Managing Inflammatory Arthritis From Checkpoint Inhibitors

Inflammatory arthritis is a newly recognized side effect associated with immune checkpoint blockade, an increasingly used treatment for a number of cancers.

According to Johns Hopkins doctors who submitted the report, immune checkpoint inhibitor-induced inflammatory arthritis is underappreciated and may be clinically severe, rapidly destructive, disabling, and affect a patient’s quality of life.

Immune Checkpoint Inhibitors

Immune checkpoint inhibitor drugs are currently the most widely used and publicized precision immunotherapy treatment. A patient’s cancer cells can express molecules that activate PD-1 or CTLA-4 inhibitory “receptors” on their “T-cells” or other cells in the immune system.  When these receptors are activated on the T-cells, they are prevented from attacking the cancer cells and evade the immune response.  Checkpoint inhibitor drugs that block PD-1, PD-L1, or CTLA-4 work to “release the brakes” allowing the cancer cells to be detected and attacked by T-cells.

Reports of checkpoint inhibitor – induced inflammatory arthritis have begun appearing in the medical literature. Last year, Johns Hopkins rheumatologists reported a series of 13 patients who had developed rheumatologic complications while being treated with immune checkpoint blockade, of whom 9 had developed inflammatory arthritis.1   According to Johns Hopkins doctors who submitted the report, immune checkpoint inhibitor-induced inflammatory arthritis is underappreciated and may be clinically severe, rapidly destructive, disabling, and affect a patient’s quality of life. It may impact as many as 10% to 15% of patients being treated with a checkpoint inhibitor.

The Hopkins physicians have defined a treatment approach to help practicing clinicians recognize and treat this condition.2

Joint pain and other inflammatory symptoms, such as joint stiffness after sleep or inactivity or an improvement in symptoms with movement or heat; and joint swelling appear to be the hallmarks of the condition and are categorized by severity into grades 1, 2, and 3.  If the symptoms are severe enough to affect the patient’s activities of daily living, then additional tests may be warranted. These include blood tests for antinuclear antibody, rheumatoid factor, anticyclic citrullinated peptide, and human leukocyte antigen B27.

The doctors suggest similar management strategies to those used in the treatment of rheumatoid arthritis; non-steroidal anti-inflammatory drugs (NSAIDs) and steroids for mild cases and methotrexate and tumor necrosis factor inhibition for more severe symptoms.  If the inflammation is severe, then a higher dose of steroid in oral form is suggested. In some cases, added immunosuppression may be used, in consultation with a rheumatologist, and in some situations, treatment with immune checkpoint blockade will have to be discontinued, if symptoms do not improve in 4 to 6 weeks.

Importantly for cancer patients being treated with checkpoint inhibitors, they need to bring any symptoms of joint pain or stiffness to the attention of their treating physician. 

References

  1. Ann Rheum Dis.2016;76:43-50 
  2. http://theoncologist.alphamedpress.org/content/22/6/627.short?rss=1

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