THU0563 Characterization of A Group of 6 Patients with Mevalonate Kinase Deficiency: Symptoms and Treatment with IL-1 Inhibitors

Abstract

BackgroundMevalonate kinase deficiency (MKD) is a rare autosomal recessive autoinflammatory disease caused by mutations in MVK gene. MKD patients typically have an early onset of symptoms including recurrent episodes of high fever, abdominal pain, diarrhea and vomiting, arthralgia and lymphadenopathy. However not all patients have typical clinical picture of MKD.MethodsWe conducted a retrospective analysis of clinical features of six patients (4 females, 2 males) with MKD (confirmed by identification of MVK gene mutations). Four patients received therapy with inhibitors of IL-1 (Anakinra and/or Canakinumab). One of the patients died from amyloidosis and macrophage activation syndrome (MAS) prior to treatment initiation, her diagnosis was verified post mortem.ResultsAll patients had the first symptoms of disease within the first 6 months of life. During the course of the disease all patients had periodic fever and peripheral lymphadenopathy (mainly cervical group), as well as abdominal pain, nausea/vomiting. Five patients had diarrhea, sometimes with blood, one patient suffered from severe constipation. Rash was seen in five patients, myalgia, artralgia were observed only in four. Oral ulcers were noted in two children. Two patients had neurological involvement. Interestingly, five out of six patients had rhinitis during attacks. One patient during the attack had periorbital edema and hyperemia, which; to our knowledge, have not been reported previously in MKD. One patient developed amyloidosis and MAS before treatment initiation, which led to her death. In patients receiving anti-IL-1 therapy AIDAI index decreased from 49.5±14,6 before to 1,75±1,3 after 6 month of therapy (p=0.003).ConclusionsMKD symptoms can be variable and sometimes atypical, which requires physician's awareness. In our small cohort of MKD patients anti IL-1 therapy was highly effective.Disclosure of InterestNone declared

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

“…70 At long-term follow-up, anakinra showed a 100% CR (online supplementary figure 3A–B). 82 Other observational studies revealed that anakinra decreased the AIDAI score, 83 and attained complete clinical response in 52% and functional status improvement in 81% of patients. 85…”

“…59 Patients who achieved a CR with anakinra ranged from 40% 34 to 100% 82 at long-term follow-up (online supplementary figure 2A–B). Other observational studies showed that anakinra was effective in improving AIDAI score 36 83 or DAS, 57 58 in attaining disease control, 73 clinical/biochemical remission, 84 85 complete/partial resolution of CAPS symptoms, 38 43 45 49 51 60 62 64 79 PROs, 36 58 79 85 CHQ-PF50 60 and DLQI. 64 Seven studies also demonstrated improvement or stabilisation with anakinra in neurological outcomes (eg, migrainous headache, papilledema), 45 60 62 hearing loss, 30 55– 57 60 62 and visual acuity.…”

“…59 Patients who achieved a CR with canakinumab ranged from 62% 48 to 93% 59 at mid-term follow-up, and 50% 34 52 to 100% 82 at long-term follow-up (online supplementary figure 2A–B). Other observational studies have also shown the effectiveness of canakinumab in improving the Disease Activity Score (DAS), 57 65 Autoinflammatory Disease Activity Index (AIDAI) score, 36 83 complete/partial resolution of symptoms, 38 45 88 improvement in physician/patient assessed PROs 36 65 85 and the Child Health Assessment Questionnaire (CHAQ). 65 Of the eight studies assessing other outcomes, 23 42 45 47 55– 57 65 treatment with canakinumab was associated with improvement or stabilisation in neurological outcomes (eg, migrainous headache), 23 42 45 hearing loss, 23 42 55– 57 65 vision outcomes (eg, uveitis, conjunctivitis) 23 47 and musculoskeletal outcomes.…”

“…Eleven observational studies 69 70 75 78 82 83 85 86 90 93 94 provided data on the effectiveness of anakinra in HIDS/MKD. Among the studies reporting CR/PR, 11% 70 to 30% 86 of anakinra-treated patients achieved a CR at mid-term follow-up, whereas 78% achieved a PR.…”