COMBINATION THERAPY WITH PIRFENIDONE AND NINTEDANIB IN IDIOPATHIC PULMONARY FIBROSIS: A SYSTEMATIC REVIEW AND META-ANALYSIS

SESSION TITLE: Diffuse Lung Disease: Medications; Is It the Problem or the Solution? SESSION TYPE: Original Investigations PRESENTED ON: 10/09/2023 08:30 am - 09:30 am PURPOSE: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung disease. Nintedanib and pirfenidone are anti-fibrotic medications that have been shown to slow the decline in forced vital capacity (FVC) in IPF. However, literature evaluating the use of nintedanib and pirfenidone together as “combination therapy” is sparse. METHODS: A systematic search based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed on three databases (Pubmed, Embase, and Web of Science). Studies evaluating the use of nintedanib with pirfenidone (“combination therapy”) among patients diagnosed with IPF were included. Adverse events (AE) were events related to anti-fibrotic therapy. Serious AEs were AEs that were life-threatening, requiring hospitalization, or resulting in death/disability. Statistical analysis was performed using Stata 17.0 (College Station, Texas). RESULTS: Seven studies involving a total of 238 patients (78.8% males) receiving combination therapy with nintedanib (200-300 mg/day) and pirfenidone (600-2400 mg/day) were identified. The mean age was 68.2 years (SD 7.1). The average duration of combination therapy was 4.5 months (range 0.75-6) with patients being followed for an average duration of 7.5 months (range 1-14). Participants had a mean DLCO of 48.2% predicted [95% CI 45.2-51.2], and a mean FVC of 71.3% predicted [95% CI 64.1-78.5]. Among those receiving combination therapy, 79% [95% CI 70-88] experienced an AE, 25% [95% CI 13-36] experienced an AE leading to discontinuation of therapy, and 6% [95% CI 1-10] experienced a serious AE. Diarrhea (41%), nausea (35%), vomiting (21.5%), loss of appetite (19.2%), fatigue (15%), elevated liver enzymes (8%), and photosensitivity (7%) were common AEs. Of those discontinuing therapy due to AEs, the most common cause was diarrhea (31%). In studies comparing anti-fibrotic monotherapy with combination therapy, participants experiencing an AE was 80% [95% CI 57-92] in monotherapy versus 79% [95% CI 55-92] in combination therapy. 10% [95% CI 4-21] of monotherapy versus 34% [95% CI 21-50] receiving combination therapy experienced an AE leading to discontinuation of therapy (p=0.001). 8% [95% CI 4-17] of monotherapy versus 5% [95% CI 2-13] of combination therapy experienced a serious AE. Studies assessing the exploratory efficacy demonstrated a trend toward decreased rate of FVC decline (statistically significant in two out of five studies) among patients receiving combination therapy compared to monotherapy. CONCLUSIONS: Combination therapy demonstrated an adverse effect profile similar to that of monotherapy with pirfenidone or nintedanib. Gastrointestinal AEs predominated with diarrhea being the most common AE leading to discontinuation of therapy. Limited data on exploratory efficacy suggest a potential benefit of combination therapy over monotherapy in slowing the decline of FVC. CLINICAL IMPLICATIONS: Combination therapy with nintedanib and pirfenidone may present as a viable therapeutic strategy for patients with IPF with limited data regarding safety and efficacy. Existing literature indicates that combination therapy is well tolerated with a safety profile similar to that of monotherapy and may also favorably slow the decline of FVC. However, there is a need for larger clinical trials assessing the long-term safety and efficacy of this approach. DISCLOSURES: No relevant relationships by Tanmay Gandhi No relevant relationships by Emily Kocurek No relevant relationships by PRACHI SALUJA No relevant relationships by Aniruddh Shah