Appropriateness of small molecule agents for patients with IBD of childbearing age - a RAND/UCLA appropriateness panel.

Background: Many women of childbearing age with inflammatory bowel disease (IBD) require advanced therapies. While biologics are largely low risk during pregnancy, the novel small molecules tofacitinib, filgotinib, upadacitinib and ozanimod (TFUO) have shown concerning teratogenic effects, and decreased fertility in animal studies. Therefore, their use in women of childbearing age needs careful consideration.
Design: RAND/University of California Los Angeles (UCLA) Appropriateness Method (RAM).
Objective: To evaluate the appropriateness of TFUO in women of childbearing age.
Methods: We convened a panel of six gastroenterologists, two IBD nurses, one IBD pharmacist and three expert patients. Following a literature review, 13 statements were drafted and voted upon in 2 rounds.
Results: All 13 statements were deemed appropriate. The panel concluded that women with IBD of childbearing age who wish to commence therapy with TFUO, need to use effective contraception and be counselled regarding the risk in unplanned pregnancies. For women using contraception while on Janus kinase inhibitor (JAKi) therapy, we suggest the preferred use of progesterone-only or non-hormonal long-acting contraception. TFUO are contraindicated during pregnancy and breast feeding. We recommend that women receiving TFUO cease therapy in time to establish clinical remission for at least 3 months prior to conception. Therapies other than TFUO should be considered as first-line therapy in women with IBD of childbearing age, except in select individual circumstances. TFUO may be appropriate for women of childbearing age after failure of, intolerance or contraindications to one biological agent.
Conclusion: TFUO should be avoided during pregnancy and breastfeeding, and alternative therapies should be considered as first-line treatments.
Summary: We provide clinical practice recommendations regarding the use of TFUO for IBD in women of childbearing age.
Competing Interests: C.P.S. has received unrestricted research grants from Warner Chilcott, Janssen, Galapagos and AbbVie, has provided consultancy to Warner Chilcott, Dr Falk, AbbVie, Takeda, Fresenius Kabi, Eli Lilly, Galapagos, Ferring, Arena and Janssen, and had speaker arrangements with Warner Chilcott, Dr Falk, Galapagos, AbbVie, MSD, Pfizer, Eli Lilly, BMS, UCB, Fresenius Kabi, Celltrion and Takeda. A.K. has provided consultancy to AbbVie, Galapagos, Ferring, Warner Chilcott and Janssen and had speakers fees from AbbVie, Galapagos, Janssen, Takeda and Falk. K.K. has provided consultancy to AbbVie and Galapagos, and had speaker arrangements with AbbVie, Galapagos, Janssen and Ferring. J.L. has provided consultancy to AbbVie, Arena, BioHit, Bristol Myers Squibb, Eli Lilly, Galapagos, Janssen, Pfizer and Takeda; has received speaker fees from to AbbVie, BioHit, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Galapagos, Janssen, MSD, Pfizer, Takeda; and research grants from Galapagos and Takeda. A.F. has provided consultancy to Warner Chilcott, Dr Falk, AbbVie, Takeda, Allergan, Galapagos, Ferring, Pharmacosmos, UCB, Bristol Myers Sqibb and Janssen, and had speaker arrangements with Warner Chilcott, Allergan, Dr Falk, Galapagos, AbbVie, Pfizer, Ferring, Pharmacosmos, Bristol Myers Squibb, Fresenius Kabi, Celltrion and Takeda. F.R. has provided consultancy to Bristol Myers Squibb, Celltrion and Takeda and had speaker arrangements with Dr Falk, Ferring, Gilead, Intercept and Pfizer. The other authors have no conflict of interests to disclose.
(© The Author(s), 2024.)