BACKGROUND: Treat-to-target (T2T) is a widely accepted strategy for patients with rheumatoid arthritis (RA). It recommends attaining a goal of at least low disease activity (LDA) within 6 months; otherwise, the current therapy should be modified. We aimed to investigate whether switching a first-line targeted therapy (TT) in patients not reaching LDA within 6 months leads to a higher probability of meeting LDA at the 12-month visit in daily clinical practice using data from Czech registry ATTRA. METHODS: We included patients with RA starting the first-line TT from 1 January 2012 to 31 January 2017 with at least 1-year follow-up. We created four mutually exclusive cohorts based on (1) switching to another TT within the first year and (2) reaching a treatment target (DAS28-ESR ≤ 3.2) at the 6-month visit. The primary outcome was the comparison of odds for reaching remission (REM) or LDA at the 12-month visit between patients switching and not switching TT after not reaching treatment target at 6 months. Before using logistic regression to estimate the odds ratio, we employed the propensity score to match patients at the 6-month visit. RESULTS: A total of 1275 patients were eligible for the analysis. Sixty-two patients switched within the first 5 months of the treatment before evaluating treatment response at the 6-month visit (C1); 598 patients reached the treatment target within 6 months of therapy (C2); 124 patients did not reach treatment response at 6-month visit and switched to another therapy (C3), and 491 patients continued with the same treatment despite not reaching LDA at the 6-month visit (C4). We matched 75 patients from cohort C3 and 75 patients from C4 using the propensity score. Patients following the T2T principle (C3) showed 2.8 (95% CI 1.4-5.8; p = 0.005) times increased likelihood of achieving REM/LDA at the 12-month visit compared to patients not following the T2T strategy (C4). CONCLUSIONS: In daily clinical practice, the application of the T2T strategy is underused. Switching TT after not reaching REM/LDA within the first 6 months leads to a higher probability of achieving REM/LDA in RA patients at the 12-month visit.

• Klíčová slova
• Propensity score, Registry, Rheumatoid arthritis, Treat-to-target,
• MeSH
• antirevmatika * terapeutické užití   MeSH
• indukce remise MeSH
• lidé MeSH
• registrace MeSH
• stupeň závažnosti nemoci MeSH
• tendenční skóre MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antirevmatika * MeSH

OBJECTIVE: The 24-week equivalent efficacy and comparable safety results of the biosimilar SB5 and reference adalimumab (ADA) from the phase III randomized study in patients with moderate-to-severe rheumatoid arthritis (RA) have been reported previously. We undertook this transition study to evaluate patients who switched from ADA to SB5 or who continued to receive SB5 or ADA up to 52 weeks. METHODS: In this phase III study, patients were initially randomized 1:1 to receive SB5 or ADA (40 mg subcutaneously every other week). At 24 weeks, patients receiving ADA were rerandomized 1:1 to continue with ADA (ADA/ADA group) or to switch to SB5 (ADA/SB5 group) up to week 52; patients receiving SB5 continued with SB5 for 52 weeks (SB5 group). Efficacy, safety, and immunogenicity were evaluated up to 52 weeks. RESULTS: The full analysis set population consisted of 542 patients (269 in the SB5 group, 273 in the ADA overall group [patients who were randomized to receive ADA at week 0], 125 in the ADA/SB5 group, and 129 in the ADA/ADA group). The percentages of patients meeting the American College of Rheumatology 20%, 50%, or 70% improvement criteria (achieving an ACR20, ACR50, or ACR70 response) at week 24 were maintained after the transition from ADA to SB5, and these response rates were comparable across treatment groups throughout the study. ACR20 response rates ranged from 73.4% to 78.8% at week 52. Radiographic progression was minimal and comparable across treatment groups. The safety profile and the incidence of antidrug antibodies were comparable across treatment groups after transition. CONCLUSION: SB5 was well tolerated over 1 year in patients with RA, with efficacy, safety, and immunogenicity comparable to those of ADA. Switching from ADA to SB5 had no treatment-emergent issues such as increased adverse events, increased immunogenicity, or loss of efficacy.

