Results from CAPS Survey Prove Decrease of QoL in Patients and Caregivers

Because cryopyrin-associated periodic syndrome (CAPS) is an ultra-rare disease, information about the quality of life (QoL) of patients and caregivers affected by the condition is limited.

Historically, the human monoclonoal antibody canakinumab has been used in increasing frequency for the treatment of CAPS, but knowledge of the disease’s societal impact is still largely unknown. An observational study in Dutch CAPS patients was conducted by Catharina M. Mulders-Manders and colleagues, and results were published in the Orphanet Journal for Rare Diseases.¹

The primary endpoint of the study was to quantify quality of life (QoL) in patients with CAPS. The secondary endpoint was assessment of the larger societal impact of CAPS on patient’s work and school.

The article, titled, “Decreased quality of life and societal impact of cryopyrin-associated periodic syndrome treated with canakinumab: a questionnaire based cohort study,” focused on answers provided by patients in a questionnaire regarding treatment with canakinumab at baseline and retrospectively. QoL was evaluated using the EQ-5D-5L in adults and CHQ-PF50 in children.

CAPS is the result of autosomal dominant mutations in the gene encoding the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 protein (NLRP3). The protein creates the cornerstone of the NLRP3-inflammasome, a protein complex involved in the innate immune system. Activation of the NLRP3-inflammasome leads to overproduction and activation of the pro-inflammatory cytokine interleukin-1 beta (IL-1β). Because they can inhibit IL-1, canakinumab and anakinra have been known as the most effective treatment options for CAPS.

Individuals impacted by this genetic mutation typically experience recurrent or continuous inflammation associated with fever, arthralgia or arthritis, skin rash, neurologic abnormalities, and a variety of other symptoms. While the efficacy and side effects for the 2 aforementioned drugs are comparable, treatment with canakinumab is more than 10 times as costly as treatment with anakinra.

Forty total CAPS patients were identified during the study, 31 of which were adults (77.5%), 5 adolescents aged 12 years to 18 years (12.5%), and 4 children younger than 12 years (10.0%). Twenty patients (50%) were male, and 24 of the 40 CAPS patients (60.0%) were included in the study. Median age at the start of the study was 28.5 years (range 5—82 years), and over 50% of patients had CAPS-related complications. Of the 24 patients included in the study, 17 completed the QoL questionairres and could be included in the analysis: 3 children, 2 adolescents and 12 adults.

At baseline, adults and adolescents receiving canakinumab (n=14) reported an average EQ-5D-5L QoL of 0.769. The minimum EQ-5D score was 0.296, observed in a single male patient. No patients reported to have extreme issues on any of the dimensions of the EQ-5D. For both self-care and anxiety/depression, 86% of patients reported no problems. Conversely, 86% of patients did report to have a problem on the pain and discomfort dimension. The 5 pediatric patients reported average scores on HQ-physical (51.1) and CHQ-psychosocial (57.1) that are similar to the standardized score in the general US population (50).

For the 8 patients who completed the questionnaire recalling their experiences during treatment with anakinra, treatment with anakinra had been stopped when treatment with canakinumab was initiated. The median time between the stop of anakinra and the questionnaire was 49.5 months (range 1-76 months). Three patients reported a higher QoL during canakinumab treatment, while 2 patients reported higher QoL during treatment with anakinra. Three patients reported no difference during both treatment.

A total of 5 patients were attending school: 3 went to primary school, 1 to secondary school, and 1 to higher education. Each patient had called in sick at least 1 day (average 2.9 days) in a 4-week period. Among the 6 adult patients with paid jobs, each had been absent from work in a 4 week period, with an average of 8.7 days.

On average, the 6 caregivers who participated provided 9 hours of caregiving per week, an 83% derived a lot of fulfillment from providing informal care. None reported severe problems, and 3 reported mental health problems related to their caregiving. Overall, caregiver QoL was strongly and positively correlated with patients’ QoL.

With this information, it was concluded that adequate disease control and attention to societal impact of CAPS and its treatment are critical to the care for those afflicted by the condition.

In the video below, Len Walt, Vice President and Head of Medical Affairs at Sobi in North America discusses neonatal-onset multisystem inflammatory disease (NOMID), one of the 3 variations of CAPS, and why it’s so difficult to diagnose.

References:

1. Mulders-Manders CM, et al. Decreased quality of life and societal impact of cryopyrin-associated periodic syndrome treated with canakinumab: a questionnaire based cohort study. Orphanet Journal of Rare Diseases. 2018;13:59. doi: 10.1186/s13023-018-0799-1.