OBJECTIVE: Our goal was to assess the efficacy and safety of intravenous (IV) secukinumab for the treatment of adults with active axial spondyloarthritis (axSpA) in INVIGORATE-1. METHODS: INVIGORATE-1 (NCT04156620) was a randomized, double-blind, parallel-group, phase 3 trial in patients with active axSpA (either radiographic or nonradiographic). Patients were randomized one to one to receive IV secukinumab (6 mg/kg at baseline followed by 3 mg/kg every four weeks) or IV placebo for 16 weeks. After week 16, patients randomized to placebo were switched to IV secukinumab (3 mg/kg every four weeks), and patients randomized to secukinumab continued treatment through week 52. The primary endpoint was the Assessment of SpondyloArthritis International Society (ASAS40) response at week 16. Safety was evaluated through week 60. RESULTS: Among patients initially randomized to IV secukinumab (n = 264) or placebo (n = 262), 86.0% and 88.9% completed the entire 60-week study period, respectively. A higher proportion of patients receiving secukinumab versus placebo met the primary endpoint (ASAS40 response) at week 16 (40.9% vs 22.9%; P < 0.0001). By week 24, patients who switched from placebo to secukinumab at week 16 achieved ASAS40 response rates comparable to those in patients originally randomized to secukinumab. All secondary efficacy endpoints were met at week 16, and responses were sustained through week 52. No new or unexpected safety signals were observed with IV secukinumab. CONCLUSION: IV secukinumab was effective for the treatment of adults with active axSpA over 52 weeks. The safety profile was consistent with that in previous reports on subcutaneous secukinumab.

• MeSH
• antirevmatika * terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• axiální spondyloartritida * farmakoterapie   diagnostické zobrazování   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• humanizované monoklonální protilátky * MeSH
• intravenózní infuze MeSH
• intravenózní podání MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky * terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antirevmatika * MeSH
• humanizované monoklonální protilátky * MeSH
• monoklonální protilátky * MeSH
• secukinumab MeSH Prohlížeč

OBJECTIVE: To investigate real-world effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA) and the association with (i) treatment line (second and third TNFi-series) and (ii) reason for withdrawal from the preceding TNFi [lack of efficacy (LOE) vs adverse events (AE)]. METHODS: Prospectively collected routine care data from 12 European registries were pooled. Rates for 12-month drug retention and 6-month remission [Ankylosing Spondylitis Disease Activity Score C-reactive protein inactive disease (ASDAS-ID)] were assessed in second and third TNFi-series and stratified by withdrawal reason. RESULTS: We included 8254 s and 2939 third TNFi-series; 12-month drug retention rates were similar (71%). Six-month ASDAS-ID rates were higher for the second (23%) than third TNFi (16%). Twelve-month drug retention rates for patients withdrawing from the preceding TNFi due to AE vs LOE were similar for the second (68% and 67%) and third TNFi (both 68%), while for the second TNFi, rates were lower in primary than secondary non-responders (LOE <26 vs ≥26 weeks) (58% vs 71%, P < 0.001). Six-month ASDAS-ID rates for the second TNFi were higher if the withdrawal reason was AE (27%) vs LOE (17%), P < 0.001, while similar for the third TNFi (19% vs 13%, P = 0.20). CONCLUSION: A similar proportion of axSpA patients remained on a second and third TNFi after one year, but with low remission rates for the third TNFi. Remission rates on the second TNFi (but not the third) were higher if the withdrawal reason from the preceding TNFi was AE vs LOE.

• Klíčová slova
• adverse events, axial spondyloarthritis, effectiveness, lack of efficacy, switching TNF-inhibitors,
• MeSH
• antirevmatika terapeutické užití   MeSH
• axiální spondyloartritida * farmakoterapie   MeSH
• dospělí MeSH
• indukce remise MeSH
• inhibitory TNF terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• náhrada léků * MeSH
• prospektivní studie MeSH
• registrace MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• antirevmatika MeSH
• inhibitory TNF MeSH
• TNF-alfa MeSH

INTRODUCTION: The administration of biologic disease-modifying antirheumatic drugs, including tumor necrosis factor (TNF)-α inhibitors, is observed to interfere with the disease activity and progression. In this study, we aimed to assess the effectiveness and response predictors of adalimumab (ADA), a TNF-α blocker, in patients with axial spondyloarthritis (AxSpA). METHODS: This study was a historical prospective, registry-based observational study on patients with AxSpA treated with first-line ADA after conventional drug failure. For evaluation and comparison, patients were divided into three groups according to the number of years from AxSpA diagnosis to initiation of ADA treatment: (A) <5 years, (B) 5-10 years, and (C) >10 years. The assessment instruments ankylosing spondylitis disease activity score (ASDAS), Bath ankylosing spondylitis activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), health assessment questionnaire (HAQ), Short Form 36 questionnaire (SF-36), and EuroQoL 5 dimension questionnaire (EQ-5D) were regularly administered for up to 24 months of follow-up. RESULTS: This study included 1043 patients with AxSpA (9.2% with non-radiographic AxSpA, 68.9% men). By month 6, a significantly higher proportion of patients with ASDAS remission (<1.3) was achieved upon earlier intervention in group A (30.1%) and B (32.9%) than in the late intervention group C (22.6%) (p ⩽ 0.05). At month 6, lower age and better BASFI at treatment initiation were identified as the strongest predictors of ASDAS remission in both univariable [odds ratio (OR): 0.956, p ⩽ 0.001; OR: 0.834, p ⩽ 0.001, respectively] and multivariable analyses (OR: 0.963, p ⩽ 0.001; OR: 0.859, p ⩽ 0.001, respectively). Earlier intervention also led to improvement in most patient-reported outcomes (PROs) based on HAQ, SF-36, and EQ-5D. CONCLUSION: Results from the ATTRA registry concur with previous clinical trials that supported efficacy of TNF-α blockers and showed better treatment outcomes with early interventions, including reduction of disease activity and improvement in PROs. We identified age and BASFI as the main factors influencing treatment effectiveness.

• Klíčová slova
• adalimumab, ankylosing spondylitis, axial spondyloarthritis, disease activity, patient-reported outcomes,
• Publikační typ
• časopisecké články MeSH