Use of Tofacitinib for the Treatment of Arthritis Associated With Vedolizumab in Ulcerative Colitis

Introduction: Tofacitinib is a Janus kinase 1-3 inhibitor currently approved for treatment of rheumatoid arthritis, but has demonstrated efficacy for moderate to severe ulcerative colitis (UC) in phase 3 trials. We present a case of a patient with both UC and inflammatory arthritis.Figure: Index finger and 5th digit synovitis while on vedolizumab and before tofacitinib treatment.Figure: Resolution of joint swelling 8 weeks after tofacitinib treatment.Case: A 40 year old non-smoking woman with a history of ulcerative colitis (UC) presented for a second opinion regarding management of medically resistant disease. She was diagnosed with proctitis 8 years prior while pregnant. At that time, she was managed with 5-ASA orally and topically with some improvement, but during her second pregnancy her colitis relapsed and was found to have extended to involve the left colon. She was subsequently treated with steroids, 6-MP and infliximab with some improvement in her disease control. She had some intermittent hand and ankle joint pain when her colitis was active, which was controlled with steroids and then with infliximab. After 18 months, she lost response to infliximab and was found to have developed anti-drug antibodies. She was cycled to certolizumab without response and then evaluated here. Vedolizumab was started at usual loading and maintenance dosing of 300 mg IV q8 weeks with rapid clinical remission. However, her prior joint pains now presented with synovitis of her right index finger and right fifth digit DIP and PIP joints (image 1). Methotrexate was initiated, first at doses of 10 mg PO weekly, and then increased to doses of 20 mg SC weekly. There was some improvement in the arthritis, but not complete resolution, with ongoing exacerbations during menses and other times. Rheumatologic evaluation was negative for rheumatoid factor or other systemic immune markers except ANA >1:1280. Because of persistent joint inflammation, methotrexate was discontinued and tofacitinib 5 mg PO BID was started, followed by extended release formulation of 11 mg PO QD. Vedolizumab was continued for approximately 3 months and then discontinued. In 3 months subsequent follow-up, she remains in clinical remission from her colitis and without any joint problems (image 2). Discussion: This patient had a history of UC and a predominant extra-intestinal manifestation of arthritis. Although her UC was well managed with vedolizumab, her arthralgias progressed to frank asymmetric synovitis. Although her joint problems may represent an independent process, it is also possible that the gut selectivity of vedolizumab may have “uncovered” and exacerbated an underlying seronegative arthritis. Tofacitinib offers a non-selective anti-inflammatory treatment that in this case successfully maintained her colitis while also controlling her arthritis/synovitis. To our knowledge this is the first patient treated for both UC and arthritis with tofacitinib, the first patient treated with concomitant tofacitinib and vedolizumab, and the first patient with UC to receive the extended release formulation of tofacitinib. This case provides insight into future management options in UC and such extra-intestinal manifestations.