Background Autoinflammatory diseases are characterized by recurrent episodes of systemic inflammation with polyarthritis and constitutional symptoms that lead to severe morbidity and disability, as there are no structured therapeutic recommendations for their management. The recognition of the culpable genetic mutations confirms the diagnosis of autoinflammatory syndromes, mainly when the patients do not have pathognomonic clinical characteristics and directs their treatment schedule. Part of the broad spectrum of autoinflammatory syndromes is the periodic fever syndromes, in which inherited or de novo mutations in several genes lead to the increase of IL-1 due to inflammasome activation.
Objectives Investigation of efficacy and safety of Canakinumab in patients with cryopyrin-associated periodic syndrome(CAPS) in adults resistant to treatment with non steroidal anti-inflammatory drugs, systemic corticosteroids, disease modifying anti-rheumatic drugs(DMARDs) and biologic modifiers such as TNF blockers and IL-1 inhibitors1 2.
Methods Retrospective research in the medical records of two University Hospitals in Northern Greece indentified three suitable patients. All 3 presented with recurrent episodes of polyarthritis accompanied by non-specific symptoms as fatigue, myalgia, arthralgia, fever and rash for many years, alongside with increased inflammatory serological markers. Furthermore, they showed substantial lack of response in many therapeutic combinations of different disease modifying anti-rheumatic drugs(DMARDs). One of these patients, due to characteristic rash, recurrent conjuctivitis and childhood onset of symptoms was considered having Familial cold autoinflammatory syndrome(FACS) and therefore no genetic testing was pursued. In the other 2 patients due to the clinical suspicion of autoinflammatory syndrome, molecular genetic analysis for the following 4 genes was performed: MEFV, MVK, TNFRSF1A and NALP3. The same silent mutations pA242A/c.726G>A and pR260R/c.780G>A were found in both patients in homozygosity in exon 3 of the NALP3 gene. Moreover in one of them, the polymorphisms pL411L/c.1231C>T and pS434S/c.1302C>T in heterozygosity in exon 3 of the same gene were also found (all these mutations are not registered in INFEVERS database). All patients received Canakinumab (sc) 150mg every 8 weeks for 6 months. All of them showed clinical remission 2 weeks after the first injection, as well as, reduction of the abnormal values of inflammatory serological markers (decrease of ESR:1st45%, 2nd37%, 3rd80% and decrease of CRP:1st40%, 2nd37%, 3rd 60% respectively). There were no relapses or adverse effects.
Conclusions The immediate and continuous clinical and laboratory remission of these 3 patients showed the favorable therapeutic effect of this monoclonal antibody against IL-1β in patients with CAPS resistant to treatment. It is known that a response to the administration of an IL-1 inhibitor is considered to be a diagnostic criterion of CAPS.
Lachmann HJ.et al N. Engl J. Med 2009;360(23):2416-2425
Kuemmerle-Deschner JB. et al. Ann. Rheum. Dis.2011;70 (12):209
Disclosure of Interest None Declared