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 / Dermatologist 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 baricitinib 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 baricitinib can be managed on less than 15mg prednisolone (or equivalent).
Minor procedures
Consider continuing baricitinib 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 baricitinib (i.e., scheduling surgery for 4 days after last dose of baricitinib).
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.
Patients with coronavirus (COVID-19)
If elective surgery is scheduled in a patient recently treated with baricitinib for COVID-19 shared decision making should consider the risks of proceeding with surgery, in relation to baricitinib use and the potential for increased complications due to recent COVID-19 infection.
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 post-operative VTE.
Ensure adequate thromboprophylaxis (see Further information).
Patients presenting with new onset abdominal signs and symptoms
Patients presenting with new onset abdominal signs and symptoms should be evaluated promptly for early identification of diverticulitis or gastrointestinal perforation. If diagnosed stop baricitinib and discuss with Specialist – see Further information.
Patients with coronavirus (COVID-19)
If urgent surgery is required in a patient being treated with baricitinib for COVID-19 shared decision making should consider the risks of proceeding with surgery, in relation to baricitinib use and the potential for increased complications due to concomitant COVID-19 infection.
Perioperative considerations
Control of body temperature and avoidance of blood transfusion may minimise the risk of infection1.
Post-operative advice
Recommence post-operatively once wound healing stable – discuss with Surgical Team. To prevent relapse consideration should be given to restarting baricitinib 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 or liver function tests elevated, consult product literature as treatment interruption may be required – discuss with Specialist.
If post-operative VTE, or infection, develops discontinue baricitinib and discuss with Specialist.
Interactions with common anaesthetic agents
None.
Interactions with other common medicines used in the perioperative period
None.
Further information
Indications, dosing frequency and half-life
Baricitinib is used for rheumatoid arthritis, atopic eczema, and alopecia areata. 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 baricitinib. 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 tumour necrosis factor (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 baricitinib reduces the VTE risk back to baseline.
MHRA / CHM advice: Baricitinib (Olumiant): increased risk of diverticulitis, particularly in patients with risk factors (August 2020)
A European review of worldwide data concluded baricitinib is associated with an increased risk of diverticulitis. The MHRA recommend baricitinib is used with caution in patients with pre-existing diverticular disease, or who are taking non-steroidal anti-inflammatory drugs, corticosteroids, or opioids due to the risk for gastrointestinal perforation. Patients should be advised to seek immediate medical attention if they experience severe abdominal pain especially accompanied with fever, nausea or vomiting, or other symptoms of diverticulitis.
Rationale for recommendations - risk of infection versus risk of disease
Inflammatory arthritis
Baricitinib 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 alternative. Baricitinib has a short half-life; approximately 12 hours. However, concerns that the duration of pharmacodynamic activity of JAK inhibitors is longer than the half-life 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 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). This 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 baricitinib.
Eczema
Whilst there are currently no recommendations from dermatology societies regarding the perioperative management of JAK inhibitors it seems reasonable to extrapolate the recommendations from rheumatology societies.
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
Baricitinib. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. Electronic version. Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com [Accessed 24th May 2024]
Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed 31st January 2024]
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.
Summary of Product Characteristics – Olumiant (baricitinib) 2 mg Film-Coated Tablets. Eli Lilly and Company Limited. Accessed via www.medicines.org.uk 31/01/24 [date of revision of the text September 2023]