ARTHRITIS INDUCED BY IMMUNOTHERAPY

Inflammatory arthritis is a newly recognized toxicity associated with immune checkpoint blockade, and now, for the first time, there is an algorithm to help clinicians recognize and manage it.

"Immune checkpoint inhibitor-induced inflammatory arthritis is an underappreciated immune-related adverse event that may be clinically severe, rapidly destructive, disabling, and affect a patient's quality of life," lead author of the algorithm, Jarushka Naidoo, MD, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, told Medscape Medical News.

Dr Naidoo provided some background. 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 (Ann Rheum Dis. 2016;76:43-50).

"From there, it became obvious to us that this was a newly recognized toxicity of this newly approved group of agents and that clinicians would need to become familiar with how to recognize and diagnose this condition," she said.

Accordingly, Dr. Naidoo and her team created an algorithm, which was published online June 2  in The Oncologist.

The tool separates toxicity according to grade, as defined by the Common Toxicity Criteria for Adverse Events, and suggests the appropriate investigations (rheumatologic examination, laboratory tests, and imaging) and management strategies. The latter includes nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids for milder grades and methotrexate and tumor necrosis factor inhibition for more severe symptoms.

Symptoms are categorized by severity into grades 1, 2, and 3.

"In general, we are looking for joint pain; inflammatory symptoms, which can be defined as joint stiffness after sleep or inactivity or an improvement in symptoms with movement or heat; and joint swelling, which is evident on a clinical exam," Dr. Naidoo explained.

If the symptoms affect the patient's activities of daily living, then several investigations or tests are suggested. These include blood tests for antinuclear antibody, rheumatoid factor, anticyclic citrullinated peptide, and human leukocyte antigen B27.

Recommended supportive treatments include NSAIDs, topical steroids, or intra-articular steroids. If the toxicity is more 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.

Follow-up frequency depends on the severity of symptom toxicity.

"If they have been started on steroids, they need to be monitored every few weeks, and the steroid dose reduced over time. Also any side effects from other medications need to be monitored for, as well," said Dr Naidoo.

"In some cases, treatment with immune checkpoint blockade will have to be discontinued, if symptoms do not improve in 4 to 6 weeks," she said.

While inflammatory arthritis may appear to be a rare toxicity, it may be seen increasingly in the future, Dr. Naidoo said.

The number of cases is expected to grow as the number of patients receiving cancer immunotherapies increases.

The Johns Hopkins algorithm is the first for this toxicity. However, national groups, such as the National Comprehensive Cancer Network and American Society of Clinical Oncology, are developing similar guidelines. "I would anticipate that there will be more algorithms like this and data published to support approaches in the future," she said.

A Timely Paper

"The paper is timely," Rizwan Haq, MD, PhD, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, told Medscape Medical News.

"We have rushed to use these sorts of treatments, and the legacy has been that while we are treating more patients effectively, we also affect their quality of life through things like the arthritis described in this manuscript," Dr Haq said.

It is essential to inform patients about such side effects, he added.

Dana Farber research indicates that about 10% to 15% of patients treated with immune checkpoint blockade have inflammatory arthritis.

The symptoms may not always be manageable, Dr Haq said. "This paper demonstrates that some of these symptoms are quite difficult to treat and might preclude patients who develop these symptoms from continuing on their treatment with immune checkpoint blockade."

Dr Naidoo has received research funding from Merck and AstraZeneca MedImmune; has served as a consultant or on advisory boards for Astra Zeneca MedImmune and Bristol-Myers Squibb; and has received honoraria from Bristol-Myers Squibb and Astra Zeneca MedImmune. Dr. Haq has disclosed no relevant financial relationships.

Oncologist  Published online May 26, 2017. Full text