Effects of filgotinib on semen parameters and sex hormones in male patients with inflammatory diseases: results from the phase 2, randomised, double-blind, placebo-controlled MANTA and MANTA-RAy studies.

The phase 2 MANTA and MANTA-RAy studies aimed to determine if the oral Janus kinase 1 preferential inhibitor filgotinib affects semen parameters and sex hormones in men with inflammatory diseases. MANTA (NCT03201445) and MANTA-RAy (NCT03926195) included men (21-65 years) with active inflammatory bowel disease (IBD) and rheumatic diseases (rheumatoid arthritis, spondyloarthritis or psoriatic arthritis), respectively. Eligible participants had semen parameters in the normal range per the WHO definition. In each study, participants were randomised 1:1 to receive once-daily, double-blind filgotinib 200 mg or placebo for 13 weeks for pooled analysis of the primary endpoint (proportion of participants with a ≥50% decrease from baseline in sperm concentration at week 13). Participants who met the primary endpoint were monitored over an additional 52 weeks for 'reversibility'. Secondary endpoints included change from baseline to week 13 in: sperm concentration, total motility, normal morphology, total count and ejaculate volume. Sex hormones (luteinising hormone, follicle stimulating hormone, inhibin B and total testosterone) and reversibility were exploratory endpoints. Across both studies, 631 patients were screened, and 248 were randomised to filgotinib 200 mg or placebo. Baseline demographics and characteristics were similar within indications between treatment groups. Numerically similar proportions of filgotinib-treated versus placebo-treated patients met the primary endpoint (8/120 (6.7%) vs 10/120 (8.3%)), Δ-1.7% (95% CI -9.3% to 5.8%)). There were no clinically relevant changes from baseline to week 13 in semen parameters or sex hormones, or patterns of reversibility between treatment groups. Filgotinib was well tolerated, with no new safety events. Results suggest that once daily filgotinib 200 mg for 13 weeks has no measurable impact on semen parameters or sex hormones in men with active IBD or inflammatory rheumatic diseases.

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Competing interests: WR has served as a speaker for AbbVie, Celltrion, Falk Pharma, Ferring, Janssen, Galapagos Medice, MSD, Roche, Pfizer, Pharmacosmos, Shire, Takeda, Therakos; as a consultant for AbbVie, Amgen, AOP Orphan, Arena Pharmaceuticals, Astellas, AstraZeneca, Bioclinica, Boehringer Ingelheim, Bristol Myers Squibb, Calyx, Celgene, Celltrion, Eli Lilly, Falk Pharma, Ferring, Galapagos, Gatehouse Bio, Genentech, Gilead, Grünenthal, ICON, Index Pharma, Inova, Janssen, Landos Biopharma, Medahead, MedImmune, Mitsubishi Tanabe Pharma Corporation, MSD, Novartis, OMass, Otsuka, Parexel, Periconsulting, Pharmacosmos, Pfizer, Protagonist, Provention, Quell Therapeutics, Sandoz, Seres Therapeutics, Setpointmedical, Sigmoid, Sublimity, Takeda, Teva Pharma, Therakos, Theravance, Zealand; as an advisory board member for AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Galapagos, Janssen, Mitsubishi Tanabe Pharma Corporation, MSD, Pharmacosmos, Pfizer, Sandoz, Takeda; and has received research funding from AbbVie, Janssen, MSD, Sandoz, Takeda. WH has been a consultant or adviser for Boston Scientific, Coloplast and Endo; has been an investigator for Coloplast and Endo; has been a lecturer for Endo; has been on advisory boards for Gilead Sciences, Maximus and Promescent; and is a board member, officer and trustee for Theralogix. RJEMD has received unrestricted research grants from the Dutch Arthritis Association, Galapagos and UCB; consulting fees from Galapagos; and speaking fees from AbbVie, Genzyme, Novartis, Lilly, Roche and UCB. SS declares no competing interests. RW has acted as a principal investigator, adviser and speaker for Celltrion, Galapagos and Gilead Sciences; and was an adviser for UCB. RMe declares no competing interests. TR has served on advisory boards or as a speaker for AbbVie, Arena Pharmaceuticals, Eli Lilly, Ferring Pharmaceuticals, Genentech, Gilead Sciences, Gossamer Bio, Intercept Pharmaceuticals, Janssen, Pfizer, Prometheus and Takeda. US has received grants from AbbVie, Abivax, Galapagos, Gilead Sciences, Index Pharmaceuticals, Janssen, Lilly, Roche-Genentech, Theravance Biopharma and Takeda; personal fees from AbbVie, Galapagos and Janssen; and non-financial support from Janssen and Galapagos. OGa declares no competing interests. VS declares no competing interests. OGo has served as a speaker for AbbVie, Amgen, Boehringer Ingelheim, Egis, Janssen, Johnson & Johnson, MSD, Novartis, Pfizer, Roche and Sandoz. SJ has received grants from Roche; consulting fees or honoraria from AbbVie,Amgen, Celgene, Lilly, Novartis, Roche, Sandoz, Sobi, UCB; and has been an advisory board member for Lilly, Novartis, Roche, Sandoz and Sobi. RMo declares no competing interests. VR, F-OLB and RB are employees and shareholders of Galapagos NV. TRW and SA are employees and shareholders of Gilead Sciences. DV received consultancy fees from Galapagos for the design and setup of the studies.