• MeSH
• adalimumab aplikace a dávkování   MeSH
• antirevmatika aplikace a dávkování   MeSH
• biosimilární léčivé přípravky aplikace a dávkování   MeSH
• časové faktory MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• náhrada léků * MeSH
• revmatoidní artritida farmakoterapie   MeSH
• stupeň závažnosti nemoci 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
• Názvy látek
• adalimumab MeSH
• antirevmatika MeSH
• biosimilární léčivé přípravky MeSH

OBJECTIVE: SB5 is a biosimilar agent for adalimumab (ADA). The aim of this study was to evaluate the efficacy, pharmacokinetics (PK), safety, and immunogenicity of SB5 in comparison with reference ADA in patients with rheumatoid arthritis (RA). METHODS: In this phase III, randomized, double-blind, parallel-group study, patients with moderately to severely active RA despite treatment with methotrexate were randomized 1:1 to receive SB5 or reference ADA at a dosage of 40 mg subcutaneously every other week. The primary efficacy end point was the response rate based on the American College of Rheumatology 20% improvement criteria (ACR20) at week 24 in the per-protocol set (completer analysis). Additional end points included efficacy, PK, safety, and immunogenicity assessments. RESULTS: Of the 544 patients randomized to receive a study drug, the full analysis set comprised 542 patients (269 in the SB5 group, 273 in the reference ADA group) and the per-protocol set comprised 476 patients (239 receiving SB5, 237 receiving reference ADA). The ACR20 response rate at week 24 in the per-protocol set was equivalent between those receiving SB5 and those receiving reference ADA (72.4% and 72.2%, respectively); the difference in the ACR20 response rate (0.1%, [95% confidence interval -7.83%, 8.13%]) was within the predefined equivalence margin (±15%). Similar results were seen in the full analysis set (missing data being considered a nonresponse). The SB5 and reference ADA treatment groups were comparable across other end points, including the ACR 50% and ACR 70% improvement response rates, Disease Activity Score in 28 joints based on the erythrocyte sedimentation rate, PK data, incidence of treatment-emergent adverse events, and the antidrug antibody response. Subgroup analyses showed that the efficacy and safety of SB5 and reference ADA were comparable regardless of antidrug antibody status. CONCLUSION: The ACR20 response rate at week 24 was equivalent between patients treated with the biosimilar agent SB5 and those treated with reference ADA. SB5 and reference ADA were both well tolerated, with comparable safety profiles, in patients with RA.

• MeSH
• adalimumab škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• antirevmatika škodlivé účinky   terapeutické užití   MeSH
• biosimilární léčivé přípravky škodlivé účinky   farmakokinetika   terapeutické užití   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• revmatoidní artritida farmakoterapie   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• adalimumab MeSH
• antirevmatika MeSH
• biosimilární léčivé přípravky MeSH

