Background/Purpose

Cryopyrin-Associated Periodic Syndromes (CAPS) include a group of rare inherited autoinflammatory diseases consisting of FCAS, Muckle-Wells Syndrome and the most severe form, NOMID. Reduction in the use of steroids as concomitant medication is a treatment goal for anakinra-treated CAPS patients, since inappropriate use of steroids could lead to increased toxicity. Adverse events (AEs) related to the cardiovascular system are along with infections most frequently reported in steroid-treated patients with rheumatic diseases (Hoes et al Ann Rheum Dis. 2007;66,1560-67). Among 16 patients with severe CAPS treated with anakinra and taking steroids at baseline, the mean daily prednisone-equivalent dosage has been reported to decrease from 0.80 mg/kg/day at baseline to 0.033 mg/kg/day after 60 months (Sibley et al. Arthritis Rheum. 2012;64:2375-86). The objective of the present analysis is to further evaluate the steroid-sparing potential and its consequences in an expanded cohort of patients with severe CAPS treated with anakinra.

Methods

A prospective, open-label withdrawal design study of anakinra treatment with long-term extension including 43 patients was conducted at the National Institutes of Health (Goldbach-Mansky et al. NEJM. 2006;355:581-92). The primary efficacy endpoint, Diary Symptom Sum Score (DSSS), collected daily up to 60 months, included 5 symptoms (fever, rash, joint pain, vomiting, headache); each scored from 0 (no symptoms) to 4 (severe symptoms). Use of steroid medication was obtained from the patient diary. The prednisone dose was to be decreased by 20% at each study visit in which the subject’s disease activity was “moderately” or “significantly” improved. Different types of steroids were converted into prednisone-equivalent doses to enable comparisons. The AEs were analyzed with the infection rate (number of infections per patient years of treatment).

Results

During the study, the proportion of patients in the ITT population on steroids decreased from 47.1% at baseline to 33.3% at Month 60. Among the patients using steroids at baseline the mean (SEM) prednisone-equivalent dose was 0.76 (0.31) mg/kg at baseline, but a prompt tapering of their doses during the first 6 months to 0.15 (0.03) mg/kg was seen. At Month 36 and Month 60 there was a further decline in the prednisone-equivalent dose to 0.08 (0.02) and 0.05 (0.02) mg/kg, respectively. There was a rapid significant decrease of DSSS both in patients not using steroids at all and in patients reducing the steroids dose. The decrease was maintained up to Month 60 (p<0.001 in both subgroups at each follow-up visit). Among the patients reducing the steroid dose, the rate of infections was reduced from 3.4 events/patient year (Year 1) to 1.4 (Year 5).

Conclusion

The use of steroids expressed as mean prednisone equivalent dose decreased from 0.76 mg/kg to 0.05 mg/kg after 5 years of treatment with anakinra. The treatment effect evaluated by DSSS was maintained at the same low level throughout the study.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/steroid-sparing-effect-of-anakinra-kineret-in-the-treatment-of-patients-with-severe-cryopyrin-associated-periodic-syndrome/