By Ramana S. (Bob) Moorthy, MD
This study found that while disease-modifying anti-rheumatic drugs (DMARDs) and biologics are effective for managing pediatric patients with rheumatic diseases, patients with refractory disease requiring ongoing drug therapies should have malignancy/neoplasm surveillance as part of routine clinical care.
Two things that I took away from this mini-paper were that solid tumors or visceral tumors can occur with biologics and that continued long-term surveillance for secondary neoplasia must be a part of routine clinical care of patients on DMARDs and especially alkylating agents and biologics.
The authors reviewed the charts of 357 children with childhood rheumatologic diseases, 302 of which had juvenile idiopathic arthritis. Six of the 357 (1.68%) developed neoplasia: four with juvenile idiopathic arthritis, one with idiopathic uveitis and one with polyarteritis nodosa.
Interestingly, in the subgroup that developed neoplasms, the median age of rheumatologic disease onset was 3.4 years, and neoplasm was diagnosed at a median age of 10.1 years. Five of the six cancers were malignant.
The six patients with neoplasia were exposed to an average of three DMARDs over their rheumatologic course, with methotrexate being the most common (5/6 patients). Surprisingly, the time from DMARD initiation to diagnosis of neoplasm was shorter (5.4 years) for methotrexate alone compared to all DMARDs (10.1 years).
All patients diagnosed with neoplasia were treated with DMARDs and biologics. Two were on infliximab alone, two on etanercept alone and two on multiple biologics (both etanercept and infliximab).
The median time between initiation of biologics to diagnosis of neoplasia was five years. However, two patients also received cyclophosphamide and etopiside, both of which have been linked to secondary neoplasia. One of these patients developed two malignancies (tonsillary lymphoproliferative disorder and renal carcinoma) five years apart and one developed hepatosplenic lymphoma.
There are many confounding factors in the patients who developed secondary neoplasia, including the use of alkylators and referral patterns which may have led to the inclusion of those with the most serious inflammatory diseases.