Checkpoint inhibitor immunotherapy induced inflammatory arthritis secondary to Nivolumab and Ipilimumab: a pediatric first

Our plain-English summary of Checkpoint inhibitor immunotherapy induced inflammatory arthritis secondary to Nivolumab and Ipilimumab: a pediatric first, by J.A. Storwick, H. Tam, D.G. Rosenbaum, et al (Pediatric Rheumatology Online Journal, 2024).

The study

• Authors: J.A. Storwick, H. Tam, D.G. Rosenbaum, K. Houghton
• Journal: Pediatric Rheumatology Online Journal
• Published: 2024;22(1):49
• Type of article: Case report
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Immune checkpoint inhibitors (ICIs) have expanded the arsenal of cancer therapeutics over the last decade but are associated with a spectrum of immune-related adverse events (irAEs), including inflammatory arthritis. While these complications are increasingly recognized in the adult population, no cases of inflammatory arthritis irAEs have been reported in the pediatric literature.

Case Presentation: A 14-year-old female with metastatic epithelioid mesothelioma was referred to the pediatric rheumatology clinic after developing progressive inflammatory joint pain in her bilateral shoulders, hips, and small joints of hands following the second cycle of Nivolumab and Ipilimumab. Initial examinations showed bilateral shoulder joint line tenderness, positive FABERs test bilaterally, tenderness over bilateral greater trochanters, and bilateral second PIP effusions. Her serological profile was notable for positive HLA-B27, positive anti-CCP, negative Rheumatoid Factor, and negative ANA. PET-CT scan performed for disease response following immunotherapy showed symmetric increased metabolic activity primarily involving the supraspinatus, gluteus medius and minimus, and semimembranosus tendon insertions. Her presentation was consistent with a grade 1 irAE that worsened to a grade 2 irAE despite NSAID therapy, prompting a short course of oral prednisolone. She achieved clinical remission of her mesothelioma following six cycles of Nivolumab and Ipilimumab and her inflammatory arthritis was controlled on Celebrex monotherapy.

Conclusions: To our knowledge, this is the first pediatric case of ICI-induced inflammatory arthritis and enthesitis. This case highlights the importance of increasing awareness of diagnosis and management of irAEs in children.

© 2024. The Author(s).

In plain English

This article is a case report about one patient: a girl diagnosed at age 13 with metastatic epithelioid mesothelioma. The article does not discuss asbestos or what caused her cancer. She was treated with two immunotherapy drugs, nivolumab and ipilimumab, and developed joint pain and stiffness after her second treatment cycle. After the third cycle, a PET-CT scan showed a complete response of her mesothelioma. It also showed new increased activity at points where tendons attach to bone in the shoulders, hips, knees and right elbow. Blood tests were positive for HLA-B27 and anti-CCP and negative for rheumatoid factor and ANA. Her arthritis was first graded mild (grade 1) and treated with naproxen. It worsened to grade 2 after the fifth cycle. She then received oral prednisolone, tapered over 3 months without a flare, and celecoxib. At her last follow-up, after six cycles, her mesothelioma was in clinical remission and her arthritis was controlled on celecoxib alone. The authors concluded that, to their knowledge, this was the first report of arthritis linked to these drugs in a child.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Case report of a single patient, with a PubMed literature search for earlier pediatric cases
• Who was studied: One 14-year-old female patient of Caucasian descent, diagnosed at age 13 with metastatic epithelioid mesothelioma. The article first describes pelvic peritoneal nodules and later confirmed chest (thoracic) involvement. She was referred to the authors' pediatric rheumatology clinic. The authors are affiliated with British Columbia Children's Hospital, Vancouver, Canada. No dates are given.
• Exposure: Immune checkpoint inhibitor immunotherapy: 6-weekly cycles of nivolumab on day 1 and ipilimumab on days 1 and 22 of each cycle, given after earlier cisplatin/pemetrexed chemotherapy. The article does not mention asbestos exposure.
• Main results:
  • After her second cycle of nivolumab and ipilimumab, the patient developed joint pain and stiffness in the right elbow, both shoulders, small joints of the hands, knees and hips.
  • After the third cycle, a repeat PET-CT scan showed a complete response of her mesothelioma.
  • The same scan showed new symmetric increased metabolic activity at multiple entheses (tendon attachment points) in the shoulders, hips, knees and right elbow.
  • Blood tests in this patient were positive for HLA-B27 and anti-CCP.
  • Blood tests in this patient were negative for rheumatoid factor and ANA.
  • At first consultation, she was diagnosed with a grade 1 (mild) rheumatic immune-related adverse event.
  • She was treated with naproxen starting at 10 mg/kg/dose twice daily. Her arthritis worsened with each further cycle despite doses increased up to 12 mg/kg/dose twice daily.
  • After the fifth cycle, her symptoms worsened to a grade 2 rheumatic immune-related adverse event, with new limits on her daily activities.
  • She was started on oral prednisolone 0.5 mg/kg/day, and naproxen was changed to celecoxib because of gastrointestinal intolerance. Her pain and function improved significantly, and the steroids were tapered over 3 months without a flare of her arthritis.
  • At her last follow-up, her mesothelioma was in clinical remission after six cycles of nivolumab and ipilimumab.
  • At her last follow-up, her inflammatory arthritis was controlled on celecoxib alone.
  • The authors' PubMed literature search found no published cases of immune checkpoint inhibitor-induced inflammatory arthritis in children.
• The authors' conclusion: The authors concluded that, to their knowledge, this was the first report of inflammatory arthritis associated with nivolumab and ipilimumab therapy in a child. They said the case highlights the need for greater awareness of these rheumatic side effects in children.

Topics

Medical terms in this study, explained in our Lexicon: checkpoint inhibitors, Immunotherapy, Nivolumab (Opdivo), Ipilimumab (Yervoy), Immune-Related Adverse Events, Epithelioid, Mesothelioma, Bilateral.

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