2028 - Anakinra for the Treatment of Hyper-IgD with Periodic Fever Syndrome in Children

Tuesday, November 8, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
Donald P. Goldsmith1, Karyl S. Barron2, Amanda K. Ombrello3, Robert Lembo3, Deborah Stone3, Anne Jones4, Dawn C. Chapelle Neal5 and Daniel L. Kastner6, 1Drexel University College of Medicine/St Christophers Hosp for Child, Philadelphia, PA, 2NIAID-NIH, Bethesda, MD, 3National Institutes of Health, Bethesda, MD, 4NIH-NIAMS, Bethesda, MD, 5NIAMS, Bethesda, MD, 6National Human Genome Research Institute, National Institutes of Health, Bethesda, MD
Presentation Number: 2028

Background/Purpose:Hyper-IgD with Periodic Fever Syndrome (HIDS) is an autosomal recessive autoinflammatory disorder thought to result from increased inflammasome activation. Various therapeutic agents have been proposed but there is no established treatment. Recent in vitro data indicates increased caspase-1 activity leading to active  IL-I beta release (Kuijk LM et al.Blood 2008;112:3653). In earlier case reports and small series (Rigante d et al. Rheumatol  Int 2006;27:97and van der Hilst JC et al. Medicine 2008; 87:301 ) clinical benefit has been noted using the Il-1 blocker, anakinra. To further explore its efficacy we assessed the therapeutic response of a cohort of pediatric HIDS patients  to anakinra.

Method:This study is a retrospective chart review of 11 children with HIDS. Eleven of 25 patients followed in the NIH Periodic Fever Clinic with known MVK mutations and symptoms compatible with HIDS, ages 4-17, were  treated with anakinra. Five children had only one mutation in the MVK gene. Seven were started on intermittent administration at the onset of a febrile episode and 4 were treated with daily administration. Dosage most often was initiated at 1mg/kg with further increases when needed up to 3-5mg/kg/day. Clinical response was assessed at each outpatient visit by interview and clinical examination with determination of a clinical score based on changes in fever (frequency, duration, and apex), G-I symptoms, arthralgias/arthritis, and rash.

Result:Intermittent Rx (7patients): In 3 children there was a sustained reduction in the severity and frequency of febrile episodes (complete response). In 3 there was a reduction of in the severity but an increased frequency of episodes (partial response). In 1 there was no response (this child later developed JIA associated with dyserythropoietic anemia).

Daily Rx (4 patients): In 1 child there was reduced episode severity and no change in episode frequency (positive response). In 1 child there was reduced severity but increased episode frequency (partial response). In 2 there was no response.

Side effects were confined to localized cutaneous reactions. Those treated with daily therapy were  assessed initially as having more severe clinical manifestations. Of 3 total patients with no clinical response  2 had previously been treated unsuccessfully with etanercept. With this small number of patients we were unable to correlate a specific mutation pattern with therapeutic results.Of note, however was that all 3 children who experienced an increased frequency of episodes had single MVK mutations. 

Conclusion: The majority (8 [72%] ) of 11 children with HIDS demonstrated a beneficial response to anakinra therapy, 4 complete and 4 incomplete.  However, an increased frequency of episodes was an unexpected finding associated with benefit. These data emphasize that predictable, complete and enduring response to treatment  with currently available biologic agents remains elusive. In this regard our results are similar to the analysis of 13 patients (adults and children) with HIDS treated with anakinra as reported by van der Hilst JC et al (Medicine 2008;87:301).


Keywords: anakinra

Disclosure: D. P. Goldsmith, None; K. S. Barron, None; A. K. Ombrello, None; R. Lembo, None; D. Stone, None; A. Jones, None; D. C. Chapelle Neal, None; D. L. Kastner, None.