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. 2024 Nov 13:17:17562848241299737.
doi: 10.1177/17562848241299737. eCollection 2024.

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

Christian Selinger  1 , Robyn Laube  2 , Jimmy K Limdi  3 , Kate Headley  4 , Alexandra Kent  5 , Klaartje Kok  6 , Aileen Fraser  7 , Victoria Newman  8 , Helen Ludlow  9 , Fiona Rees  10 , Nidhi Sagar  11 , Erin Walker  4
Affiliations

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

Christian Selinger et al. Therap Adv Gastroenterol. .

Abstract

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.

Keywords: Filgotinib; Ozanimod; Tofacitinib; Upadacitinib; inflammatory bowel disease.

Plain language summary

Small Molecules for Patients with IBD of Childbearing Age The maintenance of remission is vital for good fetal and maternal outcomes in IBD pregnancies and biological therapies used in IBD have been associated with favourable pregnancy outcomes. The safety profile of novel small molecules in human pregnancy is however largely unknown. We conducted a RAND appropriateness panel to agree recommendation son the use of Tofacitinib, Filgotinib, Upadacitinib and Ozanimod in women of childbearing age. Tofacitinib, Filgotinib, Upadacitinib and Ozanimod should be avoided during pregnancy due to serious concerns regarding birth defects. Small molecule therapies Tofacitinib, Filgotinib, Upadacitinib and Ozanimod should be given due consideration in the management of IBD in women of childbearing age, provided there are no immediate plans for conception. Counselling about potential risk of adverse effects during pregnancy, risk of venous thromboembolism and effective contraception are needed. Clinicians need to consider time to establish alternative therapies when switching away from Tofacitinib, Filgotinib, Upadacitinib and Ozanimod in the pre-conception period. Future research should examine pregnancy outcomes in cases where Tofacitinib, Filgotinib, Upadacitinib and Ozanimod exposure occurred but data may be difficult to compare to biologics due to differences in exposure duration. Guidelines should be updated as further maternal and fetal safety data become available.

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Conflict of interest statement

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.

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