BACKGROUND: Targeting interleukin (IL)-6 has become a major therapeutic strategy in the treatment of immune-mediated inflammatory disease. Interference with the IL-6 pathway can be directed at the specific receptor using anti-IL-6Rα antibodies or by directly inhibiting the IL-6 cytokine. This paper is an update of a previous consensus document, based on most recent evidence and expert opinion, that aims to inform on the medical use of interfering with the IL-6 pathway. METHODS: A systematic literature research was performed that focused on IL-6-pathway inhibitors in inflammatory diseases. Evidence was put in context by a large group of international experts and patients in a subsequent consensus process. All were involved in formulating the consensus statements, and in the preparation of this document. RESULTS: The consensus process covered relevant aspects of dosing and populations for different indications of IL-6 pathway inhibitors that are approved across the world, including rheumatoid arthritis, polyarticular-course and systemic juvenile idiopathic arthritis, giant cell arteritis, Takayasu arteritis, adult-onset Still's disease, Castleman's disease, chimeric antigen receptor-T-cell-induced cytokine release syndrome, neuromyelitis optica spectrum disorder and severe COVID-19. Also addressed were other clinical aspects of the use of IL-6 pathway inhibitors, including pretreatment screening, safety, contraindications and monitoring. CONCLUSIONS: The document provides a comprehensive consensus on the use of IL-6 inhibition to treat inflammatory disorders to inform healthcare professionals (including researchers), patients, administrators and payers.

• MeSH
• COVID-19 MeSH
• dospělí MeSH
• interleukin-6 MeSH
• lidé MeSH
• receptory interleukinu-6 * antagonisté a inhibitory   MeSH
• revmatoidní artritida farmakoterapie   MeSH
• Stillova nemoc dospělých farmakoterapie   MeSH
• zánět * farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• konsensus - konference MeSH
• práce podpořená grantem MeSH

OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here we present data from the completed Phase 3 randomised controlled trial (RCT) ORAL Scan (NCT00847613), which evaluated the impact of tofacitinib on patient-reported outcomes (PROs) through 24 months in patients with active RA and inadequate responses to methotrexate (MTX-IR). METHODS: Patients were randomised 4:4:1:1 to receive tofacitinib 5 or 10 mg twice daily (BID), or placebo advanced to tofacitinib 5 or 10 mg, plus background MTX. Patients receiving placebo advanced to tofacitinib at month 3 (non-responders) or month 6 (remaining patients). Mean changes from baseline in PROs, assessed at months 1-24, included Health Assessment Questionnaire-Disability Index, Patient Global Assessment of disease activity (visual analogue scale [VAS]), Patient Assessment of Arthritis Pain (VAS), health-related quality of life (Short Form-36 version 2), Functional Assessment of Chronic Illness Therapy-Fatigue and Medical Outcomes Study-Sleep. RESULTS: Overall, 539/797 (67.6%) patients completed 24 months' treatment. At month 3, tofacitinib-treated patients reported signi cant (p<0.05) mean changes from baseline versus placebo across all PROs, and significantly more patients reported improvements ≥ minimum clinically important differences versus placebo. Improvements in PROs with tofacitinib were sustained to month 24. Following advancement to tofacitinib, placebo-treated patients generally reported changes of similar magnitude to tofacitinib-treated patients. CONCLUSIONS: Patients with RA and MTX-IR receiving tofacitinib 5 or 10 mg BID plus MTX reported significant and clinically meaningful improvements in PROs versus placebo at month 3, which were sustained through 24 months.

