Sex of Patients With ILD Should Be Considered When Managing Nintedanib-Related Adverse Events

Although the adverse event (AE) profile of nintedanib was generally similar between men and women with autoimmune disease-related interstitial lung diseases (ILDs), patients’ sex should be considered in the monitoring and management of AEs related to treatment with nintedanib, according to findings from a post hoc analysis published in The Lancet Rheumatology. 

The researchers sought to evaluate the safety and tolerability of the tyrosine kinase inhibitor nintedanib in patients with autoimmune disease-related ILDs and nonautoimmune disease-related ILDs (ie, other ILDs), according to sex.

Researchers assessed the AEs reported over a 52-week period in the subgroups of individuals, with data on sex collected from case report forms.

Data were pooled from the 2 INPULSIS trials (ClinicalTrials.gov Identifiers: NCT01335464 and NCT01335477) in patients with idiopathic pulmonary fibrosis (IPF), the SENSCIS trial (ClinicalTrials.gov Identifier: NCT02597933) in patients with fibrosing ILDs associated with systemic sclerosis (SSc), and the INBUILD trial (ClinicalTrials.gov Identifier: NCT02999178) in patients with progressive fibrosing ILDs other than IPF.

In each of the trials, participants were randomly assigned to receive treatment with oral nintedanib 150 mg twice daily or matched placebo. The post hoc analyses were descriptive and included patients who received at least 1 dose of nintedanib.

• In the INPULSIS trials, 79% of the treated patients were men and 21% were women, of whom 21% of men and 25% of women discontinued the trial medication prior to week 52.
• In the SENSCIS trial, 25% of the treated patients were men and 75% were women, of whom 12% of men and 16% of women discontinued the study medication before week 52.
• In the INBUILD trial, 54% of the treated patients were men and 46% were women, of whom 19% of men and 20% of women discontinued the trial medication prior to week 52.

The pooled data set of patients with autoimmune disease-related ILDs included 746 individuals, of whom 70% were women. A total of 82% in this subgroup had SSc-associated ILD. Women had a lower mean body weight, lower forced vital capacity (FVC), and greater % predicted mean diffusing capacity of the lungs for carbon monoxide (DLCO). Further, a small percentage of women vs men were receiving treatment with corticosteroids.

The pooled datatset of patients with other ILDs included a total of 1554 individuals, of whom 28% were women. Among the patients in this subgroup, 68% had IPF. Women vs men had a lower mean body weight and lower FVC; a higher percentage of men were receiving treatment with corticosteroids.

Overall, patients with autoimmune disease-related ILDs compared with those with other ILDs were younger, had lower body mass index (BMI), lower % predicted FVC, higher % predicted DLCO (women), and were more likely to be receiving treatment with corticosteroids (men).

Among patients with autoimmune disease-related ILDs, the median exposure to the trial drug (regardless of whether the dose of nintedanib was reduced) was 12.2 months (minimum to maximum, 0.0-12.2 months) in the nintedanib group and 12.2 months (minimum to maximum, 0.4-12.2 months) in the placebo group among men. Corresponding values among women were 12.2 months (minimum to maximum, 0.0-12.2 months) in the nintedanib group and 12.2 months (minimum to maximum, 0.3- 12.2 months) in the placebo group.

Among the participants with other ILDs, the median exposure to the trial drug  (regardless of whether the dose of nintedanib was reduced) was 11.9 months (minimum to maximum, 0.0-12.5 months) in the nintedanib group and 11.9 months (minimum to maximum, 0.0-13.1 months) in the placebo group among men. Corresponding values among women were 11.9 months (minimum to maximum, 0.0-12.7 months) in the nintedanib group and 12.1 months (minimum to maximum, 0.2-12.8 months) in the placebo group.

Among patients with autoimmune disease-related ILDs, the AE profile of nintedanib was generally similar between men and women, although the occurrence of nausea, vomiting, elevations in liver enzymes, dose reductions, and treatment interruptions were more common among women vs men. Observations were similar among participants with other ILDs.

Several limitations of the current analysis should be noted. The group of participants with autoimmune disease-related ILDs predominantly included individuals with SSc-associated ILD, whereas most of the patients with other ILDs had IPF. Therefore, these populations should not be considered representative of patients with autoimmune disease-related ILDs and other ILDs. Further, the analyses were based on data from only 1 year of treatment, with the trials differing in the co-medications that were used.

The investigators emphasized the importance of shared decision-making between patient and provider. They concluded, “Sex should be considered in patient education and in the monitoring and management of [AEs] that might be associated with nintedanib.”

Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Hoffmann-Vold A-M, Volkmann ER, Allanore Y, et al. Safety and tolerability of nintedanib in patients with interstitial lung diseases in subgroups by sex: a post-hoc analysis of pooled data from four randomised controlled trials. Lancet Rheumatol. 2022;4(10):e679-e687. doi:10.1016/S2665-9913(22)00215-6