Long-Term Safety and Effectiveness of Canakinumab in Patients with MKD/HIDS: Interim Analysis of the RELIANCE Registry

Abstract

Introduction: Interim analysis of the long-term safety and effectiveness of canakinumab, at a patient level, in the mevalonate kinase deficiency/hyperimmunoglobulin-D syndrome (MKD/HIDS) cohort of the RELIANCE registry.

Methods: From June 2018, the RELIANCE registry enrolled paediatric (aged ≥ 2 years) and adult patients (aged ≥ 18 years) with MKD/HIDS who were receiving canakinumab as part of their routine medical care. Safety, physician- and patient-reported measures of disease activity and dosing patterns were evaluated at baseline and every 6 months until end-of-study visit.

Results: At the analysis cut-off date of December 2022, eight patients with MKD/HIDS were enrolled. Five (62.5%) were children (< 18 years) and five (62.5%) were female. The median patient age was 8.0 (range 2.0-39.0) years, and all patients were pre-treated with canakinumab prior to enrolment (median duration of canakinumab treatment: 3.8 years). Canakinumab was well tolerated, with seven (87.5%) patients reporting 48 adverse events (incidence rate/100 patient years: 218.1). No serious adverse drug reactions were reported. Patients continued to receive vaccinations during long-term treatment with canakinumab. Disease activity, evaluated by physician-reported (physician's global assessment, disease remission, C-reactive protein, serum amyloid A, erythrocyte sedimentation rate) and patient-reported (autoinflammatory disease activity index diary, disease activity, fatigue, impact on social life) measures, was generally well controlled throughout the study. Over 50.0% of patients maintained disease remission from baseline to month 24, and medians of all inflammatory markers remained within normal limits throughout the study. Most patients received higher than the recommended starting dose of canakinumab throughout the study.

Conclusion: Data from this interim analysis of a unique registry of patients with a rare disease support the long-term safety and effectiveness of the IL-1-blocking agent canakinumab for the treatment of MKD/HIDS.

Keywords: Autoinflammatory disease; Canakinumab; Fever syndromes; Hyperimmunoglobulin-d syndrome; Mevalonate kinase deficiency.

Fig. 1

Physician-reported outcome measures of disease activity a PGA, b disease remission, c CRP, d SAA and e ESR for the pooled patient cohort and individual patients. CRP C-reactive protein, ESR erythrocyte sedimentation rate, MKD/HIDS mevalonate kinase deficiency/hyperimmunoglobulin-D syndrome, PGA physician’s global assessment, SAA serum amyloid A

Fig. 1

Physician-reported outcome measures of disease activity a PGA, b disease remission, c CRP, d SAA and e ESR for the pooled patient cohort and individual patients. CRP C-reactive protein, ESR erythrocyte sedimentation rate, MKD/HIDS mevalonate kinase deficiency/hyperimmunoglobulin-D syndrome, PGA physician’s global assessment, SAA serum amyloid A

Fig. 1

Physician-reported outcome measures of disease activity a PGA, b disease remission, c CRP, d SAA and e ESR for the pooled patient cohort and individual patients. CRP C-reactive protein, ESR erythrocyte sedimentation rate, MKD/HIDS mevalonate kinase deficiency/hyperimmunoglobulin-D syndrome, PGA physician’s global assessment, SAA serum amyloid A

Fig. 2

Patient-reported outcome measures of disease activity: a AIDAI,* b disease activity, c fatigue and d impact on social life for the pooled patient cohort and individual patients. AIDAI autoinflammatory disease activity index diary, MKD/HIDS mevalonate kinase deficiency/hyperimmunoglobulin-D syndrome, VAS visual analogue scale. *AIDAI scores are collected on a monthly basis. The AIDAI scores presented are for the month preceding the study visit, i.e., values for month 6 are for the month preceding the visit (month 5)

Fig. 2

Patient-reported outcome measures of disease activity: a AIDAI,* b disease activity, c fatigue and d impact on social life for the pooled patient cohort and individual patients. AIDAI autoinflammatory disease activity index diary, MKD/HIDS mevalonate kinase deficiency/hyperimmunoglobulin-D syndrome, VAS visual analogue scale. *AIDAI scores are collected on a monthly basis. The AIDAI scores presented are for the month preceding the study visit, i.e., values for month 6 are for the month preceding the visit (month 5)

Fig. 3

Canakinumab dosing category for the pooled patient cohort and individual patients, q4w every four weeks, SD recommended starting dose. Patients highlighted in grey are aged ≥ 18 years; patient ages are listed in Table 4. The SD of canakinumab was 150 mg or 2 mg per kg of body weight for patients weighing ≤ 40 kg administered subcutaneously q4w. Less than SD (< SD) was defined as < 87.5% of SD and greater than SD (> SD) was defined as > 112.5% of SD. No dosage was documented at month 6 in Patient 7; therefore, an average dose was used when assigning < SD, SD or > SD for this patient at month 6