AB0774 TREATMENT WITH IL-1 INHIBITORS IN PATIENTS WITH SCHNITZLER’S SYNDROME: A 5-YEAR CLINICAL EXPERIENCE
Authors: S. Salugina, V. Gorodetskiy, E. Fedorov, V. Rameev, E. Borzova, N. Lopatina
Journal: Annals of the Rheumatic Diseases (2021)

Background: Schnitzler’s syndrome (SchS) is a rare non-monogenic auto-inflammatory disease (AID) which manifests in adults and is characterized by recurrent urticarial lesions, monoclonal gammopathy, and other manifestations of a systemic inflammatory response (fever, muscle / joint / bone pains, leukocytosis, increased ESR, CRP). Off-label treatment with IL-1 inhibitors (anakinra, canakinumab) was shown to be highly effective and well tolerated in pts with SchS based on a few multicenter studies and practical experience. Objectives: To analyze a real-life experience of the treatment with IL-1 inhibitors in pts with SchS in the rheumatology tertiary care settings. Methods: The study included 7 pts (3 women, 4 men) with treated with IL-1 inhibitors (anakinra, canakinumab). A median age at the diagnosis was 44 years old (25 – 68). Age at the disease onset ranged from 22 to 66. All pts met the Strasbourg diagnostic criteria. 7 pts received canakinumab, while 3 pts were first treated with anakinra followed by a switch to canakinumab. Anakinra was administered subcutaneously 100 mg per day. Canakinumab was given subcutaneously at a dosage of 150 mg every 8 weeks. The treatment duration with anakinra ranged from 1 week to 2.5 months with further switching to canakinumab. The duration of canakinumab treatment by the time of analysis ranged from 2 months to 5.5 years. Results: All pts at the inclusion into the study suffered from urticarial rash, pains in bones and joints, fatigue, fever (6), increased acute phase marker levels (ESR, CRP), monoclonal gammopathy, mainly IgMk (4.7 – 9 g/l). An average period between the disease onset and the treatment initiation was 3 years (2 to 4). In all pts lymphoproliferative diseases and monogenic AIDs (CAPS, TRAPS) were excluded. Before the treatment with IL-1 inhibitors, all pts had received NSAIDs and/or GCs, methotrexate - 2, plaquenil-2. During the treatment with IL-1 inhibitors, 6 out of 7 pts had a complete response as demonstrated by a symptom resolution within several days and a rapid decrease in ESR and CRP levels. In 3 pts, who responded anakinra, the treatment was switched to canakinumab. In one patient with a partial response to anakinra, there was a loss of the effect upon switching to canakinumab, In one patient, the interval between canakinumab injections was increased up to 5 months without a symptom relapse. This patient fathered a healthy child whilst on treatment with canakinumab. The therapy was well tolerated in all pts, no SAE were noted. Table 1. Clinical and demographic characteristics of patients with SchS Patients 1 2 3 4 5 6 7 Sex M F M F F M M Age (y) 44 32 56 68 25 51 49 Age of disease onset (y) 40 29 53 66 22 39 47 Urticarial rash + + + + + + + Fever + - + + + + + Fatigue + + + + + + + Bone pain + + + + + + + Arthralgia/arthritis + + + + + + + ESR(normal &lt;15mm/h) 31 140 100 49 81 53 56 CRP (normal &lt;5mg/л) 107 44 192 96 369 76 41,82 IgM kappa (g/l) 7,1-5,2 4,7-7,8 7,6 - - 5,2 9 IgM lambda(g/l) - - 1,36 - - - - IgG kappa (g/l) - - - 5,1 - - - IgG lambda (g/l) - - - - 10,7 - - Conclusion: SchS is a rare disease that occurs in the practice of a rheumatologist. Short and long acting IL-1 inhibitors are highly efficient and safe treatment options for pts with SchS. A switching from short to long acting IL-1 inhibitors can be effective in SchS pts. References: [1]Krause K, Tsianakas A, Wagner N, Fischer J, Weller K, Metz M, et al. Efficacy and safety of canakinumab in Schnitzler syndrome: a multicenter randomized placebo-controlled study. J Allergy Clin Immunol 2017;139:1311-20. [2]Betrains A., Staelsa F, Vanderschueren S. Efficacy and safety of canakinumab treatment in schnitzler syndrome: A systematic literature review Seminars in Arthritis and Rheumatism 50 (2020) 636-642. Disclosure of Interests: None declared