Issues for surgery
Risk of perioperative flare in disease activity (potentially leading to an increase in glucocorticoid use), if omitted.
Risk of post-operative infection if continued.
Risk of venous thromboembolism (VTE), particularly if continued - see Further information.
Advice in the perioperative period
Elective surgery
Establish indication and dose (see Further information).
The Surgical Team and patient’s Rheumatologist / Gastroenterologist along with the patient should be involved in the planning for elective surgery to balance the potential benefit of preventing post-operative infection by stopping filgotinib against the risk of developing severe or unstable disease.
Modifiable risk factors for perioperative infection, such as glycaemic control and smoking should ideally be addressed prior to surgery.
Glucocorticoid use is associated with increased perioperative infection in a dose dependent manner. Where possible consider delaying elective surgery until patients taking filgotinib can be managed on less than 15mg prednisolone (or equivalent).
Minor procedures
Consider continuing filgotinib before low-risk surgery (i.e. surgery without a break in sterile technique, during which the respiratory, gastrointestinal, and genitourinary tracts are not entered) e.g. endoscopy, bronchoscopy, hysteroscopy, cystoscopy, breast biopsy, dermatologic or ophthalmological procedures.
Ensure adequate thromboprophylaxis if continued (see Further information).
All other procedures
Surgery should be scheduled to enable the patient to miss THREE days of filgotinib (i.e., scheduling surgery for 4 days after last dose of filgotinib).
EXCEPT:
If the Surgical Team deem the procedure to be of especially high infection risk, consider stopping 7 days before surgery. However, a flare in disease activity may occur, which may result in glucocorticoids being administered, further increasing the infection risk.
Emergency surgery
Consider withholding any doses due in the immediate post-operative period to reduce risk of VTE and infection. Monitor closely for infection and postoperative VTE.
Ensure adequate thromboprophylaxis (see Further information).
Perioperative considerations
Control of body temperature and avoidance of blood transfusion may minimise the risk of infection.
Post-operative advice
If stopped, recommence post-operatively once wound healing stable – discuss with Surgical Team. To prevent relapse consideration should be given to restarting filgotinib 3 - 5 days after surgery if no concerns. Ideally treatment interruption should not exceed 14 days (see Further information).
If post-operative bloods indicate haemoglobin, neutrophils or lymphocytes below normal range consult product literature as treatment interruption may be required – discuss with Specialist.
If post-operative VTE, or infection, develops discontinue filgotinib and discuss with Specialist.
Interactions with common anaesthetic agents
None.
Interactions with other common medicines used in the perioperative period
None.
Further information
Indications and dosing frequency
Filgotinib is used for rheumatoid arthritis and ulcerative colitis. This is an oral formulation, and doses are administered once daily.
Venous thromboembolism (VTE) risk
Ensure patients receive adequate thromboprophylaxis when undergoing surgery as serious VTE events have been observed in patients taking filgotinib. In a randomised post authorisation safety study in patients with rheumatoid arthritis who were 50 years of age or older with at least one additional cardiovascular risk factor, a dose-dependent increased risk for VTE was observed with tofacitinib compared to TNF inhibitors. Following a European safety review this increased risk of VTE is regarded as a JAK inhibitor class effect. It is not known if pre-operative cessation of filgotinib reduces the VTE risk back to baseline.
Rationale for recommendations - risk of infection versus risk of disease
Inflammatory arthritis
Filgotinib is known to increase the risk of serious infections, particularly in the elderly, hence use is not recommended in patients over 65 years old unless there is no suitable alternative5. Like other JAK inhibitors filgotinib has a short half-life; approximately 7 hours, and 19 hours for its metabolite. However, concerns that the duration of pharmacodynamic activity of JAK inhibitors is longer than the half-life3 initially led to the American College of Rheumatology / American Association of Hip and Knee Surgeons (ACR / AAHKS) recommending to stop 7 days pre-operatively, however, they have since revised their guidance and recommend stopping other JAK inhibitors 3 days prior to arthroplasty (with the caveat that a longer cessation period may be considered if history of infections or previous prosthetic joint infection). Whilst the ACR / AAHKS guidance does not specifically cover filgotinib it seems reasonable to extrapolate the advice for other JAK inhibitors. This also aligns with the recommendations from the German Society for Rheumatology. The change in advice is attributed to a sub-study which showed a rapid increase in disease activity after discontinuing tofacitinib with patients experiencing flares within 2 weeks, sooner than with TNF inhibitors. These findings are expected to extrapolate to filgotinib.
Ulcerative colitis
Currently there is very limited data on the perioperative safety of JAK inhibitors in patients with IBD; the single study available reported an increase in the number of venous thromboembolic events in patients taking tofacitinib and recommended prolonged use of thromboprophylaxis. Cohen et al recommend stopping JAK inhibitors three days prior to surgery which aligns with the recommendations by rheumatology societies. Their recommendations for restarting JAK inhibitors vary from 3 days to 14 days post-operatively depending on the clinical situation. Figure 2 and 3 in Cohen et al may be useful tools when weighing this decision.
References
Albrecht, K. Poddubnyy, D. Leipe, J. et al. Perioperative management of patients with inflammatory rheumatic diseases: Updated recommendations of the German Society for Rheumatology. Zeitschrift fur Rheumatologie. 2022, 82:1-11 doi:10.1007/s00393-021-01150-9
Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed 31st January 2024]
Cohen, BL. Lincango, E. & Holubar, S. How to manage targeted immune suppressants (biologics and oral small-molecule drugs) perioperatively for inflammatory bowel disease and non-inflammatory bowel disease surgery. Clinical Gastroenterology and Hepatology. 2023; 21:1148-1151 doi: 10.1016/j.cgh.2023.01.042.
Goodman, SM. Springer, BD. Chen AF. American College of Rheumatology and American Association of Hip and Knee Surgeons (AAHKS) 2022 American College of Rheumatology / American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients with Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty. 2022; 74(9):1399-1408 doi:10.1002/acr.24893
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press http://www.medicinescomplete.com [Accessed 31st January 2024]
Kaine, J. Tesser, J. Takiya, L. Re-establishment of efficacy of tofacitinib, an oral JAK inhibitor, after temporary discontinuation in patients with rheumatoid arthritis. Clin Rheumatol. 2020; 39(7):2127-2137 doi:10.1007/s10067-020-04956-1
Moreira P, Correia A, Cerquerira M, Gil M. Perioperative management of disease-modifying antirheumatic drugs and other immunomodulators. ARP Rheumatol. 2022; 3:218-224.
Sebastian, S. Segal, JP. Hedin, C. et al. ECCO Topical Review: Roadmap to Optimal Peri-Operative Care in IBD. Journal of Crohn’s and Colitis. 2023; 17:153-169 doi:10.1093/ecco-jcc/jjac129
Summary of Product Characteristics – Jyseleca (filgotinib) 100 mg film-coated tablets. Galapagos Biotech Limited. Accessed via www.medicines.org.uk 01/02/24 [date of revision of the January 2024]