ORCID Profile
0000-0002-4537-6015
Current Organisation
Charité – Universitätsmedizin Berlin
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Publisher: The Journal of Rheumatology
Date: 11-2022
Abstract: Axial involvement in patients with psoriatic arthritis (PsA) is a common subset of this condition, but a unanimous definition has yet to be established. It has been defined by using different criteria, ranging from the presence of at least unilateral grade 2 sacroiliitis to those used for ankylosing spondylitis (AS), or simply the presence of inflammatory low back pain (IBP). Our aim was to identify and evaluate the efficacy of therapeutic interventions for treatment of axial disease in PsA. This systematic review is an update of the axial PsA (axPsA) domain of the treatment recommendations project by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). The systematic review of the literature showed that new biologic and targeted synthetic disease-modifying antirheumatic drug classes, namely interleukin (IL)-17A and Janus kinase inhibitors, could be considered for the treatment of axPsA. This would be in addition to previously recommended treatments such as nonsteroidal antiinflammatory drugs, physiotherapy, simple analgesia, and tumor necrosis factor inhibitors. Conflicting evidence still remains regarding the use of IL-12/23 and IL-23 inhibitors. Further studies are needed for a better understanding of the treatment of axPsA, as well as validated outcome measures.
Publisher: Springer Science and Business Media LLC
Date: 05-09-2022
DOI: 10.1186/S13063-022-06589-Y
Abstract: Axial involvement constitutes a specific domain of psoriatic arthritis (PsA). Interleukin (IL)-23 inhibitors have demonstrated improvement in axial PsA (axPsA) symptoms, but have not shown efficacy in treating ankylosing spondylitis (AS), suggesting differences in axPsA processes and treatments. In a post hoc, pooled analysis of patients with investigator- and imaging-confirmed sacroiliitis in two phase 3, randomized, placebo-controlled studies (DISCOVER-1 and DISCOVER-2), patients treated with guselkumab, an IL-23p19 inhibitor, had greater axial symptom improvements compared with placebo. Confirmatory imaging at baseline was restricted to the sacroiliac (SI) joints, occurred prior to/at screening, and was locally read. The STAR study will prospectively assess efficacy outcomes in PsA patients with magnetic resonance imaging (MRI)-confirmed axial inflammation. Eligible, biologic-naïve patients with PsA ( N = 405) for ≥ 6 months and active disease (≥ 3 swollen and ≥ 3 tender joints, C-reactive protein [CRP] ≥ 0.3 mg/dL) despite prior non-biologic disease-modifying antirheumatic drugs, apremilast, and/or nonsteroidal anti-inflammatory drugs will be randomized (1:1:1) to guselkumab every 4 weeks (Q4W) guselkumab at week (W) 0, W4, then every 8 weeks (Q8W) or placebo with crossover to guselkumab at W24, W28, then Q8W. Patients will have Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4, spinal pain component score (0–10 visual analog scale) ≥ 4, and screening MRI-confirmed axial involvement (positive spine and/or SI joints according to centrally read Spondyloarthritis Research Consortium of Canada [SPARCC] score ≥ 3 in ≥ 1 region). The primary endpoint is mean change from baseline in BASDAI at W24 multiplicity controlled secondary endpoints at W24 include AS Disease Activity Score employing CRP (ASDAS), Disease Activity Index for PsA (DAPSA), Health Assessment Questionnaire – Disability Index (HAQ-DI), Investigator’s Global Assessment of skin disease (IGA), and mean changes from baseline in MRI SI joint SPARCC scores. Centrally read MRIs of spine and SI joints (scored using SPARCC) will be obtained at W0, W24, and W52, with readers blinded to treatment group and timepoint. Treatment group comparisons will be performed using a Cochran-Mantel-Haenszel or chi-square test for binary endpoints and analysis of covariance, mixed model for repeated measures, or constrained longitudinal data analysis for continuous endpoints. This study will evaluate the ability of guselkumab to reduce both axial symptoms and inflammation in patients with active PsA. This trial was registered at ClinicalTrials.gov, NCT04929210 , on 18 June 2021. Protocol version: Version 1.0 dated 14 April 2021.
