Patients with IPF and multiple comorbidities experienced similar effects from nintedanib to those with few or no comorbidities.
Ian Glaspole, MBBS, PhD
Findings in a new study showed that nintedanib, an approved treatment for idiopathic pulmonary fibrosis (IPF), had a similar benefit for both patients with and without a multitude of comorbidities. However, investigators also noted a greater rate of discontinuation due to adverse events among patients with more comorbidities.
This highlights the necessity of identifying and treating comorbidities during management of IPF.
A team, led by Ian Glaspole, MBBS, PhD, and funded by Boehringer Ingelheim, assessed the efficacy and safety of nintedanib in patients with IPF and additional comorbidities. The findings were presented earlier last week during the American Thoracic Society (ATS) 2020 Virtual Sessions.
Nintedanib has proven beneficial for patients with IPF by reducing decline in forced vital capacity (FVC).
The investigators collected their data from 5 placebo-controlled clinical trials: the phase 2 TOMORROW trial (52 weeks), the 2 phase 3 INPULSIS trials (52 weeks), the INMARK trial (12 weeks) and a phase 3b trial (approximately 6 months).
All IFP cases were divided into 2 subgroups: patients with ≥5 comorbidities (n = 847) and <5 comorbidities (n = 843) at baseline.
Both subgroups were assessed in annual rate of decline in FVC (mL/year), change from baseline in St. George’s Respiratory Questionnaire (SGRQ) total score, time to first acute exacerbation, time to death, and adverse events.
The most common comorbidity in both groups was hypertension, with 58% attributed to patients in the ≥5 comorbidities subgroup (vs 28% in the <5 subgroup). More frequent comorbidities in the ≥5 subgroup were gastroesophageal reflux disease (GERD) (39%), hypercholesterolemia (22%), osteoarthritis (21%), and hyperlipidemia (18%).
The frequent comorbidities in the <5 subgroup were diabetes (19%), GERD (10%), hypercholesterolemia (7%), and benign prostatic hyperplasia (6%).
Investigators noted that the mean exposure to the drug and placebo was 8.8 and 8.2 months for patients with ≥5 comorbidities, respectively. For the <5 subgroup, exposure was 9.2 and 8.1 months, respectively.
Results from the SGRQ over 52 weeks showed that patients in the ≥5 subgroup, especially those who received placebo, reported higher (worse) scores than those in the <5 subgroup. The difference in scores between treatment groups for the <5 subgroup was -0.8 (95% CI, -3.3 to 1.8), versus -3.0 (95% CI, -5.6 to -0.5) for the ≥5 subgroup.
Glaspole and colleagues indicated that the adverse event profiles between both subgroups were similar. Diarrhea and nausea were more common in the ≥5 subgroup than the <5 subgroup (65.5% diarrhea and 54.0% nausea vs 26.5% and 12.0%, respectively).
They also found that nintedanib reduced the annual rate of FVC decline in both subgroups; according to the study, there was no significant difference in treatment effect. Additionally, the results for treatment and placebo groups for time to first acute exacerbation, as well as time to death, were consistent between both subgroups.
Finally, 20.5% of nintedanib patients with ≥5 comorbidities experienced adverse events that led to discontinuation of treatment—compared to 12.1% of placebo patients. In patients with <5 comorbidities, 15.7% discontinued treatment as a result of adverse events—compared to 10.0% of placebo patients.
The most common adverse event between both subgroups for those receiving nintedanib was diarrhea.
“The presence of comorbidities may influence decisions about the use of antifibrotic therapy,” Glaspole and team stressed.
The study, “Efficacy and safety of nintedanib in patients with idiopathic pulmonary fibrosis (IPF) and multiple comorbidities,” was presented at ATS 2020.