The biologic drug anakinra appears to be effective in treating children with secondary hemophagocytic lymphohistiocytosis (sHLH)/macrophage activation syndrome (MAS), a dangerous “cytokine storm” that can emerge from infections, cancer, and rheumatic diseases.
Children with systematic juvenile idiopathic arthritis (sJIA) and sHLH/MAS are especially good candidates for treatment with the interleukin-1 receptor antagonist anakinra (Kineret), in whom its safety and benefits have been more widely explored than in pediatric patients with sHLH/MAS related to non-sJIA underlying conditions.
In a study published in Arthritis & Rheumatology, Esraa Eloseily, MD, and colleagues at the University of Alabama at Birmingham, looked at hospitalization records for 44 children (mean age, 10 years; n = 25 females) with sHLH/MAS. The children in the study had heterogeneous underlying conditions including leukemias, infections, and rheumatic diseases. About one-third of patients had no known rheumatic or autoimmune disorder.
Dr. Eloseily and colleagues found that early initiation of anakinra (within 5 days of hospitalization) was significantly associated with improved survival across the cohort, for which mortality was 27%. Thrombocytopenia (less than 100,000/mcL) and STXBP2 mutations were both seen significantly associated with mortality.
Patients with blood cancers – even those in remission at the time of treatment – did poorly. None of the three patients in the cohort with leukemia survived.
Importantly, no deaths were seen among the 13 patients with underlying SJIA who were treated with anakinra, suggesting particular benefit for this patient group.
“In addition to the 10% risk of developing overt MAS as part of sJIA, another 30%-40% of sJIA patients may have occult or subclinical MAS during a disease flare that can eventually lead to overt MAS,” Dr. Eloseily and colleagues wrote. “This association of MAS with sJIA suggested that anakinra would also be a valuable treatment for sJIA-MAS.”
The investigators acknowledged that their study was limited by its retrospective design and “nonuniform approach to therapy, lack of treatment controls, and variable follow-up period.” The authors also acknowledged the potential for selection bias favoring anakinra use in patients who are less severely ill.
In a comment accompanying Dr. Eloseily and colleagues’ study, Sarah Nikiforow, MD, PhD, of the Dana-Farber Cancer Institute in Boston, and Nancy Berliner, MD, of Brigham & Women’s Hospital in Boston, urged clinicians not to interpret the study results as supporting anakinra as “a carte blanche approach to hyperinflammatory syndromes.”
While the study supported the use of anakinra in sJIA with MAS or sHLH, “we posit that patients [with sHLH/MAS] in sepsis, cytokine release syndrome following chimeric antigen receptor T-cell therapy, and other hyperinflammatory syndromes still require individualized approaches to therapy,” Dr. Nikiforow and Dr. Berliner wrote, adding that, “in several studies and anecdotally in our institutional practice, cytotoxic chemotherapy was/is preferred over biologic agents in patients with evidence of more severe inflammatory activity.”
Outside sJIA, Dr. Nikiforow and Dr. Berliner wrote, “early anakinra therapy should be extended to treatment of other forms of sHLH with extreme caution. Specifically, the authors’ suggestion that cytotoxic therapy should be ‘considered’ only after anakinra therapy may be dangerous for some patients.”
Two of Dr. Eloseily’s coinvestigators reported financial and research support from Sobi, the manufacturer of anakinra. No other conflicts of interest were reported.
SOURCES: Eloseily E et al. Arthritis Rheumatol. 2019 Sep 12. doi: 10.1002/art.41103; Nikiforow S, Berliner N. Arthritis Rheumatol. 2019 Sep 16. doi: 10.1002/art.41106.