The clinical course of patients with rheumatoid arthritis who underwent orthopaedic surgeries under disease control by tofacitinib

Tofacitinib (TOF) is the first small-molecule inhibitor of the JAK1 and JAK3 signalling pathways, and has been reported to effectively suppress the synovial inflammation of rheumatoid arthritis (RA) [1,2]. In 2013, the Japanese Ministry of Health, Labour and Welfare approved TOF for the treatment of RA. The EULAR recommendation 2016 update for the management of RA with targeted synthetic and biological disease-modifying anti-rheumatic drugs (tsDMARDS and bDMARDs) included the use of JAK inhibitors as an option for phase II treatment, in the same line of bDMARDs, when phase I treatment has failed due to lack of efficacy and/or toxicity [3]. With the widespread use of TOF among RA patients, the number of patients who require surgical intervention is likely to increase. However, at present, little information is available regarding perioperative discontinuation of TOF. We retrospectively reviewed the cases of nine patients with RA who underwent orthopaedic procedures at Okayama University Hospital and Kurashiki Sweet Hospital. The current study has been approved by the Ethics Committees of our respective institutes. The patients’ characteristics before surgery are summarized in Table 1. Patients comprised seven women and two men, with an average age of 61.4 years (range 33–85), and their average disease duration was 19 years (range 5–30) at the time of surgery. Every patient had experienced at least two primary or secondary failures of bDMARDs before use of TOF. Although the guidelines from the Japan College of Rheumatology (JCR) for post-marketing surveillance of TOF (URL: http://www.ryumachi-jp.com/info/guideline_tofacitinib.html, in Japanese) suggested the use of TOF in patients who showed an inadequate response to more than 8 mg/wk of methotrexate (MTX), six of our patients were unable to tolerate MTX due to side effects and discontinued its use. Five patients used concomitant prednisolone, and no patients had diabetes mellitus as a preoperative complication. Seven patients were receiving treatment with TOF at 10 mg/day and two patients at 5 mg/day. Preoperative average disease activity evaluated by DAS28-CRP was 3.31 (range, 1.33–5.07). The patients underwent a total of 11 procedures, related (n = 7) or unrelated (n = 4) to the RA. Table 2 summarizes the type of surgery, pre- (within 2 days) and post-operative (within 3 days) haemoglobin, serum count of lymphocytes, period needed for wound healing, and postoperative events including surgical site infection (SSI) and delayed wound healing. Because of the short half-life of the TOF and the lack of information, we did not set a pre-operative discontinuation period in all patients. A post-operative decrease in the serum number of lymphocytes to below 1000 cells/µL was seen in five patients with six procedures. Removal of stitches was carried out at an average of 13.8 days post-operatively after confirmation of wound healing. We noted delayed wound healing in one patient who underwent shortening osteotomy of a metatarsal bone for forefoot deformity (Case No. 1), and it healed at postoperative day 25. No instances of SSI were noted in any patient during at least 6 months’ follow-up.