Patients in the baricitinib phase 3 clinical trials were excluded if they

• had any major surgery within 8 weeks prior to study entry, or
• would require major surgery during the study, that in the opinion of the investigator in consultation with Eli Lilly and Company or its designee would pose an unacceptable risk to the patient.5

There were no pre-defined criteria for perisurgical administration of baricitinib in the 4 phase 3 clinical trial protocols.5

Administration of baricitinib for patients who required surgery while enrolled in the clinical trials was left to the judgment of the investigator.5

The All BARI RA analysis set included 3770 patients with RA who received baricitinib at a variety of doses from 1 phase 1, 3 phase 2, and 5 phase 3 studies (RA-BEGIN, RA-BEAM, RA-BUILD, RA-BEACON, and RA-BALANCE). Data includes a long-term extension study (RA-BEYOND) with

• 14,744 patient years exposure (PYE) to baricitinib
• 15,114 patient years overall observation including time on baricitinib and follow-up
• median exposure of 4.6 years, and
• maximum exposure of 9.3 years.6

Within the All BARI RA dataset, 122 (3.2%) patients had a temporary interruption of baricitinib due to a medical or surgical procedure.5

A set of guidelines, specifically for patients with rheumatic diseases undergoing elective total hip arthroplasty (THA) or total knee arthroplasty (TKA), was published by the American College of Rheumatology (ACR) and American Association of Hip and Knee Surgeons (AAHKS).9

The 2017 ACR/AAHKS guidelines covered a broad range of antirheumatic drug therapies including DMARDs glucocorticoids, and the JAK inhibitor, tofacitinib.9

Assessment of cardiac risk factors and perioperative venous thromboembolism prophylaxis were not addressed in the 2017 ACR/AAHKS guideline9; however, the expert panel referenced existing published guidelines on these topics.12,13

A full updated guideline from the ACR/AAHKS is expected summer of 2022, but a summary of updates of this guideline is published. Recommendations include patients continue DMARDs through surgery, and to withhold biologics prior to and through surgery.

It is recommended that JAK inhibitors, including baricitinib, be withheld 3 days prior surgery and may be restarted in RA patients once

• the wound shows evidence of healing
• any sutures/staples are out
• there is no significant swelling, erythema or draining, and
• there is no ongoing non-surgical site infection (typically about 14 days).10

Of note, this recommendation is based on infection risk and does not account for the risk of cardiac events or venous thromboembolism.10

The Canadian Rheumatology Association and the British Society for Rheumatology have published recommendations for withholding biologic DMARDs in the perioperative setting based on

• type of surgery
• patient factors, and
• pharmacokinetic parameters of the medications.4,7,14

Both associations recommend re-starting biologic DMARD therapy upon satisfactory wound healing.4,7,14

Updated guidelines published by the British Society for Rheumatology in 2018 provide recommendations for the timing of surgery based on drug dosing intervals and pharmacokinetic half-lives of various biologic therapies.14

Both associations also provided guidance for perioperative management of the conventional DMARDs, including methotrexate, but do not list specific recommendations for JAK inhibitors.4,8

The German Society of Rheumatology (DGRh) publishes monitoring sheets for antirheumatic therapies. These monitoring sheets summarize clinical information including

• recommended dose
• onset of action
• laboratory monitoring
• contraindications
• adverse events, and
• drug-drug interactions.15

Regarding perioperative management, the January 2021 edition of the DGRh monitoring sheet for baricitinib discussed that

• there are not yet sufficient data regarding the risk of infection and wound healing during surgical procedures with baricitinib, and
• considering the half-life, a break of baricitinib is recommended for several days prior to major surgery.15

The DGRh also has a guideline on the perioperative management of patients with rheumatic diseases. The 2021 update recommends that JAK inhibitors should be paused for 3 to 4 days prior to surgery, and start therapy as soon as possible depending on wound healing.11