Background/Purpose: Nintedanib slows the progression of systemic sclerosis-associated interstitial lung disease (SSc-ILD). However, potential high discontinuation rates due to adverse side-effects raise concerns about its tolerability in this patient group.

Methods: In this multicenter study, nintedanib tolerability and body weight changes were assessed. Nintedanib interruption was defined as any interruptions due to treatment-related side effects. Predictors of nintedanib interruption were assessed using logistic regression, with multivariable analysis adjusting for potential confounders. Fisher’s exact test was used when complete separation precluded logistic regression and time to first treatment interruption was analysed by Cox proportional hazards analysis. The Wilcoxon signed-rank test was used to compare body weight changes before and after nintedanib initiation.

Results: Among 63 patients (mean age 56.5±13.8 years, 22% male and 56% ever smokers), 76.2% received nintedanib 150 mg twice daily, the remainder 100 mg twice daily. Both concomitant mycophenolate mofetil use and baseline gastrointestinal (GI) symptoms were reported in 85.7% of patients. Patient-reported GI symptoms included diarrhoea (58.7%, 41.3% requiring loperamide), reflux (47.6%), weight loss (38.1%), and nausea/vomiting (33.3%). Over a median follow up of 22.2 months (95% CI 18.1-26.2), Nintedanib was interrupted in 50.8% of patients. Older age (p < 0.03 on univariable and multivariable analyses) and BMI 18.5 kg/m2 (p = 0.024) were significant predictors of interruption. Patients with BMI 18.5 kg/m2 had a significantly shorter time to treatment interruption compared to those with higher BMI (Figure 1) and remained significant after adjustment for FVC or DLCO and demographic variables. Baseline GI symptoms and concurrent Disease-Modifying Antirheumatic Drugs used were not associated with interruption. Most patients who experienced interruption were able to restart treatment, either at reduced or full dose. Permanent discontinuation occurred in 22.2%, with no significant risk factors identified. Mean weight loss over 12 (±6)months after initiation was 1.93 kg (95% CI: 0.64-3.22, p=0.0041), significantly greater than in the 12 (±6)months before treatment (1.38 kg) (p=0.0008).

Conclusion: Among patients with SSc-ILD treated with nintedanib, adverse effects and weight loss frequently led to treatment interruptions. Older age and lower BMI were significant predictors of interruption, while no clear predictors of permanent discontinuation were identified, such as baseline GI symptoms, larger studies are needed to confirm these findings. Most patients were able to resume treatment, underscoring the need for close monitoring and accessible healthcare professional support.

Figure 1 Smoothed representation of the Kaplan-Meier survival curve showing the proportion of patients remaining on uninterrupted treatment over time, stratified by body mass index (BMI) ( < 18.5 vs ≥18.5 kg/m²). The dashed line represents patients with BMI < 18.5 kg/m²; the solid line represents patients with ≥18.5 kg/m². Shaded areas represent the 95% Confidence Interval (C.I).

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/nintedanib-in-systemic-sclerosis-associated-interstitial-lung-disease-real-world-cohort-study-on-tolerability-and-discontinuation/