Methotrexate plus ustekinumab versus ustekinumab monotherapy in patients with active psoriatic arthritis (MUST): a randomised, multicentre, placebo-controlled, phase 3b, non-inferiority trial.

Background: The role of methotrexate in combination with biological agents in patients with psoriatic arthritis remains unclear. The MUST phase 3b trial aimed to compare the efficacy of ustekinumab plus placebo with ustekinumab plus methotrexate in patients with active psoriatic arthritis.

Methods: In this investigator-initiated, randomised, multicentre, placebo-controlled, phase 3b non-inferiority trial done in 22 centres in Germany, patients with active psoriatic arthritis received open-label ustekinumab and were randomly assigned (1:1) to masked concomitant therapy with placebo or methotrexate (ongoing or new).

Differences in treatment response between female and male psoriatic arthritis patients during IL-12/23 therapy with or without methotrexate: post hoc analysis of results from the randomised MUST trial.

Background: The influence of sex on treatment outcomes during interleukin-12/23 therapy in patients with psoriatic arthritis (PsA) has not been explored.

Objective: To conduct exploratory post hoc analyses of sex-stratified data from the MUST trial, an investigator-initiated, multicentre, phase 3b study in which patients with active PsA initiating treatment with open-label ustekinumab were randomised to treatment with placebo or methotrexate (MTX).

Methods: We evaluated baseline characteristics, key treatment outcomes and adverse events stratified by sex, with a focus on outcomes that did not include erythrocyte sedimentation rate (ESR) as a component due to the known elevation of ESR in females.

Real-world effectiveness of golimumab in the treatment of patients with active rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis who failed initial TNF-α inhibitor therapy: a pooled analysis of European prospective observational studie.

Objectives: Rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) patients often experience secondary non-response to a first-line tumour necrosis factor alpha inhibitor (TNFαi). This pooled analysis of six observational studies in Europe (GO-BEYOND program) provides an estimate of second-line golimumab (GLM) effectiveness for these rheumatic diseases.

Methods: The GO-BEYOND studies included common disease-specific endpoints allowing for a pooled analysis.

Real-World Effectiveness and Safety of SDZ ETN, an Etanercept Biosimilar, in Patients with Rheumatic Diseases: Final Results from Multi-Country COMPACT Study.

Introduction: COMPACT, a non-interventional study, evaluated the persistence, effectiveness, safety and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA), axial-spondyloarthritis (axSpA) or psoriatic arthritis (PsA) treated with SDZ ETN (etanercept [ETN] biosimilar) in Europe and Canada.

Methods: Patients (aged ≥ 18 years) who have been treated with SDZ ETN were categorised on the basis of prior treatment status (groups A-D): patients in clinical remission or with low disease activity under treatment with reference ETN or biosimilar ETN and switched to SDZ ETN; patients who received non-ETN targeted therapies and switched to SDZ ETN; biologic-naïve patients who started SDZ ETN after conventional therapy failure; or disease-modifying anti-rheumatic drug (DMARD)-naïve patients with RA considered suitable for treatment initiation with a biologic and started on treatment with SDZ ETN. The primary endpoint was drug persistence, defined as time from study enrolment until discontinuation of SDZ ETN treatment.

Effectiveness of Different Rituximab Doses Combined with Leflunomide in the Treatment or Retreatment of Rheumatoid Arthritis: Part 2 of a Randomized, Placebo-Controlled, Investigator-Initiated Clinical Trial (AMARA).

Background: The optimal dose of rituximab in combination with leflunomide in patients with rheumatoid arthritis (RA) is not known.

Methods: In Part 1 (previously reported) of the investigator-initiated AMARA study (EudraCT 2009-015950-39; ClinicalTrials.gov NCT01244958), improvements at week (W)24 were observed in patients randomized to rituximab + leflunomide compared with placebo + leflunomide.

Long-Term Efficacy and Safety of Risankizumab in Patients with Active Psoriatic Arthritis: Results from a 76-Week Phase 2 Randomized Trial.

Introduction: The objective of this work was to assess the efficacy and safety of risankizumab in psoriatic arthritis (PsA) over 76 weeks.

Methods: In this double-blind, dose-ranging phase 2 study, adults with active PsA were randomized 2:2:2:1:2 to risankizumab 150 mg at weeks 0, 4, 8, 12, and 16 (arm 1), 150 mg at weeks 0, 4, and 16 (arm 2), 150 mg at weeks 0 and 12 (arm 3), 75 mg at week 0 (arm 4), or placebo (arm 5). Patients completing week 24 could receive risankizumab 150 mg in a 52-week open-label extension study.

The Sensitivity to Change of the ASAS Health Index in an Observational Real-Life Cohort Study.

