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Check Point Inhibitors - Something You Gotta Know!

Dr. Janet Pope  Featured
June 15 2017 6:00 AM ET via RheumReports RheumReports

Check point inhibitors are proteins (usually antibodies) used in oncology that upregulate the immune system to attack cancer cells. They upregulate T cells through PD-1 (programmed cell death protein 1) and CTLA-4 (recall that abatacept is a CTLA-4 Ig co-stimulatory molecule inhibitor). Check point inhibitors are used especially in melanoma and some lymphomas, and more indications will likely follow.

Here is why you have to know about them: these drugs will make our patients flare and will also cause new autoimmune problems. 

From my own experience: I have a female patient with SpA (mostly axial) and an occasional knee involved that would be treated only with NSAIDs. She had a melanoma previously. The melanoma returned with a baseball-sized (yes - huge) axillary lymph node where she could not even straighten her arm due to the lymph node. When she was given a check point inhibitor, the lymph node shrunk to the size of a ping pong ball and then virtually resolved over only a few months, but her SpA returned with a vengeance. Her knees have to be regularly drained and injected, and she has new DIP significant synovitis. Her axial spine is OK.

Three check point inhibitors are approved in the US (ipilimumab/Yervoy, pembrolizumab/Keytruda, and nivolumab/Opdivo). Two presentations discussed cases of inflammatory arthritis and other autoimmune conditions due to check point inhibitor therapy for cancer (Calabrese A*, et al OP0003 and Belkhir R, et al OP0004). The first was a series of 19 cases seen at the Cleveland Clinic including 16 that were new autoimmune diseases and 3 that were exacerbations of the patients' pre-existing rheumatology conditions. The diagnoses were inflammatory arthritis, sicca, PMR and myositis, and the majority (seen in the rheumatology clinic) were inflammatory arthritis.

The second series from France reported on 6 patients who all developed seropositive RA after check point inhibitor therapy. In general the RA was treated with NSAIDs and steroids, and less commonly with HCQ, MTX and/or stopping the check point inhibitor. Dr. Belkhir said that in the literature there were 9 previously reported cases with inflammatory arthritis (all seronegative) and 4 with Sjogren’s syndrome. Other reports include thyroid disease and various autoimmune diseases.

*Of human interest, Dr. A Calabrese is a trainee doing rheumatology and infectious diseases combined as a fellowship and is working with…you guessed it, her proud father Dr. L Calabrese, and they are authors together.


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About the Author

Dr. Janet Pope
Dr. Janet Pope

Dr. Janet Pope is Professor of Medicine at Western University and Division Head of Rheumatology. Dr. Pope's research interests include epidemiologic studies in scleroderma, classification criteria in systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis.

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