Long-term safety and effectiveness of canakinumab in patients with monogenic autoinflammatory diseases: results from the interim analysis of the RELIANCE registry

Abstract

Objective: Interim analysis of the RELIANCE registry, an on-going, non-interventional, open-label, multicentre, prospective study evaluating the long-term safety, dosing regimens and effectiveness of canakinumab in patients with cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), tumour-necrosis factor receptor-associated periodic syndrome (TRAPS) or mevalonate-kinase deficiency (MKD)/hyperimmunoglobulin-D syndrome (HIDS).

Methods: From September 2017 for patients with CAPS, and June 2018 for patients with FMF, TRAPS or MKD/HIDS, the registry enrolled paediatric (aged ≥2 years) and adult patients (aged ≥18 years) receiving canakinumab as part of their routine medical care. Safety, canakinumab dose, disease activity and quality of life outcome measures were evaluated at baseline and every 6 months until end of study visit.

Results: At the analysis cut-off date (December 2020), 168 patients (91 CAPS, 54 FMF, 16 TRAPS and 7 MKD/HIDS) were enrolled. 85 (50.9%) patients were female and 72 (43.1%) were children (<18 years). The median patient age was 20.0 years (range 2.0-79.0 years). In the CAPS cohort, serious infections and serious adverse drug-reactions were more common in patients receiving higher than the recommended starting dose (SD) of canakinumab. A trend to receive >SD of canakinumab was observed in the pooled population. The majority of patients were reported as having either absent or mild/moderate disease activity (physician's global assessment) from baseline to Month 30, with a stable proportion of patients (~70%) in remission under canakinumab treatment. Patient-reported disease activity (Visual Analogue Scale (VAS), Autoinflammatory Disease Activity Index), fatigue (VAS); markers of inflammation (C-reactive protein, serum amyloid A and erythrocyte sedimentation rate) remained well-controlled throughout.

Conclusion: Data from this analysis confirm the long-term safety and effectiveness of canakinumab for the treatment of CAPS, FMF, TRAPS and MKD/HIDS.

Keywords: Cryopyrin-Associated Periodic Syndromes; Familial Mediterranean Fever; Inflammation.

Figure 1

Study design. Treatment decisions were determined by the treating physician according to standard of care and local clinical practice. CAPS, cryopyrin-associated periodic syndromes; EOS, end of study; FMF, familial Mediterranean fever; MKD/HIDS, mevalonate kinase deficiency/hyperimmunoglobulin D syndrome; qXw, every X weeks; TRAPS, tumour necrosis factor receptor-associated periodic syndrome.

Figure 2

Canakinumab dosing category in (A) pooled population and individual disease cohorts (B) CAPS, (C) FMF, (D) TRAPS, (E) MKD/HIDS. (A) Data were missing for 20, 16, 12, 14, 14, 14 patients at BL, Months 6, 12, 18, 24 and 30, respectively; (B) Data were missing for 11, 9, 7, 9, 8, 8 patients at BL, Months 6, 12, 18, 24 and 30, respectively; (C) Data were missing for 7, 5, 3, 3, 4 patients at BL, Months 6, 12, 18 and 24, respectively; (D) Data were missing for 1, 1, 1, 1 patients at BL, Months 6, 12 and 18, respectively; (E) Data were missing for 1, 1, 1, 1 patients at BL, Months 6, 12 and 18, respectively. The SD of canakinumab was defined as 150 mg (or 2 mg/kg of body weight for patients weighing ≤40 kg) q8w for patients with CAPS, or q4w for patients with FMF, TRAPS or MKD/HIDS. SD was defined as canakinumab >170 mg q4w for with FMF, MKD/HIDS and TRAPS; >170 mg q8w for patients with CAPS. BL, baseline; CAPS, cryopyrin-associated periodic syndromes; FMF, familial Mediterranean fever; MKD/HIDS, mevalonate kinase deficiency/hyperimmunoglobulin D syndrome; qXw, every X weeks; SD, recommended starting dose; TRAPS, tumour necrosis factor receptor-associated periodic syndrome.

Figure 3

PGA of disease activity in the pooled population. Data were missing for 18, 14, 11, 5 patients at Baseline, Month 6, 12 and 18, respectively. PGA, physician’s global assessment.

Figure 4

Physician’s assessment of disease remission in the pooled population and individual disease cohorts (CAPS, FMF, TRAPS, MKD/HIDS). N=1 for the MKD/HIDS cohort at Month 24; as the patient was not in disease remission, the proportion is reported as 0%. CAPS, cryopyrin-associated periodic syndromes; FMF, familial Mediterranean fever; MKD/HIDS, mevalonate kinase deficiency/hyperimmunoglobulin D syndrome; TRAPS, tumour necrosis factor receptor-associated periodic syndrome.

Figure 5

Median AIDAI score distribution over time in the (A) pooled population and individual disease cohorts (B) CAPS versus NOMID/CINCA subgroup*, (C) FMF versus patients without prior canakinumab therapy, (D) TRAPS and (E) MKD/HIDS. Active disease was defined as a total AIDAI score ≥9. *Includes patients diagnosed with MWS/NOMID, NOMID/CINCA, NOMID or CINCA; †No data were available for the patient cohort at this time point. AIDAI, autoinflammatory disease activity index diary; CAN, canakinumab; CAPS, cryopyrin-associated periodic syndromes; FMF, familial Mediterranean fever; MWS, Muckle-Wells syndrome; NOMID/CINCA, neonatal-onset multisystem inflammatory disease/chronic infantile neurological cutaneous articular syndrome; MKD/HIDS, mevalonate kinase deficiency/hyperimmunoglobulin D syndrome; TRAPS, tumour necrosis factor receptor-associated periodic syndrome.