Objective: The Assessment of Spondyloarthritis international Society Health Index (ASAS HI) measures global functioning and health in patients with axial spondyloarthritis (axSpA) covering domains of physical, emotional, and social functioning. The main aim of this study was to investigate the sensitivity to change of ASAS HI in comparison with established variables of disease activity, function, and mental health.

Methods: Patients with axSpA from the disease register RABBIT-SpA with follow-up time of at least 12 months and available ASAS HI questionnaires were included.

The safety and effectiveness of tocilizumab in elderly patients with rheumatoid arthritis and in patients with comorbidities associated with age.

Objectives: To examine the safety and effectiveness of long-term tocilizumab treatment in elderly patients with rheumatoid arthritis (RA) and patients with age-associated comorbidities.

Methods: ICHIBAN (NCT01194401) was a prospective, non-interventional study that observed adult patients with active moderate-to-severe RA in German rheumatology clinics and practices for up to two years. Patients were to be treated according to the tocilizumab label.

Characterisation of depressive symptoms in rheumatoid arthritis patients treated with tocilizumab during routine daily care.

Objectives: To assess whether tocilizumab treatment is associated with changes in depression symptoms in patients with rheumatoid arthritis (RA) during routine daily care.

Methods: We retrospectively analysed data from a German non-interventional study (ARATA) of adult, tocilizumab-naïve RA patients who initiated subcutaneous tocilizumab and were followed for 52 weeks. The Beck Depression Inventory II (BDI-II) was used to assess symptoms of depression and create baseline subgroups of no (BDI-II<14), mild (14-19), moderate (20-28), and severe (≥29) depression.

Rituximab plus leflunomide in rheumatoid arthritis: a randomized, placebo-controlled, investigator-initiated clinical trial (AMARA study).

Objective: To investigate the efficacy and safety of rituximab + LEF in patients with RA.

Methods: In this investigator-initiated, randomized, double-blind, placebo-controlled phase 3 trial, patients with an inadequate response to LEF who had failed one or more DMARD were randomly assigned 2:1 to i.v.

ICHIBAN, a non-interventional study evaluating tocilizumab long-term effectiveness and safety in patients with active rheumatoid arthritis.

Objectives: We aimed to measure long-term effectiveness and safety of tocilizumab in patients with rheumatoid arthritis in daily German practice.

Methods: ICHIBAN was a prospective, multi-centre, non-interventional study (ML22928) that enrolled adult patients with active moderate to severe rheumatoid arthritis. Patients were to be treated according to tocilizumab label and observed for up to two years.

Long-term safety, immunogenicity and efficacy comparing FKB327 with the adalimumab reference product in patients with active rheumatoid arthritis: data from randomised double-blind and open-label extension studies.

Background/objective: FKB327 is a biosimilar of the antitumour necrosis factor adalimumab reference product (RP). A randomised, double-blind (DB) phase 3 study compared the efficacy of FKB327 with the RP in patients with active rheumatoid arthritis (RA) inadequately controlled with methotrexate (MTX). A subsequent randomised open-label extension (OLE) study with treatment switching assessed long-term safety, efficacy, pharmacokinetics and immunogenicity of FKB327 compared with the RP.

FKB327, an adalimumab biosimilar, versus the reference product: results of a randomized, Phase III, double-blind study, and its open-label extension.

Objective: To compare the efficacy, serum drug concentrations, immunogenicity, and safety of FKB327 with the adalimumab reference product (RP) in combination with methotrexate in patients with moderate-to-severe, active rheumatoid arthritis (RA).

Methods: Patients were randomized 1:1 in a double-blind study (NCT02260791), received 40 mg of FKB327 or RP by subcutaneous injection every other week for 24 weeks (Period I), then re-randomized 2:1, remaining on the same study drug or switching to the other up to week 54 in an open-label extension (Period II, NCT02405780). Efficacy was evaluated using American College of Rheumatology (ACR20) response rate difference at week 24 with equivalence margins of ± 13% and - 12% to + 15% using 95% and 90% confidence intervals (CIs), respectively.

[Rheumatism and gastroenterology].

Background: Gastroenterological and rheumatological diseases often have a systemic character, with disease manifestations beyond the area affected by the disease. Common disease-relevant pathophysiological pathways, e.g.

Early and late responses in patients with rheumatoid arthritis who were conventional synthetic disease-modifying anti-rheumatic drug inadequate responders and were treated with tocilizumab or switched to rituximab: an open-label phase 3 trial (MIRAI).

Objectives: To evaluate early and late responses in biological-naïve patients with rheumatoid arthritis (RA) initiating tocilizumab and early tocilizumab non-responders who switched to rituximab.

Methods: In this open-label, non-randomised phase 3 study, RA patients with inadequate response to conventional synthetic DMARDs received tocilizumab 8 mg/kg intravenously at study begin and weeks 4, 8 and 12. After evaluation at week 16, early responders (Disease Activity Score based on 28 joints-erythrocyte sedimentation rate [DAS28-ESR] <2.

