Search

Julia Berman,1,2,* Victoria Furer,2,3,* Mark Berman,2,3 Ofer Isakov,1,2 Devy Zisman,4,5 Amir Haddad,4 Ori Elkayam2,3 1Department of Medicine ‘T’, Sourasky Medical Center, Tel Aviv, Israel; 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Department of Rheumatology, Sourasky Medical Center, Tel Aviv, Israel; 4Rheumatology Unit, Carmel Medical Center, Haifa, Israel; 5The Ruth and Bruce Rappaport Faculty of Medicine,Technion, Haifa, Israel*These authors contributed equally to this workCorrespondence: Julia Berman Email juliab@tlvmc.gov.ilObjective: To assess the clinical response to ixekizumab following secukinumab failure in patients with psoriatic arthritis.Methods: A retrospective multi-center observational study included psoriatic arthritis (PsA) patients with a history of treatment with secukinumab, further treated with ixekizumab. Primary endpoint was primary response to treatment (drug survival > 6 months); secondary endpoints were changes in disease activity indices from initiation of ixekizumab to 6 and 12 months later and overall drug survival.Results: Of 23 PsA patients, 86% (n = 20) received more than two TNF inhibitors (TNFi). Median secukinumab treatment time was 15 months (IQR 10– 21.5 months). Subsequently, 19 patients (83%) had a primary response to ixekizumab. Overall treatment duration during follow-up period for primary responders was 14 months (IQR 10– 20.5). Reasons for ixekizumab cessation were worsening psoriasis (27%), peripheral arthritis (27%), both (47%), worsening of axial disease (13%), and adverse events (6%). Articular disease indices including Disease Activity Index for Psoriatic Arthritis (DAPSA), tender joints count (TJC) and Simplified Disease Activity Index (SDAI) were significantly lower at 6 and 12 months (DAPSA 1.5– 2 levels reduction; p = 0.018 and 1– 1.5 levels reduction; p = 0.031, respectively; TJC − 2.16 [− 4.0, − 0.3]; p = 0.025 and − 1.69 [− 3.09, − 0.28]; p = 0.022, respectively; SDAI − 10.13 [− 16.4, − 3.8], p = 0.003 and − 12.2 [− 17.1, − 7.2], p = 0.0002, respectively). PASI75 at 6 and 12 months was achieved by 63% and 57%, respectively, and PASI100 at 6 and 12 months by 31% and 21%, respectively.Conclusion: Patients with resistant PsA, including inadequate response to secukinumab, demonstrated a good response to ixekizumab, albeit limited on time. Within class switch from secukinumab to ixekizumab may be a plausible therapeutic option in PsA patients following secukinumab failure.Keywords: secukinumab, ixekizumab, arthritis, psoriatic, duration of therapy, antibodies, monoclonal, humanized, psoriasis

To investigate the effects of methotrexate (MTX) and the tumour necrosis factor inhibitor infliximab (IFX) on immune cells derived from peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) of inflammatory arthritis patients. Phytohaemagglutinin (PHA)-induced proliferation of healthy donors' PBMCs and synovial intermediate monocytes (CD14+CD16+ cells) in SFMCs derived from psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients was determined by flow cytometry following co-culture with IFX and MTX. PHA-induced interferon-γ (IFN-γ) production in PBMCs was measured by enzyme-linked immunosorbent assay. The drugs' effect on mRNA expression in SFMCs was determined by quantitative polymerase chain reaction. The combination of IFX 10 μg/mL + MTX 0.1 μg/mL had the strongest inhibitory effect on PBMC proliferation (91%), followed by MTX 0.1 μg/mL (86%) and IFX 10 μg/mL (49%). In PHA-stimulated PBMCs, IFN-γ production was reduced by IFX 10 μg/mL, MTX 0.1 μg/mL, and IFX 10 μg/mL + MTX 0.1 μg/mL by 68%, 90%, and 85%, respectively. In SFMCs, IFX 10 µg/mL significantly reduced CD14+CD16+ cells compared to medium (PsA 54%, p < 0.01; RA 46%, p < 0.05), while MTX had no effect on this population. IFX + MTX led to a similar suppression of CD14+CD16+ cells as achieved by IFX alone. The drugs had different impacts on SFMC gene expression. Both IFX and MTX effectively inhibited PBMC proliferation and IFN-γ production, but only IFX reduced synovial monocytes and pro-inflammatory gene expression in SFMCs, suggesting a differential impact of IFX and MTX on critical inflammatory cell populations ex vivo. [ABSTRACT FROM AUTHOR]