Therapeutic options in IBD-related arthritis for adults

Drug	Dose	Therapeutic notes
Nonsteroidal antiinflammatory drugs (NSAIDs; examples are shown below)
Celecoxib	200 mg orally once daily or 100 mg orally twice daily (maximum 200 mg twice daily)	Useful as a short course (eg, 2 weeks) for inactive IBD and active IBD-related arthritis. Initiate in consultation with the patient's gastroenterologist due to limited evidence that NSAIDs may exacerbate IBD. We suggest a COX-2 selective NSAID (eg, celecoxib, etoricoxib where available). If a nonselective NSAID (eg, naproxen, ibuprofen) is used, administer with a proton pump inhibitor. Not effective for the treatment of uveitis or psoriasis.
Etoricoxib (not available in all countries)	60 to 90 mg orally once daily (maximum 90 mg/day)
Ibuprofen	400 to 800 mg orally 3 to 4 times daily (maximum 2400 mg/day)
Naproxen	250 to 500 mg orally twice daily (maximum 1000 mg/day)
Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs)
Sulfasalazine	500 mg orally twice daily; may increase by 1000 mg/day every 2 weeks until symptoms improve (maximum 1000 mg 3 times daily)	Not effective for the treatment of axial arthritis^*. Data are not available for efficacy of sulfasalazine, azathioprine, or 6-MP in treating enthesitis or dactylitis. Data are limited regarding efficacy of sulfasalazine or 6-MP in treating uveitis. Azathioprine and 6-MP may cause severe hematologic toxicity, particularly in patients with thiopurine S-methyltransferase (TPMT) and/or nudix hydrolase 15 (nucleotide diphosphatase; NUDT15) deficiency. Refer to UpToDate content on these agents for more details on dosing and monitoring.
Methotrexate	Oral^¶ or SUBQ administration: 10 mg once weekly; may increase by 2.5 to 5 mg/week every 1 to 2 weeks until symptoms improve (maximum 25 mg/week) Administer with folic acid 1 mg orally once daily or leucovorin 2.5 to 5 mg orally once weekly approximately 10 to 12 hours after the methotrexate dose
Azathioprine	Please refer to dosing used for IBD
Mercaptopurine (6-MP)	Please refer to dosing used for IBD
Tumor necrosis factor (TNF) inhibitors^Δ
Adalimumab	40 mg SUBQ once every 2 weeks (may escalate to 40 mg weekly or 80 mg every 2 weeks for partial response)^◊
Certolizumab pegol	400 mg SUBQ at weeks 0, 2, and 4, then 200 mg SUBQ once every 2 weeks or 400 mg SUBQ once every 4 weeks	Not approved by the FDA or EMA for treatment of ulcerative colitis, or by the EMA for treatment of Crohn disease.
Golimumab	IV: 2 mg/kg/dose at weeks 0 and 4, then once every 8 weeks (no defined maximum dose) Subcutaneous: 50 mg SUBQ once monthly^◊	Not approved by the FDA or EMA for treatment of Crohn disease.
Infliximab	5 mg/kg/dose IV at weeks 0, 2, and 6, then 5 mg/kg once every 6 to 8 weeks^◊
IL-12/23 inhibitor
Ustekinumab	Administer 45 mg SUBQ at weeks 0 and 4, then every 12 weeks^◊§	May not be as effective for axial arthritis^¥. Not effective for uveitis.
Janus kinase (JAK) inhibitors
Tofacitinib	Extended-release: 11 mg orally once daily^◊ Immediate-release: 5 mg orally twice daily^◊	We generally use 11 mg once daily for improved adherence. Data are not available for efficacy in treating uveitis. Not approved by the FDA or EMA for treatment of Crohn disease.
Upadacitinib	Extended-release: 15 mg orally once daily^◊	Data are not available for efficacy in treating uveitis.

NOTE: Treatment should be performed by clinicians who are experienced in the use, monitoring, adjustment, and drug interactions of these agents because of the potential toxicity of these drugs/combinations and the unpredictability of the disease. Treatment and disease monitoring should be coordinated with the patient's gastroenterologist. Dosing in this table is intended for adults with normal kidney and liver function. For treatment selection, refer to UpToDate content on IBD-related arthritis.

6-MP: mercaptopurine (also known as 6-mercaptopurine); EMA: European Medicines Agency; FDA: US Food and Drug Administration; IBD: inflammatory bowel disease; IL: interleukin; IV: intravenously; SUBQ: subcutaneously.

* Based on data from patients with ankylosing spondylitis.

¶ Divided oral dosing (ie, splitting the weekly dose into 2 or 3 doses spaced evenly, every 12 hours, over a single 24-hour period) or subcutaneous administration is suggested for methotrexate doses >15 mg since oral absorption decreases with higher doses.

Δ We generally do not favor the use of etanercept since it is not effective for IBD.

◊ Patients with active IBD may require higher dosing, as described in the UpToDate content on treatment of IBD.

§ Dosing described is for psoriatic arthritis. Dosing for other indications may be weight-based.

¥ Based on improved Bath Ankylosing Spondylitis Disease Activity Index (BASDAI); no imaging data.

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Therapeutic options in IBD-related arthritis for adults