Effects of BI 655064, an antagonistic anti-CD40 antibody, on clinical and biomarker variables in patients with active rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase IIa study.

Objective: To evaluate the safety, efficacy and therapeutic mechanism of BI 655064, an antagonistic anti-CD40 monoclonal antibody, in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX-IR).

Methods: In total, 67 patients were randomised to receive weekly subcutaneous doses of 120 mg BI 655064 (n=44) or placebo (n=23) for 12 weeks. The primary endpoint was the proportion of patients who achieved 20% improvement in American College of Rheumatology criteria (ACR20) at week 12.

Repeatability and response to therapy of dynamic contrast-enhanced magnetic resonance imaging biomarkers in rheumatoid arthritis in a large multicentre trial setting.

Objectives: To determine the repeatability and response to therapy of dynamic contrast-enhanced (DCE) MRI biomarkers of synovitis in the hand and wrist of rheumatoid arthritis (RA) patients, and in particular the performance of the transfer constant K , in a multicentre trial setting.

Methods: DCE-MRI and RA MRI scoring (RAMRIS) were performed with meticulous standardisation at baseline and 6 and 24 weeks in a substudy of fostamatinib monotherapy in reducing synovitis compared with placebo or adalimumab. Analysis employed statistical shape modelling to avoid biased regions-of-interest, kinetic modelling and heuristic analyses.

Long-term effects of secukinumab on MRI findings in relation to clinical efficacy in subjects with active ankylosing spondylitis: an observational study.

Introduction: A 28-week study suggested efficacy of the anti-interleukin-17A monoclonal antibody secukinumab in active ankylosing spondylitis (AS). MRI-assessed inflammation was reduced at weeks 6, 28.

Objective: To analyse the longer-term effects of secukinumab on MRI inflammatory and non-inflammatory spinal lesions in relation to its clinical efficacy in subjects with active AS.

Infliximab efficacy in rheumatoid arthritis after an inadequate response to etanercept or adalimumab: results of a target-driven active switch study.

Objective: Evaluate efficacy of infliximab with response-driven dosing in patients with active RA.

Research Design And Methods: Patients (n = 203) with active RA despite methotrexate + etanercept/adalimumab, participated in this active-infliximab-switch study. Infliximab 3 mg/kg was infused at Weeks 0, 2, 6, 14, and 22 with escalation to 5 or 7 mg/kg depending on EULAR response at Weeks 14 and 22.

One-year efficacy and safety results of secukinumab in patients with rheumatoid arthritis: phase II, dose-finding, double-blind, randomized, placebo-controlled study.

Objective: To evaluate the longer-term safety and efficacy of secukinumab, a fully human monoclonal antiinterleukin-17A antibody, in patients with rheumatoid arthritis.

Methods: In this 52-week, double-blind, placebo-controlled (up to Week 20) study (NCT00928512), patients responding inadequately to disease-modifying antirheumatic drugs (DMARD) or biologics were randomized to receive monthly subcutaneous injections of secukinumab (25, 75, 150, or 300 mg), or placebo. The efficacy and safety results up to Week 20 have been reported previously.

Celecoxib and Diclofenac Plus Omeprazole are Similarly Effective in the Treatment of Arthritis in Patients at High GI Risk in the CONDOR Trial.

Objective: Compare effectiveness of celecoxib versus diclofenac plus omeprazole in improving arthritis signs and symptoms in patients at high gastrointestinal (GI) risk who were enrolled in the CONDOR (Celecoxib vs Omeprazole and Diclofenac in Patients With Osteoarthritis and Rheumatoid Arthritis) trial.

Methods: CONDOR was a 6-month, prospective, double-blind, triple-dummy, parallel-group, randomized, multicenter trial comparing celecoxib 200 mg twice daily versus diclofenac slow release (SR) 75 mg twice daily plus omeprazole 20 mg daily. Patients were Helicobacter pylori negative, had osteoarthritis (OA) or rheumatoid arthritis (RA), were aged ≥60 years, were with or without a history of gastroduodenal ulceration, or were ≥18 years with previous gastroduodenal ulceration.

Evaluation of the novel ultrasound score for large joints in psoriatic arthritis and ankylosing spondylitis: six month experience in daily clinical practice.

Background: To evaluate the utility of the recently introduced SOLAR score (sonography of large joints in Rheumatology), which has been validated in RA patients, in a cohort of patients with Psoriatic Arthritis (PsA) and Ankylosing Spondylitis (AS) presenting with involvement of large peripheral joints.

Methods: The recently established SOLAR score has been designed to determine the degree of inflammation in the shoulder, the elbow, the hip and the knee joint in patients suffering from RA. Since large joints are frequently involved in PsA and AS, synovitis and synovial vascularity were scored semiquantitatively (grade 0-3) by grey scale (GSUS) and power Doppler ultrasound (PDUS) utilizing the validated scoring system.