Study Finds Low Rate of Neoplasms in Pediatric Patients Receiving Anti-TNF Therapy

Anti—tumor necrosis factor (anti-TNF) therapy is effective for treating pediatric patients who have rheumatic diseases, but concerns persist about the risk of malignancy associated with these drugs, even though neoplasms are rare in this population. Researchers from The Hospital for Sick Children in Toronto, Ontario, Canada, recently published results of a chart review that assessed pediatric patient data from 357 patients from 1997 to 2013.

These patients, all of whom had rheumatic diseases, were exposed to etanercept, infliximab, adalimumab, golimumab, certolizumab, anakinra, cankinumab, tocilizumab, abatacept, or rituximab, with 21% of the patients having been exposed to more than 1 biologic. The majority of the patients (n = 295) had a diagnosis of juvenile idiopathic arthritis (JIA). The remaining patients had uveitis (n = 23), vasculitis (n = 10), chronic recurrent multifocal osteomyelitis (n = 4), juvenile dermatomyositis (n = 4), systemic lupus erythematosus (n = 4), inflammatory bowel disease-associated arthritis (n = 4), autoinflammatory disease and periodic fever (n = 3), sarcoidosis (n = 3), or another disease (n = 7).

In total, 6 patients were found to have 1 or more neoplasm during or after anti-TNF exposure, resulting in a malignancy rate of 1.68%. The patients who had neoplasms had been exposed to etanercept (n = 1), infliximab (n = 3), or both (n = 2). The median time from anti-TNF initiation to diagnosis with a neoplasm was 5.0 years.

• The patient who had received etanercept developed Ewing sarcoma compressing the brain stem.
• One patient who received infliximab was diagnosed with benign pilomatricoma, the second was diagnosed with diffuse nasopharyngeal carcinoma, and the third was diagnosed with left renal cell carcinoma.
• One patient who had received both etanercept and infliximab developed renal clear cell carcinoma, and the second developed hepatosplenic T-cell lymphoma.

All of these patients had been exposed to methotrexate, and all but 1 received other concomitant medications. It has also been suggested, the authors report, that there may be a background incidence of malignancy in children with inflammatory disease activity, with or without biologic therapy, though studies on this subject have produced conflicting data.

“Most of the neoplasms at our [center] were unusual for the pediatric population,” report the authors. “To the best of our knowledge, this is the first report of benign pilomatricoma and nasopharyngeal carcinoma in a pediatric patient following anti-TNF exposure for rheumatic disease management.”

However, within the JIA subset, “patients had an extremely favorable probability of being neoplasm-free 5 years after initiation of biologics.” Additional long-term studies with larger populations should be completed to identify the types of malignancies that occur in this population, and malignancy screening at each clinical visit is appropriate as part of anti-TNF monitoring of patients receiving biologics.

Reference

Okihiro A, Hasija R, Fung L, et al. Development of neoplasms in pediatric patients with rheumatic disease exposed to anti-tumor necrosis factor therapies: a single Centre retrospective study. Pediatr Rheumatol Online J. 2018;16(1):17. doi: 10.1186/s12969-018-0233-1.