ABSTRACT
BackgroundOlokizumab (OKZ), an IL-6 ligand inhibitor in doses of 64 mg every two weeks (q2w) or every 4 weeks (q4w) demonstrated significant improvements in signs and symptoms of RA. Due to lack of availability of the IL-6 receptor antagonists tocilizumab and sarilumab in the pandemic COVID-19 situation, RA patients (pts) were switched to OKZ as a registered drug in Russia in 2022.ObjectivesTo investigate safety and efficacy of OKZ after switching from an IL-6 receptor inhibitor in clinical practice.MethodsThis retrospective cohort study included available efficacy and safety data of OKZ in pts with RA after switching from tocilizumab (IV or SC) or sarilumab (SC) from 11 of participating centers.Efficacy assessments and routine biochemical data were analyzed using descriptive statistics – mean with standard deviation for continuous parameters and absolute and relative frequency for binary variables. AE were reported by participating centers according to pt's files. The statistical significance of data of the analyzed variable at a particular visit compared with previous visits or with the Switch visit was determined using paired t-test. Fisher's exact test or chi-square test was used to compare the proportion of pts with improvement/no change and worsening. All tests were 2-tailed, and a p-value <0.050 was considered statistically significant. As this is an observational study, the statistical criteria have not been pre-specified and therefore the data presented cannot be considered definitive but should be confirmed in future analyses.ResultsEfficacy and safety results were collected for 110 RA pts with a mean age of 47.8 (15.7) years, including 87 (79.1%) women. 77 (70.0%) pts were RF/ACPA positive. Mean RA duration was 13.1 (8.9) years and mean duration of treatment with an IL-6 receptor antagonist was 47.8 (30.0) months. Mean interval before switching was 54.7 (35.4) days with the main reason of unavailable IL6-R antagonist. Pts were treated with OKZ 64 mg q4w SC.Before initiation of OKZ, an increase of DAS28-CRP was observed due to a prolonged period after the last injection of the IL-6R inhibitor from 2.8 to 3.1 weeks in 32 pts on monotherapy who were transferred to OKZ faster (on average after 41.6 (23.8) days), and from 2.7 to 3.3 weeks in 73 pts on concomitant sDMARDs (60.0 (38.0) days). DAS28-CRP was improved to 2.8 on the second OKZ visit (S+1) in both groups. Response to OKZ was maintained over a period of 2 months with no difference between pts previously receiving an IL-6 R antagonist. Of note, lower disease activity based on DAS28-CRP of 2.5 and 2.6 was achieved after 8 weeks (S+2) of OKZ therapy compared to the previous IL-6R inhibitors treatment S-1 visit (P less 0.05) (Figure 1).Figure 1.Mean DAS28CRP over time, M(SD)[Figure omitted. See PDF]Abbreviation: S-2 and S-1 last visits before switching– S+1 and S+2 visits after switching,Treatment emergent AE occurred in 7 (6.4%) pts, the most common AE in 3 pts (2.7%) included arthralgia of hands and feet and transient leukopenia in 2 (1.8%) pts.Serious AE were reported by 1 (0.9%) pt (exacerbation of herpes infection that led to treatment discontinuation). No deaths were reported. There were no apparent differences in safety and efficacy outcomes between pts on OKZ monotherapy compared to combined treatment with csDMARDs. Only one pt was switched back to tocilizumab when it became available.Table 1.Summary of treatment emergent adverse events (safety population)NOKZ 64 mg q4w with MTX N=78OKZ 64 mg q4w monotherapy N=32Any AE51 carpal canal syndromeAny serious AE10Any AE leading to discontinuation of study drug10Any death00Any AE of special interest10Infections10Laboratory abnormalitiesHyperbilirubin-emiaALT, AST elevation less than 3 ULNALT, alanine transaminase;AST, aspartate transaminase;ULN, upper limit of normalConclusionIn pts with RA responding to an IL-6R antagonist, switching to OKZ was safe and well tolerated in clinical practice. The treatment response was maintained and in some pts disease activity moderately decreased in compariso to baseline level both in OKZ mono and combination therapy.Reference[1]J.Smolen, N Engl J Med 2022;387:715-726AcknowledgementsI have acknowledgements to Vinogradova I.B., Anoshenkova O.N., Antipova O.V., Baranov A.A., Bogdanova E.A., Grabovetskaya Y.Y., Ilivanova E.P.,Kalyagin A.N., Kushnir I.N., Lapkina N.A. Mokrousova M.V., Nesmeyanova O.B., Nikitina N.V., Shesternya P.A. and Yudina N.V.Disclosure of InterestsEugen Feist Consultant of: Abbvie, Eli Lilly, Galapagos, Medac, Novartis, Sanofi, Sobi, R-Pharm, Grant/research support from: Eli Lilly, Novartis, Pfizer, Evgeny Nasonov Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer.
ABSTRACT
Still's disease in children (systemic juvenile idiopathic arthritis - JIA) and adult Still's disease (ASD) are considered as systemic autoinflammatory diseases of unknown etiology, which are based on similar immunopathogenetic mechanisms associated with genetically determined disorders of the mechanisms of innate immunity. ASD was first described 50 years ago by the English rheumatologist Eric George Lapthorne Bywaters. The molecular basis of ASD immunopathogenesis is the activation of innate immunity associated with NLRP3 inflammasome-dependent mechanisms of inflammation, characterized by the overproduction of "pro-inflammatory" cytokines - interleukin (IL) 1 and IL-18, inducing the synthesis of other proinflammatory inflammatory mediators. A review of new data concerning the mechanisms of immunopathology, clinical polymorphism, laboratory biomarkers and the possibilities of ASD pharmacotherapy is presented. Particular attention is paid to the prospects for the use of monoclonal antibodies to IL-1beta - canakinumab. The problems associated with the generality of clinical and laboratory disorders, pathogenetic mechanisms and pharmacotherapy of ASD and coronavirus disease 2019 (COVID-19) are considered.Copyright © 2021 Authors. All rights reserved.
ABSTRACT
Still's disease in children (systemic juvenile idiopathic arthritis - JIA) and adult Still's disease (ASD) are considered as systemic autoinflammatory diseases of unknown etiology, which are based on similar immunopathogenetic mechanisms associated with genetically determined disorders of the mechanisms of innate immunity. ASD was first described 50 years ago by the English rheumatologist Eric George Lapthorne Bywaters. The molecular basis of ASD immunopathogenesis is the activation of innate immunity associated with NLRP3 inflammasome-dependent mechanisms of inflammation, characterized by the overproduction of "pro-inflammatory" cytokines - interleukin (IL) 1 and IL-18, inducing the synthesis of other proinflammatory inflammatory mediators. A review of new data concerning the mechanisms of immunopathology, clinical polymorphism, laboratory biomarkers and the possibilities of ASD pharmacotherapy is presented. Particular attention is paid to the prospects for the use of monoclonal antibodies to IL-1beta - canakinumab. The problems associated with the generality of clinical and laboratory disorders, pathogenetic mechanisms and pharmacotherapy of ASD and coronavirus disease 2019 (COVID-19) are considered.Copyright © 2021 Authors. All rights reserved.