Faculty Bibliography

Febrile infection-related epilepsy syndrome (FIRES) is a devastating epileptic encephalopathy with limited treatment options and an unclear etiology. Anakinra is a recombinant version of the human interleukin-1 receptor antagonist used to treat autoinflammatory disorders. This is the first report of anakinra for treatment of a child with super-refractory status epilepticus secondary to FIRES. Anakinra was well tolerated and effective. Cerebral spinal fluid analysis revealed elevated levels of proinflammatory cytokines before treatment that normalized on anakinra, suggesting a potential pathogenic role for neuroinflammation in FIRES. Further studies are required to assess anakinra efficacy and dosing, and to further delineate disease etiology. Ann Neurol 2016;80:939-945.

OBJECTIVE: Studies suggest that circulating type I interferon (IFN) may predict response to biological agents in rheumatoid arthritis (RA). Prediction of response prior to initiating therapy would represent a major advancement. METHODS: We studied sera from a test set of 32 patients with RA from the Auto-immune Biomarkers Collaborative Network Consortium and a validation set of 92 patients with RA from the Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository registry. The test set included those with good response or no response to tumour necrosis factor (TNF) inhibitors at 14 weeks by European League Against Rheumatism criteria. The validation set included subjects with good, moderate or no response at 12 weeks. Total serum type I IFN activity, IFN-alpha and IFN-beta activity were measured using a functional reporter cell assay. RESULTS: In the test set, an increased ratio of IFN-beta to IFN-alpha (IFN-beta/alpha activity ratio) in pretreatment serum associated with lack of response to TNF inhibition (p=0.013). Anti-cyclic citrullinated peptide antibody titre and class of TNF inhibitor did not influence this relationship. A receiver-operator curve supported a ratio of 1.3 as the optimal cut-off. In the validation set, subjects with an IFN-beta/alpha activity ratio >1.3 were significantly more likely to have non-response than good response (OR=6.67, p=0.018). The test had 77% specificity and 45% sensitivity for prediction of non-response compared with moderate or good response. Meta-analysis of test and validation sets confirmed strong predictive capacity of IFN-beta/alpha activity ratio (p=0.005). CONCLUSIONS: Increased pretreatment serum IFN-beta/alpha ratio strongly associated with non-response to TNF inhibition. This study supports further investigation of serum type I IFN in predicting outcome of TNF inhibition in RA.

A population-based cohort was utilized to evaluate medications and intra-articular injection utilization for patients with juvenile idiopathic arthritis (JIA) to inform clinical practice and further research. In a geographically defined population, all incident cases of JIA cases were identified between January 1, 1994 and December 31, 2013 based first on diagnosis code followed by medical chart confirmation. Medications and intra-articular glucocorticoid injections were abstracted. Predictors of the first disease-modifying antirheumatic drug (DMARD)/biologic and injections were reported as a hazard ratio (HR) with 95 % confidence intervals (CIs) adjusted for age and sex. Kaplan-Meier methods evaluated therapy at 6 months and 1 year. Injections were reported per 100 person-years (py) with 95 % CI using the Poisson methods. Seventy-one incident cases were identified. Forty-two (59 %) were female with mean age (standard deviation) at diagnosis of 8.2 (5.3) years. Twenty-six (37 %) utilized at least one DMARD or biologic, in which 77 % of these were prescribed in the first 6 months. Subtype of JIA was significantly associated with DMARDs/biologics (p < 0.001). Intra-articular injections were performed in 48 %. The rate of intra-articular injections was 20.7 per 100 py (95 % CI 16.5, 25.6). The rate of joint injections was higher in the first year after diagnosis (p < 0.001) and more common in recent years (p < 0.001). The majority of patients with JIA in a modern population-based cohort do not require DMARDs or biologics. In those who do, the majority receives these within the first 6 months. Intra-articular injections were utilized in almost half of patients with JIA and were increasingly used.

OBJECTIVE: To evaluate the incidence and prevalence of juvenile idiopathic arthritis (JIA) in Olmsted County, Minnesota in 1994-2013 and trends in juvenile rheumatoid arthritis (JRA) in 1960-2013. METHODS: Cases of arthritis in 1994-2013 were identified by diagnosis code with medical chart review to confirm diagnosis separately for JIA and JRA. Overall incidence rates with 95% confidence intervals (95% CIs) were age and sex adjusted to the 2010 US white population. Comparisons were made with an earlier (1960-1993) cohort from this same population. RESULTS: Seventy-one incident cases of JIA in 1994-2013 were identified, with an overall age- and sex-adjusted incidence rate of 10.3 per 100,000 (95% CI 7.9-12.7). Forty-two (59%) were female, with an incidence of 12.4 per 100,000 (95% CI 8.6-16.2), as compared to 8.3 per 100,000 (95% CI 5.2-11.3) in males. The most common subtype was oligoarthritis (63%). The mean +/- SD age at diagnosis was 8.2 +/- 5.3 years. The prevalence of JIA on January 1, 2000 and January 1, 2010 was 51.0 per 100,000 (95% CI 25.2-76.8) and 57.6 per 100,000 (95% CI 31.0-94.5), respectively. When the annual incidence of JRA was compared over time from 1960 to 2013, there was no significant change in incidence overall; however, the incidence decreased among females (P = 0.003). A cyclic pattern of incidence was observed, with peaks approximately every 10 years. Similar to the findings with regard to incidence, prevalence did not change overall, but decreased among females (P = 0.048). There were 4 deaths in the cohort of JRA patients diagnosed in 1960-2013; the standardized mortality ratio was 1.50 (95% CI 0.41-3.83). CONCLUSION: Incidence of juvenile arthritis overall in Olmsted County, Minnesota has not changed significantly in the past 53 years. A consistent cyclic pattern was noted.