Background/Purpose: Immune checkpoint inhibitor (ICI) therapy is widely used in the treatment of metastatic melanoma and non-small cell lung cancer and it is under investigation for multiple other cancers (lymphoma, head and neck cancers, renal cell carcinoma, urothelial carcinoma, and breast cancer).  ICIs can cause a variety of immune-related adverse events, including inflammatory arthritis (IA), which is an increasingly recognized complication. A variety of interventions directed at ICI-induced IA, including corticosteroids and biologic DMARDs, have already been published with variable efficacy, but the long term side effects of glucocorticoids and malignancy risk are important challenges in this population.

Methods: We performed a retrospective chart review of all the cases of ICI-induced inflammatory arthritis referred to the Rheumatology service in a single academic center from January 2015 through May 2017 who have had at least one follow-up visit after treatment initiation. We abstracted demographic data, type of ICI used, swollen and tender joint counts, imaging (radiographic and/or high power Doppler ultrasound), laboratory data (C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)), serological data (Rheumatoid Factor (RF), anti-nuclear antibody (ANA) and anti-CCP antibodies), side effects from DMARDs and patterns of rheumatic treatment.

Results: Six patients who had a 2-month follow up were identified: age 63 ± 3.8 years, BMI of 31 ±7.3 kg/m², 5 males and 1 female, all Caucasian with stage IV metastatic melanoma (see Table); four patients developed IA after <5 months of exposure to ICI (7.8 ± 5.6 months); 2 patients developed IA 15 months after initiation of ICI with ulnar styloid erosions seen on radiographs.  All patients received combinations of ipilimumab (Ipi) and/or nivolumab (Nivo) or Pembrolizumab (Pembro) prior to developing IA. At the time of our analysis, 4 patients had stopped ICIs. None of the patients had evidence of other immune/inflammatory disorders. ANA, RF and CCP were negative. Five patients received HCQ (6.5 mg/kg) and SSZ (maximum dose of 2 grams/day), and one received HCQ monotherapy; 4 patients required steroids at maximum dose of 30 mg daily; five patients completely tapered steroids by the second follow up visit; one patient had rash with SSZ. One patient achieved partial remission and 5 patients achieved complete remission of IA within 2 months.

M=male; F=female; S=small; L=large

Conclusion: Combination non-immunosuppressive tDMARDs is a valid alternative in managing ICI-related IA, and it is rapidly effective and well tolerated. Our small series suggests a potential risk for erosive IA in patients managed on corticosteroids alone. Prospective registries are needed to stratify the risk for developing ICI-induced IA and to assess comparative effectiveness among traditional and biologic DMARD regimens.