2, Pfizer, 2, 5, Sanofi, 5, Sanofi Aventis, 5, Sanofi-Aventis, 5, 8, Sanofi-Aventis/Genzyme, 5, UCB, 5, UCB Pharma, 5; E. Volkmann, Boehringer Ingelheim, 5, Boehringer-Ingelheim, 5, Pfizer, 1, 4; C. Stock, Boehringer Ingelheim, 3; M. Gahlemann, Boehringer Ingelheim, 3; N. Schoof, Boehringer Ingelheim International GmbH, 3; O. Distler, A. Menarini, 5, Abbvie, Acceleron, 5, Acceleron Pharma, 5, Actelion, 2, 5, 8, Actelion Pharmaceuticals, 2, 5, 8, 9, Amgen, 5, AnaMar, 2, 5, Bayer, 2, 5, 8, 9, Biogen Idec, 2, 5, Blade Therapeutics, 5, Boehringer Ingelheim, 2, 5, 8, 9, Catenion, 5, 9, ChemomAb, 2, 5, ChemomAB, 5, CSL Behring, 5, Ergonex, 5, espeRare Foundation, 2, 5, Genentech/Roche, 2, 5, GlaxoSmithKline, 5, GSK, 2, 5, Holds Patent mir-29 for the treatment of systemic sclerosis, 9, Inventiva, 2, 5, iQvia, 5, Italfarmaco, 2, 5, Italfarmco, 5, Lilly, 2, 5, med, 5, 8, medac, 5, Medac, 2, 5, MedImmune, 2, 5, Medscape, 5, 8, 9, Menarini, 8, Mepha, 8, Mitsubishi Tanabe, 2, 5, Mitsubishi Tanabe Pharma, 2, 5, MSD, 5, 8, Novartis, 2, 5, 8, 9, Patent, 9, Patent issued, 9, Pfizer, 2, 5, 8, Pharmacyclics, 2, 5, Roche, 5, 8, 9, Sanofi, 2, 5, Sinoxa, 2, 5, Target Bio Science, 5, Target BioScience, 5, UCB, 2, 5, 9, UCB in the area of potential treatments of scleroderma and its complications, 2, 5; T. Maher, Boehringer Ingelheim, 5, 8.

To cite this abstract in AMA style:

Allanore Y, Khanna D, Volkmann E, Stock C, Gahlemann M, Schoof N, Distler O, Maher T. Improvement and Stabilization of Lung Function in Patients with SSc-ILD Treated with Nintedanib vs Placebo in a Randomized, Placebo-Controlled Phase III Trial: Proportions of Patients with FVC Changes Using Cutoffs Previously Proposed to Define Minimally Clinically Important Differences [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/improvement-and-stabilization-of-lung-function-in-patients-with-ssc-ild-treated-with-nintedanib-vs-placebo-in-a-randomized-placebo-controlled-phase-iii-trial-proportions-of-patients-with-fvc-changes/. Accessed .

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