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. 2017 Jan;76(1):43-50.
doi: 10.1136/annrheumdis-2016-209595. Epub 2016 Jun 15.

Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab

Laura C Cappelli  1 , Anna Kristina Gutierrez  1 , Alan N Baer  1 , Jemima Albayda  1 , Rebecca L Manno  1 , Uzma Haque  1 , Evan J Lipson  2 , Karen B Bleich  3 , Ami A Shah  1 , Jarushka Naidoo  2 , Julie R Brahmer  2 , Dung Le  2 , Clifton O Bingham 3rd  1
Affiliations

Inflammatory arthritis and sicca syndrome induced by nivolumab and ipilimumab

Laura C Cappelli et al. Ann Rheum Dis. 2017 Jan.

Abstract

Objectives: Immune checkpoint inhibitors (ICIs) targeting the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) pathways have demonstrated survival improvements in multiple advanced cancers, but also cause immune-related adverse events (IRAEs). IRAEs with clinical features similar to rheumatic diseases have not been well described. We report patients with inflammatory arthritis and sicca syndrome secondary to ICIs.

Methods: We report patients evaluated in the Johns Hopkins Rheumatology clinics from 2012 to 2016 identified as having new rheumatological symptoms in the context of treatment with ipilimumab (anti-CTLA-4) and/or nivolumab (anti-PD-1) for solid tumours.

Results: We identified 13 patients who received ICIs and developed rheumatological IRAEs. Mean age was 58.7 years. Cancer types included melanoma, non-small cell lung cancer, small cell lung cancer and renal cell carcinoma. ICI regimens included nivolumab or ipilimumab as monotherapy (n=5), or combination nivolumab and ipilimumab (n=8). Nine of 13 patients developed an inflammatory arthritis, 4 with synovitis confirmed on imaging (3 ultrasound, 1 MRI) and 4 with inflammatory synovial fluid. Four patients developed sicca syndrome with severe salivary hypofunction. Other IRAEs included: pneumonitis, colitis, interstitial nephritis and thyroiditis. Antinuclear antibodies were positive in 5 out of 13 patients. All 13 patients were treated with corticosteroids with varying response. Two patients were treated with methotrexate and antitumor necrosis factor therapy for inflammatory arthritis.

Conclusions: As ICIs are increasingly used for a range of malignancies, new cases of rheumatic IRAEs are likely to emerge. Further research is required to understand mechanisms, determine risk factors and develop management algorithms for rheumatic IRAEs.

Keywords: Arthritis; Autoimmune Diseases; Inflammation; Sjøgren's Syndrome.

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Figures

Figure 1
Figure 1
Ultrasound imaging of talonavicular joint showing erosions and synovitis. (A) Grey-scale ultrasound showing a hypoechoic focus (arrow) and erosions (arrowhead). (B) Power Doppler ultrasound showing enhancement of synovitis.
Figure 2
Figure 2
MRI of left ankle. T2 fat-suppressed image showing tibiotalar synovitis.
See this image and copyright information in PMC

Comment in

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