• MeSH
• antirevmatika * terapeutické užití   MeSH
• dvojitá slepá metoda MeSH
• hodnocení výsledků péče pacientem MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• methotrexát terapeutické užití   MeSH
• piperidiny MeSH
• pyrimidiny MeSH
• pyrroly terapeutické užití   MeSH
• revmatoidní artritida * diagnostické zobrazování   farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). The phase III, 24-month, placebo-controlled Oral Rheumatoid Arthritis (ORAL) Scan trial was undertaken to evaluate the efficacy, including inhibition of structural progression, and safety of tofacitinib in patients with active RA and an inadequate response to methotrexate (MTX). Month 24 data from the completed study are reported here. METHODS: Patients were randomized 4:4:1:1 to receive tofacitinib 5 mg or 10 mg twice daily, or placebo, switched to tofacitinib 5 mg or 10 mg twice daily, with stable background MTX. Patients receiving placebo switched to tofacitinib at month 3 (nonresponders) or month 6 (remaining patients). Clinical efficacy, structural progression, and treatment-emergent adverse events were evaluated. Analyses were performed on the full analysis set with observed data or nonresponder imputation with no advancement penalty for clinical efficacy, and imputation by linear extrapolation for structural progression. RESULTS: Overall, 797 patients were treated; 539 (67.6%) completed 24 months of treatment. Responses according to the American College of Rheumatology criteria for 20% improvement (ACR20), ACR50, and ACR70; the proportion of patients in whom remission or low disease activity was achieved according to the 4-variable Disease Activity Score in 28 joints using the erythrocyte sedimentation rate, Clinical Disease Activity Index, or Simplified Disease Activity Index; Boolean remission; and Health Assessment Questionnaire disability index scores were maintained from month 12 to 24 and were similar between tofacitinib dosages. Limited structural damage was observed at months 12 and 24. Safety events were similar in type and frequency for both tofacitinib dosages, and were consistent with those previously reported. CONCLUSION: Our findings indicate that clinical and radiographic treatment effects are sustained in months 12-24 in patients with RA receiving tofacitinib 5 mg or 10 mg twice daily plus MTX. The safety profile is consistent with that of other tofacitinib studies.

• MeSH
• antirevmatika terapeutické užití   MeSH
• dospělí MeSH
• inhibitory Janus kinas terapeutické užití   MeSH
• kombinovaná farmakoterapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• methotrexát terapeutické užití   MeSH
• piperidiny terapeutické užití   MeSH
• pyrimidiny terapeutické užití   MeSH
• pyrroly terapeutické užití   MeSH
• revmatoidní artritida diagnostické zobrazování   farmakoterapie   patofyziologie   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
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: The study aimed to assess 52-week efficacy and safety of secukinumab self-administration by autoinjector in patients with active psoriatic arthritis (PsA) in the FUTURE 3 study ( ClinicalTrials.gov NCT01989468). METHODS: Patients (≥ 18 years of age; N = 414) with active PsA were randomized 1:1:1 to subcutaneous (s.c.) secukinumab 300 mg, 150 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and every 4 weeks thereafter. Per clinical response, placebo-treated patients were re-randomized to s.c. secukinumab 300 or 150 mg at week 16 (nonresponders) or week 24 (responders) and stratified at randomization by prior anti-tumor necrosis factor (TNF) therapy (anti-TNF-naïve, 68.1%; intolerant/inadequate response (anti-TNF-IR), 31.9%). The primary endpoint was the proportion of patients achieving at least 20% improvement in American College of Rheumatology response criteria (ACR20) at week 24. Autoinjector usability was evaluated by Self-Injection Assessment Questionnaire (SIAQ). RESULTS: Overall, 92.1% (300 mg), 91.3% (150 mg), and 93.4% (placebo) of patients completed 24 weeks, and 84.9% (300 mg) and 79.7% (150 mg) completed 52 weeks. In the overall population (combined anti-TNF-naïve and anti-TNF-IR), ACR20 response rate at week 24 was significantly higher in secukinumab groups (300 mg, 48.2% (p < 0.0001); 150 mg, 42% (p < 0.0001); placebo, 16.1%) and was sustained through 52 weeks. SIAQ results showed that more than 93% of patients were satisfied/very satisfied with autoinjector usage. Secukinumab was well tolerated with no new or unexpected safety signals reported. CONCLUSIONS: Secukinumab provided sustained improvements in signs and symptoms in active PsA patients through 52 weeks. High acceptability of autoinjector was observed. The safety profile was consistent with that reported previously. TRIAL REGISTRATION: ClinicalTrials.gov NCT01989468 . Registered 21 November 2013. EudraCT 2013-004002-25 . Registered 17 December 2013.

• MeSH
• autoaplikace MeSH
• bolesti hlavy chemicky indukované   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• injekce subkutánní MeSH
• lékové transportní systémy škodlivé účinky   metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky aplikace a dávkování   škodlivé účinky   MeSH
• nazofaryngitida chemicky indukované   MeSH
• psoriatická artritida diagnóza   farmakoterapie   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
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to-or adding-another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.

• MeSH
• antirevmatika terapeutické užití   MeSH
• časové faktory MeSH
• glukokortikoidy terapeutické užití   MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• Janus kinasy antagonisté a inhibitory   MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• methotrexát terapeutické užití   MeSH
• monoklonální protilátky terapeutické užití   MeSH
• náhrada léků MeSH
• revmatoidní artritida farmakoterapie   MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• zapojení pacienta MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH