FRI0489 Canakinumab Improves Patient Reported Outcomes in Patients with Periodic Fever Syndromes: Table 1.

Abstract

BackgroundPeriodic Fever Syndromes (PFS) are rare autoinflammatory conditions including Familial Mediterranean Fever (FMF), Hyper-IgD Syndrome/ Mevalonate Kinase Deficiency (HIDS/MKD), and TNF-Receptor Associated Periodic Syndrome (TRAPS).1 It has been shown that colchicine-resistant FMF (crFMF), HIDS/MKD and TRAPS considerably impact physical and emotional aspects of patients' lives.2–4 Open label studies suggested that canakinumab (CAN), a fully human and highly specific anti-IL-1β monoclonal antibody, is efficacious in crFMF, HIDS/MKD and TRAPS.5–7 To date, there is no data showing the effect of CAN on Health-Related Quality of Life (HRQoL) in PFS patients.ObjectivesTo evaluate the effect of CAN on HRQoL using Child Health Questionnaire – Parent Form 50 (CHQ-PF50) and SF-12 Health Survey (SF-12) in PFS patients.MethodsIn a Phase 3 randomised placebo controlled study of CAN in PFS (NCT02059291), SF-12 Physical Component Summary (PCS) and Mental Component Summary (MCS) were assessed in adults. For children (>5–<18 years), CHQ-PF50 Physical (PhS) and Psychosocial (PsS) Summary scores were assessed.Results181 patients were randomised to CAN or placebo in 3 cohorts (63 crFMF, 72 MKD/HIDS, 46 TRAPS). 71 adults ≥18 years and 110 children (age range ≥2–<18 years). Patients reported early clinically meaningful improvement in SF-12 PCS scores reported at Week (Wk) 5 which were sustained and increased to a large effect size by Wk 16 for all indications (Table). Similarly, clinically meaningful improvements in SF-12 MCS, CHQ-PF50 PhS and PsS was observed in all indications, with the exception of PsS in HIDS/MKD and TRAPS patients (Table).Table 1.Patient reported outcomesMean change from baseline (n/N)crFMFHIDS/MKDTRAPSWeek 5Week 16Week 5Week 16Week 5Week 16SF-12 PCS7.9 (29/30)9.55 (30/31)13.81 (15/15)13.81 (14/14)9.63 (16/17)11.64 (13/14)SF-12 MCS4.83 (29/30)4.27 (30/31)6.41 (15/15)8.14 (14/14)5.65 (16/17)5.51 (13/14)CHQ-PF50 PhS13.2 (21/24)20.1 (18/21)5.5 (32/34)9.9 (27/29)7.4 (16/18)14.9 (13/14)CHQ-PF50 PsS4.1 (21/24)7.2 (18/21)1.8* (32/34)5.2 (27/29)0.9* (16/18)1.2* (13/14)N = total number of patients; n = patients who received at least one dose of canakinumab. *Minimal important difference8,9from baseline was not achieved.ConclusionsCanakinumab showed rapid improvement by Week 5 in patient reported outcomes in adults and children with PFS, which was sustained through Week 16.ReferencesSavic S. and Wood P. Clin. Med. 2011;11(4):396–401Dandekar P, et al. Pediatr. Rheumatol. 13(S1):P22Dandekar P, et al. Pediatr. Rheumatol. 13(S1):P23Dandekar P, et al. Pediatr. Rheumatol. 13(S1):P24Brik R, et al. Arthritis Rheumatol. 2014;66(11):3241–3Arostegui, J.I, et al. Arthritis Rheumatol. 2015; 67 (S10)Gattorno M, et al. Arthritis Rheumatol. 2015; 67 (S10)User's manual for the SF-12v2 Health Survey, 3rd ed. 2012Cohen J, et. al. Statistical Power Analysis for the Behavioural Sciences,2nd ed. 1988Disclosure of InterestH. Lachmann Consultant for: Novartis, SOBI, Takeda, GSK, Speakers bureau: Novartis, SOBI, A. Simon Grant/research suppo...

Systematic literature review of efficacy/effectiveness and safety of current therapies for the treatment of cryopyrin-associated periodic syndrome, hyperimmunoglobulin D syndrome and tumour necrosis factor receptor-associated periodic syndrome

“…19 The HRQoL assessments revealed that canakinumab treatment led to early clinically meaningful improvements in SF-12 Physical Component Summary (PCS), CHQ-PF50 Physical Subscale (PhS) and CHQ-PF50 Psychosocial Subscale (PsS) scores at week 5, which were sustained and increased to a large effect size by week 16. 20 In an open-label, 3-part non-RCT, all HIDS/MKD patients achieved a CR with canakinumab during 6-month treatment period. 26 Disease relapsed in 78% of patients during the canakinumab withdrawal period.…”

“…19 In HRQoL assessments, canakinumab provided early clinically meaningful improvements in SF-12 PCS, CHQ-PF50 PhS and CHQ-PF50 PsS scores at week 5, which were sustained and increased in magnitude by week 16. 20 In the Phase II non-RCT, 19/20 patients (95%) with active recurrent/chronic TRAPS achieved a CR with canakinumab. 27 Disease relapsed in all patients during canakinumab withdrawal period, but similar responses were attained and sustained on retreatment with canakinumab.…”

“…One RCT, 17– 20 one non-RCT 26 and five observational studies 69 72 78 86 93 provided evidence for canakinumab in HIDS/MKD. In a pivotal Phase III RCT (CLUSTER trial) 17 with three cohorts of patients, including 72 patients with HIDS/MKD, patients achieving a clinical response (ie, resolution of index flare at Day 15 and no new disease flare over 16 weeks of treatment) at week 16 were significantly higher with canakinumab (35%) vs placebo (6%), 17 with 40% of canakinumab-treated patients achieving inactive disease (ie, AIDAI score <9).…”

“…One RCT, 17– 20 one non-RCT 27 and four observational studies 82 86– 88 comprised evidence for canakinumab. In the TRAPS cohort of CLUSTER trial described above, 17– 20 a significantly higher proportion of canakinumab-treated patients achieved the clinical response than placebo (45% vs 8%), 17 with 46% of patients achieving inactive disease at week 16. 18 The clinical response at week 40 was also numerically higher with canakinumab vs placebo (75% vs 40%; table 2).…”

Hereditary periodic fever syndromes in adult rheumatology practice

“…По мнению авторов, результаты исследования доказывают патогенную роль ИЛ1β при этих заболеваниях. И у взрослых, и у детей отмечалось су-щественное улучшение показателей, отражающих физи-ческий и ментальный компонент качества жизни [44]. Эффективность, хорошая переносимость терапии инги-биторами ИЛ1, в частности канакинумабом, наблюдались также у пациентов с FMF, перенесших трансплантацию донорской почки [45].…”