OBJECTIVE: This 24-week, phase IIb, double-blind study was undertaken to evaluate the efficacy and safety of mavrilimumab (a monoclonal antibody to granulocyte-macrophage colony-stimulating factor receptor α) and golimumab (a monoclonal antibody to tumor necrosis factor [anti-TNF]) in patients with rheumatoid arthritis (RA) who have had an inadequate response to disease-modifying antirheumatic drugs (DMARDs) (referred to as DMARD-IR) and/or inadequate response to other anti-TNF agents (referred to as anti-TNF-IR). METHODS: Patients with active RA and a history of DMARD-IR (≥1 failed regimen) or DMARD-IR (≥1 failed regimen) and anti-TNF-IR (1-2 failed regimens) were randomized 1:1 to receive either mavrilimumab 100 mg subcutaneously every other week or golimumab 50 mg subcutaneously every 4 weeks alternating with placebo every 4 weeks, administered concomitantly with methotrexate. The primary end points were the American College of Rheumatology 20% improvement (ACR20), 50% improvement, and 70% improvement response rates at week 24, percentage of patients achieving a Disease Activity Score in 28 joints using C-reactive protein level (DAS28-CRP) of <2.6 at week 24, percentage of patients with a score improvement of >0.22 on the Health Assessment Questionnaire (HAQ) disability index (DI) at week 24, and safety/tolerability measures. This study was not powered to formally compare the 2 treatments. RESULTS: At week 24, differences in the ACR20, ACR50, and ACR70 response rates between the mavrilimumab treatment group (n = 70) and golimumab treatment group (n = 68) were as follows: in all patients, -3.5% (90% confidence interval [90% CI] -16.8, 9.8), -8.6% (90% CI -22.0, 4.8), and -9.8% (90% CI -21.1, 1.4), respectively; in the anti-TNF-IR group, 11.1% (90% CI -7.8, 29.9), -8.7% (90% CI -28.1, 10.7), and -0.7% (90% CI -18.0, 16.7), respectively. Differences in the percentage of patients achieving a DAS28-CRP of <2.6 at week 24 between the mavrilimumab and golimumab groups were -11.6% (90% CI -23.2, 0.0) in all patients, and -4.0% (90% CI -20.9, 12.9) in the anti-TNF-IR group. The percentage of patients achieving a >0.22 improvement in the HAQ DI score at week 24 was similar between the treatment groups. Treatment-emergent adverse events were reported in 51.4% of mavrilimumab-treated patients and 42.6% of golimumab-treated patients. No deaths were reported, and no specific safety signals were identified. CONCLUSION: The findings of this study demonstrate the clinical efficacy of both treatments, mavrilimumab at a dosage of 100 mg every other week and golimumab at a dosage of 50 mg every 4 weeks, in patients with RA. Both regimens were well-tolerated in patients who had shown an inadequate response to DMARDs and/or other anti-TNF agents.

• MeSH
• antirevmatika škodlivé účinky   terapeutické užití   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• humanizované monoklonální protilátky MeSH
• lidé středního věku MeSH
• lidé MeSH
• methotrexát terapeutické užití   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• monoklonální protilátky škodlivé účinky   terapeutické užití   MeSH
• revmatoidní artritida farmakoterapie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antirevmatika MeSH
• golimumab MeSH Prohlížeč
• humanizované monoklonální protilátky MeSH
• mavrilimumab MeSH Prohlížeč
• methotrexát MeSH
• monoklonální protilátky MeSH
• TNF-alfa MeSH

BACKGROUND: Calprotectin may be a sensitive biomarker of rheumatoid arthritis (RA) disease activity. OBJECTIVES: In the current study, we investigated whether calprotectin is a better biomarker than CRP for predicting clinical activity and ultrasound parameters in patients with RA. METHODS: A total of 160 patients with RA underwent clinical (swollen joint count-SJC, tender joint count-TJC, Disease Activity Score-DAS28, Clinical Disease Activity Index-CDAI, and simplified Disease Activity Index-SDAI) and ultrasound (German US7) examination. Clinical and laboratory measures were correlated with ultrasound findings using Spearman´s correlation coefficient. Differences in serum calprotectin levels in patients with variable disease activity according to the DAS28-ESR and CDAI scores were assessed using ANOVA. Multivariate regression analysis was used to determine the predictive values of calprotectin, CRP and SJC for CDAI and PD US synovitis scores. RESULTS: Serum calprotectin was significantly associated with DAS28-ESR (r = 0.321, p<0.001), DAS28-CRP (r = 0.346, p<0.001), SDAI (r = 0.305, p<0.001), CDAI (r = 0.279, p<0.001) scores and CRP levels (r = 0.556, p<0.001). Moreover, calprotectin was significantly correlated with GS (r = 0.379, p<0.001) and PD synovitis scores (r = 0.419, p<0.001). The multivariate regression analysis showed that calprotectin is a better predictor of the CDAI score and PD US synovitis than CRP. CONCLUSIONS: The results of this study support an additional role of calprotectin in assessing inflammatory activity in patients with RA.