Publisher: Wiley
Date: 10-03-2022
DOI: 10.1002/ACR.24517
Abstract: To investigate the longer‐term effects of secukinumab 150 mg on fatigue in patients with ankylosing spondylitis (AS) in the MEASURE 1 study (up to 3 years) and the MEASURE 2 study (up to 2 years). Patients with active AS were randomized to secukinumab or placebo in MEASURE 1 (10 mg/kg intravenous [IV] followed by 150 mg subcutaneous) and MEASURE 2 (150 mg subcutaneous). Patients were naive to treatment with anti–tumor necrosis factor (anti‐TNF‐naive) therapy or had an inadequate response/intolerance to anti‐TNF therapy (anti‐TNF‐IR). Fatigue was measured using the Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT‐F) scale. Relationships between fatigue response and baseline characteristics and clinical/laboratory variables were explored. Significant improvements in FACIT‐F scores from baseline were observed with secukinumab across both studies versus placebo at week 16 ( P 0.05). Improvements were sustained through week 156 (MEASURE 1) and week 104 (MEASURE 2). Significantly more patients reported fatigue responses (FACIT‐F improvement ≥4 observed data) with secukinumab 150 mg than with placebo at week 16 in both MEASURE 1 ( P 0.05) and MEASURE 2 ( P 0.01). Fatigue responses were achieved by 75.6% of patients receiving secukinumab at week 156 (MEASURE 1) and 81.4% at week 104 (MEASURE 2) these results were consistent in patients who were anti‐TNF‐naive (74.3% and 84.6%, respectively) and anti‐TNF‐IR (81.3% and 75.0%, respectively). Baseline characteristics did not predict improvement in fatigue consistently. Fatigue responses were moderately to strongly correlated with responses in several clinical measures, including the Assessment of SpondyloArthritis international Society (ASAS) 20%/40% improvement, ASAS5/6 responses, the Ankylosing Spondylitis Disease Activity Score with C‐reactive protein level, the Bath Ankylosing Spondylitis Disease Activity Index, and the Short Form 36 health questionnaire scores. Secukinumab provided rapid and sustained improvements in fatigue for up to 3 years, regardless of prior anti‐TNF exposure.
Publisher: Oxford University Press (OUP)
Date: 19-12-2020
DOI: 10.1093/RHEUMATOLOGY/KEY375
Abstract: To evaluate the effect of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, on efficacy, imaging outcomes, and safety through 4 years (208 weeks) in patients with ankylosing spondylitis. Patients opting to enrol had completed 2 years’ treatment in the MEASURE 1 core study with subcutaneous secukinumab 150 or 75 mg every 4 weeks (q4Wk), following intravenous loading to Week (Wk) 4, or placebo treatment to Wk16/24. Up-titration from secukinumab 75–150 mg q4Wk was permitted following a protocol amendment. Efficacy is reported for patients originally randomized to secukinumab. Radiographic changes were assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and changes in MRI measures of inflammation using the Berlin scoring method. Safety and tolerability were evaluated. Among 274 extension study participants, 89.7% (78/87) and 93.0% (93/100) originally randomized to secukinumab 150 and 75 mg, respectively, completed 208Wk. Through Wk208, Assessment of Spondyloarthritis International Society 20/40 (observed) were 79.7%/60.8% (150 mg), 71.0%/43.5% (75 mg) and 80.0%/76% (up-titrators n = 25). Mean (s.d.) changes in mSASSS were 1.2 (3.91) (150 mg), 1.8 (4.32) (75 mg) and 1.6 (5.67) (up-titrators). No radiographic progression (mSASSS change from Baseline 2) was observed in 79% of patients receiving either secukinumab dose. Exposure-adjusted incidence rates per 100 patient-years were: serious infections (1.0), Candida infections (0.4), Crohn’s disease (0.6), ulcerative colitis (0.2), and malignant/unspecified tumours (0.5), with no new safety signals. Through 4 years, secukinumab provided sustained efficacy on signs and symptoms, and MRI outcomes, a low rate of radiographic progression and a consistent safety profile. NCT01863732.
Publisher: BMJ
Date: 29-04-2022
No related grants have been discovered for Denis Poddubnyy.