Cryopyrin-associated periodic syndromes: development of a patient-reported outcomes instrument to assess the pattern and severity of clinical disease activity.
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 alpha'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 alpha'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.
Hoffman
Hal M
HM
University of California at San Diego, La Jolla, CA 92093-0635, USA. hahoffman@ucsd.edu
Wolfe
Frederick
F
Belomestnov
Pavel
P
Mellis
Scott J
SJ
D002352:Carrier Proteins / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017063:Outcome Assessment, Health Care; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D013577:Syndrome
D002352:Carrier Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human