• MeSH
• C-reaktivní protein metabolismus   MeSH
• dospělí MeSH
• kohortové studie MeSH
• leukocytární L1-antigenní komplex krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• revmatoidní artritida krev   diagnostické zobrazování   patologie   MeSH
• ultrasonografie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• C-reaktivní protein MeSH
• leukocytární L1-antigenní komplex MeSH

OBJECTIVE: Clinical remission in some patients with rheumatoid arthritis (RA) may be associated with ongoing synovial inflammation that is not always detectable on clinical examination or reflected by laboratory tests but can be visualized by musculoskeletal ultrasound. The goal of our study was to determine the levels of serum calprotectin, a major leukocyte protein, in patients with RA in clinical remission and to investigate the ability of serum calprotectin levels to distinguish patients in ultrasound-defined remission from those with residual ultrasound subclinical inflammation. METHODS: Seventy RA patients in clinical remission underwent clinical and ultrasound examination. Ultrasound examination was performed according to the German US7 score. Ultrasound remission was defined as grey scale (GS) range 0-1 and power Doppler (PD) range 0. The levels of serum calprotectin and C-reactive protein (CRP) were determined. The discriminatory capacity of calprotectin and CRP in detecting residual ultrasound inflammation was assessed using ROC curves. RESULTS: The total number of patients fulfilling the DAS28-ESR, DAS28-CRP, SDAI and CDAI remission criteria was 58, 67, 32 and 31, respectively. Residual synovial inflammation was found in 58-67% of the patients who fulfilled at least one set of clinical remission criteria. Calprotectin levels were significantly higher in patients with residual synovial inflammation than in those with ultrasound-defined remission (mean 2.5±1.3 vs. 1.7±0.8 μg/mL, p<0.005). Using ultrasound-defined remission criteria, calprotectin had an AUC of 0.692, p<0.05 using DAS28-ESR remission criteria and an AUC of 0.712, p<0.005 using DAS28-CRP remission criteria. Calprotectin correctly distinguished ultrasound remission from subclinical activity in 70% of patients. CRP (AUC DAS28-ESR = 0.494, p = NS; AUC DAS28-CRP = 0.498, p = NS) had lower and insignificant discriminatory capacity. CONCLUSION: The present study demonstrates the potential of calprotectin to distinguish RA patients in both clinical and ultrasound-defined remission from patients in clinical remission but with residual subclinical disease activity.

• MeSH
• C-reaktivní protein analýza   MeSH
• dospělí MeSH
• leukocytární L1-antigenní komplex krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• revmatoidní artritida krev   diagnostické zobrazování   MeSH
• reziduální nádor MeSH
• senioři MeSH
• ultrasonografie MeSH
• zánět krev   diagnostické zobrazování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• C-reaktivní protein MeSH
• leukocytární L1-antigenní komplex MeSH

INTRODUCTION: Calprotectin, a heterodimeric complex of S100A8/9 (MRP8/14), has been proposed as an important serum biomarker that reflects disease activity and structural joint damage in rheumatoid arthritis (RA). The objective of this cross-sectional study was to test the hypothesis that calprotectin is associated with clinical and ultrasound-determined disease activity in patients with RA. METHODS: A total of 37 patients with RA (including 24 females, a mean disease duration of 20 months) underwent a clinical examination and 7-joint ultrasound score (German US-7) of the clinically dominant hand and foot to assess synovitis by grey-scale (GS) and synovial vascularity by power Doppler (PD) ultrasound using semiquantitative 0-3 grading. The levels of serum calprotectin and C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were determined at the time of the ultrasound assessment. We analysed the relationship between serum calprotectin level, traditional inflammatory markers, and ultrasound-determined synovitis. RESULTS: The levels of serum calprotectin were significantly correlated with swollen joint count (r = 0.465, p < 0.005), DAS28-ESR (r = 0.430, p < 0.01), ESR (r = 0.370, p < 0.05) and, in particular, CRP (r = 0.629, p < 0.001). Calprotectin was significantly associated with GS (r = 0.359, p < 0.05) and PD synovitis scores (r = 0.497, p < 0.005). Using multivariate regression analysis, calprotectin, adjusted for age and sex, was a better predictor of PD synovitis score (R(2) = 0.765, p < 0.001) than CRP (R(2) = 0.496, p < 0.001). CONCLUSIONS: The serum levels of calprotectin are significantly associated with clinical, laboratory and ultrasound assessments of RA disease activity. These results suggest that calprotectin might be superior to CRP for monitoring ultrasound-determined synovial inflammation in RA patients.

