An up-to-date review of approved and emerging antibody therapies for idiopathic pulmonary fibrosis

ABSTRACTIntroduction The use of pirfenidone and nintedanib in treating Idiopathic Pulmonary Fibrosis (IPF) has shown significant slowing down of the progressive functional decline in these patients. In recent times, antibody-based therapies with precise molecular targets have also been explored as alternative treatments to IPF.Areas covered This review aims to summarize the available updates regarding monoclonal antibodies that have been tested in IPF. The drugs describedare developed to antagonize inflammation,immunity pathways and fibrogenesis. Currently, the anti-CTGF pamrevlumab has demonstrated a significant reduction in functional decline as compared to placebo and is undergoing the last stages of phase 3 trial.Expert opinion Although antibody-based therapies for IPF have had unsatisfactory results in most trials in the last few years, the pursuit of therapeutic development in this field should continue to deliver a more personalized treatment approach in the future, which is currently not available with existing treatment options. However, several molecules are still under study and some have shown encouraging results in the early phases of clinical trials. Future investigations need to be more carefully designed and valid predictive markers of response to treatment should be used to enhance the effectiveness of future trials.KEYWORDS: Idiopathic pulmonary fibrosismonoclonal antibodiestargeted therapyprecision medicineInterstitial lung diseases Article highlights Nintedanib and pirfenidone, the two currently approved therapies for Idiopathic Pulmonary Fibrosis, reduce the rate of clinical and functional decline in these individuals without completely blocking the disease progression.Numerous antibody-based therapies aimed at mitigating both the pro-fibrotic and inflammation/immunity pathways have undergone randomized clinical trials (RCTs) over the past years. Some new molecules are currently in the early phases of investigation.Despite these efforts, the majority of RCTs involving antibody-based therapies have not managed to exhibit the effectiveness of the investigational drugs when compared to placebos.Pamrevlumab, an anti-CTGF monoclonal antibody, still stands out as the sole treatment demonstrating efficacy compared to a placebo in IPF patients. It is currently under investigation in the last stages of a phase 3 RCT.A precise categorization of the disease, using predictive indicators of response to novel targeted interventions, has become a crucial need. This necessity aims to enhance the efficacy of future RCTs and personalized therapy in IPF."Declaration of interestG Sgalla reports fees from Boehringer Ingelheim outside the submitted work. L Richeldi has received grants and personal fees from Boehringer Ingelheim and InterMune, and personal fees from Biogen-Idec, ImmuneWorks, Medimmune, Roche, Sanofi-Aventis, Shionogi, and Takeda outside of the submitted work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Reviewer disclosuresPeer reviewers on this manuscript have no relevant financial or other relationships to disclose.Additional informationFundingThis paper was not funded.