GI Symptom Severity after Nintedanib Treatment for Systemic Sclerosis–Associated Lung Disease

According to data from the SENSCIS-ON trial, presented at the American College of Rheumatology (ACR) Convergence 2021, patients with systemic sclerosis–associated interstitial lung disease (SSc-ILD) reported a worsening of gastrointestinal (GI) adverse events over one year treatment with nintedanib, which may impact quality of life.

“Gastrointestinal (GI) involvement is a common manifestation of SSc and a frequent side-effect of drugs used to treat SSc,” wrote the study authors.

This study analyzed data from SENSCIS-ON, the open-label extension of the SENSCIS trial, which evaluated nintedanib for treatment of SSc-ILD. “In the SENSCIS trial, nintedanib reduced the rate of decline in forced vital capacity (FVC) in patients with SSc-ILD, with an adverse event profile characterized predominantly by GI events,” the authors explained. The goal of this analysis was to assess the severity and impact on quality of life of these GI events among patients enrolled in SENSCIS-ON.

For this analysis patients were separated into two groups, the first of which was the “continued nintedanib” group, comprising 197 patients who received up to 100 weeks of nintedanib in SENSCIS and continued their regimen in SENSCIS-ON. The “initiated nintedanib” group included 247 patients who received placebo in SENSCIS and began treatment with nintedanib in SENSCIS-ON.

The primary outcome was change in scores on the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT) version two questionnaire from baseline through week 52. The UCLS SCTC GIT questionnaire assesses severity and impact of GI symptoms across seven scales: reflux, distension or bloating, fecal soilage, diarrhea, constipation, emotional well-being, and social functioning. Total scores range from 0 to 2.83, with higher scores meaning worse symptoms.

At baseline, 178 and 218 patients in the continued and initiated groups, respectively, had UCLA SCTC GIT scores. The mean baseline scores were 0.33 in both groups. Mean scores on individual scales ranged from 0.16 to 0.70 in the continued nintedanib group and from 0.13 to 0.64 in the initiated nintedanib group. Both groups demonstrated worsening GI symptoms over the course of the analysis period, expect for constipation symptoms.

By week 52, 45.7% and 39.7% of patients in the continued and initiated treatment groups had no or mild GI symptoms. However, the overall proportion of patients with moderate, severe, or very severe GI symptoms increased from baseline levels.

The researchers noted that diarrhea symptoms had the greatest impact on patients’ quality of life scores. These data were in line with previous safety profiles for nintedanib.

“In the SENSCIS-ON trial, the majority of patients with SSc-ILD treated with nintedanib had no or mild GI symptoms at baseline,” the researchers concluded. “A small worsening in GI symptoms was observed over 52 weeks. Diarrhea had the greatest impact, reflecting the adverse event profile of nintedanib. Recommendations for the management of diarrhea in patients treated with nintedanib should be implemented in clinical practice.”