• MeSH
• biologické markery krev   MeSH
• C-reaktivní protein metabolismus   MeSH
• dospělí MeSH
• krevní sedimentace MeSH
• leukocytární L1-antigenní komplex krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• průřezové studie MeSH
• reprodukovatelnost výsledků MeSH
• revmatoidní artritida krev   diagnóza   diagnostické zobrazování   MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• stupeň závažnosti nemoci MeSH
• synovitida krev   diagnóza   diagnostické zobrazování   MeSH
• ultrasonografie dopplerovská metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• C-reaktivní protein MeSH
• leukocytární L1-antigenní komplex MeSH

Biologics have mainly been assessed in patients with severe rheumatoid arthritis (RA) globally. Less attention has been paid to moderately active disease, especially in Central and Eastern Europe (CEE). Access to biologics and the disease features of RA patients may differ in CEE, relative to other regions. We assessed the clinical and patient-reported outcomes (PROs) of treatment from CEE patients in the multinational PRESERVE study ( NCT00565409 ). Patients with moderate RA 28-joint disease activity score ((DAS28) erythrocyte sedimentation rate (ESR) >3.2 and ≤5.1) despite methotrexate (MTX) treatment received open-label etanercept (ETN) 50 mg QW + MTX for 36 weeks. Low disease activity (DAS28 low disease activity (LDA) ≤3.2) and remission (DAS28 ESR <2.6) were assessed. PROs included Health Assessment Questionnaire Disability Index (HAQ-DI), patient global assessment (PGA), EuroQol-5 Dimension (EQ-5D), pain visual analogue scale (VAS), Medical Outcomes Study sleep questionnaire (MOS Sleep), Functional Assessment of Chronic Illness Therapy (FACIT), and Work Productivity and Activity Impairment for RA (WPAI-RA). Descriptive summary statistics were employed. Of the 834 enrolled patients, 302 were from CEE. At baseline, CEE patients had similar disease states versus the overall population. By week 36, LDA was achieved by 87 %, remission by 67 %, and normal HAQ-DI (≤0.5) by 53 % of patients. Mean scores (SDs) for PROs significantly improved by week 36 as follows: HAQ-DI total by -0.6 (0.5); PGA by -2.4 (2.1); EQ-5D total index by 0.2 (0.2). Pain VAS, MOS Sleep, FACIT, and WPAI-RA also showed significant improvements. In conclusion, induction therapy with ETN + MTX led to DAS28 LDA, remission, and improvements in PROs in most CEE patients with moderately active RA despite treatment with MTX. These results are similar to the overall study population in the PRESERVE trial.

• MeSH
• antirevmatika aplikace a dávkování   MeSH
• aplikace orální MeSH
• činnosti denního života MeSH
• dospělí MeSH
• etanercept MeSH
• imunoglobulin G aplikace a dávkování   MeSH
• indukce remise MeSH
• krevní sedimentace MeSH
• lidé středního věku MeSH
• lidé MeSH
• methotrexát aplikace a dávkování   MeSH
• průzkumy a dotazníky MeSH
• receptory TNF aplikace a dávkování   MeSH
• revmatoidní artritida farmakoterapie   MeSH
• rozvrh dávkování léků MeSH
• senioři MeSH
• spánek MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• východní Evropa MeSH
• Názvy látek
• antirevmatika MeSH
• etanercept MeSH
• imunoglobulin G MeSH
• methotrexát MeSH
• receptory TNF MeSH