Cryopyrin-associated periodic syndromes: development of a patient-reported outcomes instrument to assess the pattern and severity of clinical disease activity

ABSTRACT

Objective: Development of an instrument for characterization of symptom patterns and severity in patients with cryopyrin-associated periodic syndromes (CAPS).

Methods: Two generations of daily health assessment forms (DHAFs) were evaluated in this study. The first-generation DHAF queried 11 symptoms. Analyses of results obtained with that instrument identified five symptoms included in a revised second-generation DHAF that was tested for internal consistency and test–retest reliability. This DHAF was also assessed during the initial portion of a phase 3 clinical study of CAPS treatment.

Results: Forty-eight CAPS patients provided data for the first-generation DHAFs. Five symptoms (rash, fever, joint pain, eye redness/pain, and fatigue) were included in the revised second-generation DHAF. Symptom severity was highly variable during all study phases with as many as 89% of patients reporting at least one symptom flare, and percentages of days with flares reaching 58% during evaluation of the second-generation instrument. Mean composite key symptom scores (KSSs) computed during evaluation of the second-generation DHAF correlated well with Physician's Global Assessment of Disease Activity (r = 0.91, p < 0.0001) and patient reports of limitations of daily activities (r = 0.68, p < 0.0001). Test–retest reliability and Cronbach's α‘s were high (0.93 and 0.94, respectively) for the second-generation DHAF. Further evaluation of this DHAF during a baseline period and placebo treatment in a phase 3 clinical study of CAPS patients indicated strong correlations between baseline KSS and Physician's Global Assessment of Disease Activity. Cronbach's α‘s at baseline and test–retest reliability were also high. Potentially important study limitations include small sample size, the lack of a standard tool for CAPS symptom assessment against which to validate the DHAF, and no assessment of the instrument's responsivity to CAPS therapy.

Conclusions: The DHAF is a new instrument that may be useful for capturing symptom patterns and severity in CAPS patients and monitoring responses to therapies for these conditions.

Key Words::

• Cryopyrin-associated periodic syndromes
• Daily health assessment form
• Outcomes instrument

Acknowledgments

Declaration of interest: This study was sponsored and funded by Regeneron Pharmaceuticals, Inc. H.M.H. is a consultant for Regeneron Pharmaceuticals. P.B. and S.J.M. are employees of Regeneron Pharmaceuticals. The authors thank Dr. Raphaela Goldbach-Mansky of NIAMS, NIH for helpful suggestions and the staff of the National Data Bank for Rheumatic Diseases in Wichita, KS, USA for administering the patient evaluations and conducting many of the statistical analyses for this study. The authors also thank Dr. Robert Rhoades, a medical writer at Aesculapius Communications, Inc., for assistance in manuscript preparation.

Notes

* The results of this study were presented in part at a poster session at the November, 2007 Annual Scientific Meeting of the American College of Rheumatology, Boston, MA, USA