Canakinumab controls disease activity in periodic fever syndromes, JIA

Audrey Abella
25 Jul 2018

The human anti-interleukin (IL)-1β monoclonal antibody canakinumab continued to show optimal control of disease activity (ie, one or no new flare, no uptitration) in patients with colchicine-resistant familial Mediterranean fever (crFMF), TNF* receptor-associated periodic syndrome (TRAPS), and hyper IgD** syndrome (HIDS)/mevalonate kinase deficiency (MKD) after 112 weeks, according to results from the fourth phase of the CLUSTER*** trial presented at EULAR 2018.

The CLUSTER trial involved four phases of study periods, with phase 2 initially evaluating the efficacy of canakinumab 150/300 mg Q4W in generating a complete response (no flares) for 16 weeks, while the 24-week phase 3 assessed whether reducing the dosing frequency of canakinumab to Q8W will sustain clinical efficacy. Phase 4 evaluated the long-term efficacy of canakinumab 150 mg or 300 mg, both given Q4W or Q8W for another 72 weeks. [EULAR 2018, abstract THU0570]

At week 112, a substantial proportion of patients with crFMF and TRAPS maintained optimal disease control with the 150-mg Q8W regimen (40.4 percent and 50.4 percent, respectively). Although 50 percent of HIDS/MKD cases were effectively managed by the 300-mg Q4W regimen, optimal disease control was also observed in 22 percent of patients who received canakinumab 150 mg Q8W, which supports the efficacy of canakinumab 150 mg Q8W in controlling disease activity, said the researchers.

Overall disease control rates were 96.6 percent, 94.3 percent, and 83.3 percent for crFMF, TRAPS, and HIDS/MKD, respectively. Majority of patients across all cohorts had a Physician Global Assessment of <2 (no or minimal disease activity). Median SAA# levels rapidly decreased from baseline and remained suppressed through phase 4 (from 618 to 21 mg/L, from 243 to 12 mg/L, and from 2,061 to 16 mg/L, respectively).

A retrospective analysis of a Turkish cohort also showed the potential of canakinumab in controlling attacks in patients with crFMF (n=18). Three patients directly received canakinumab, while 15 were switched from anakinra. Median duration of canakinumab use was 8 months. Two patients received canakinumab 300 mg/month while the rest were given 150 mg/month. [EULAR 2018, abstract SAT0611]

Participants who received canakinumab had significant improvement in the severity (Visual Analogue Scale score, 3.5 vs 8.5; p<0.01), duration (24 vs 108 hours; p<0.01), and frequency (1 vs 6; p<0.01) of FMF attacks, as well as C-reactive protein (4.2 vs 35.8 mg/L; p<0.01) and erythrocyte sedimentation rates (12 vs 38 mm/hour; p<0.01) compared with those who remained on colchicine. Five patients achieved complete remission.


Potential in paediatric arthritis

A Japanese study saw the potential of canakinumab in the management of systemic juvenile idiopathic arthritis (SJIA). Participants who had inadequate response to prior treatment (n=19, mean age 9.9 years) received open-label canakinumab 4 mg/kg (maximum 300 mg) Q4W for 28 weeks. Of these, 78.9 percent received tocilizumab. [EULAR 2018, abstract THU0599]

At week 8, all participants achieved aACR30/50/70##. Of those with prior tocilizumab exposure, 80 percent achieved aACR100 and 73.7 percent achieved corticosteroid tapering.

At week 28, 73.7 percent of the overall population achieved corticosteroid tapering, and 10.5 percent were steroid-free.

The incidence of SJIA is higher in Japan than in Europe and the US, with a reported incidence of almost 42 percent and a persistently high disease activity and/or intolerability to tocilizumab, the only approved biologic treatment for SJIA in Japan. [Annual report on children with chronic refractory diseases from the Japanese Ministry of Health, Labour, and Welfare 2008;102-113] Therefore, the improvement in disease activity and reduction of oral steroid dose in this trial suggest that canakinumab may be an alternative to tocilizumab, said the researchers.

Taken together, the findings of these trials underscore the role of canakinumab in the management of autoinflammatory syndromes and paediatric arthritis.


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