Background CAPS is a rare monogenic autoinflammatory syndrome consisting of a spectrum of three conditions: FCAS, Muckle-Wells syndrome (MWS), and the most severe form, NOMID/CINCA. Progressive hearing loss is a characteristic of severe CAPS¹. Previous analyses showed that long-term Kineret treatment stabilized the progression of hearing loss².

Objectives To evaluate whether long-term Kineret treatment stabilizes hearing loss among pediatric patients, with focus on the subset of infants/toddlers.

Methods A prospective open-label study with long-term extension including 43 patients was conducted at the National Institutes of Health (NIH study 03-AR-0298)^1,2. The patients were classified as children (age < 12 years) or adolescents/adults (age ≥ 12 years) based on age at Kineret treatment start. Focus was put on the subgroup of infants/toddlers (age<2 years at treatment start). Hearing was monitored with audiogram and by presence of lesions in the cochlea for up to 5 years. The audiogram was evaluated with four frequency (0.5/1/2/4 kHz) pure tone average (4F-PTA), based on both air and bone conduction in the ear with best and worst hearing. The longitudinal changes in 4F-PTA were estimated with a mixed model for repeated measures (MMRM).

Results The baseline 4F-PTA correlated with age at treatment start so that older patients presented with more hearing loss. The MMRM analysis of 4F-PTA included 12 children (median follow-up (FU) 60 months) and 9 adolescents/adults (median FU 54 months). The mean (SD) baseline 4F-PTA in the best ear based on air conduction was 27.6 (19.6) dB HL in children and 53.5 (32.2) dB HL in adolescents/adults. No significant changes were seen in mean 4F-PTA at any time point up to 5 years in either children or adolescents/adults; thus, hearing remained stable. The estimated change from baseline to 5 years was -1.0 dB HL (95% CI -8.6 to 6.6) in children and 2.7 dB HL (95% CI -2.1 to 7.5) in adolescents/adults. Comparable findings were seen in the worst ear and for both ears based on bone conduction assessments. In the subset of 5 infants/toddlers (median FU 48 months), the audiogram monitoring was started after 1-3 years of treatment. The hearing in the best ear remained normal (4F-PTA ≤20 dB HL) in all infants/toddlers at all visits except one transient elevation to 21 dB HL. One of the 5 infants/toddlers presented with a moderate conductive hearing loss (4F-PTA 65 dB HL) in the worst ear associated with middle ear effusion. The audiogram results were supported by non-increased proportion of cochlear enhancement.

Conclusions Correlation between the audiogram and age at treatment start is consistent with progressive hearing loss observed in untreated NOMID patients. Kineret treatment for up to 5 years stabilized the progression of hearing loss in both pediatric and adolescent/adult patients as well as in infants/toddlers. Efforts should be made for early diagnosis of the disease and early treatment initiation.

References

1. Goldbach-Mansky et al. N Engl J Med 2006;355:581–92.

2. Sibley et al. Arthritis Rheum 2012;2375–86

References

Disclosure of Interest M. Leinonen Consultant for: Swedish Orphan Biovitrum AB, K. Söderberg Employee of: Swedish Orphan Biovitrum AB, H. Olivecrona Employee of: Swedish Orphan Biovitrum AB, M. Aldén Raboisson Employee of: Swedish Orphan Biovitrum AB, C. Sibley: None Declared, C. Brewer: None Declared, N. Plass: None Declared, K. King: None Declared, C. Zalewski: None Declared, J. Kim: None Declared, D. Stone: None Declared, D. Chapelle: None Declared, R. Goldbach-Mansky Grant/research support from: Swedish Orphan Biovitrum AB, Regeneron, and Novartis