Josef Sebastian Smolen

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. The Oral Rheumatoid Arthritis triaL (ORAL) Strategy aimed to assess the comparative efficacy of tofacitinib monotherapy, tofacitinib plus methotrexate, and adalimumab plus methotrexate for the treatment of rheumatoid arthritis in patients with a previous inadequate response to methotrexate.

METHODS: ORAL Strategy was a 1 year, double-blind, phase 3b/4, head-to-head, non-inferiority, ...

BACKGROUND: Upadacitinib, an oral Janus kinase (JAK)1-selective inhibitor, showed efficacy in combination with stable background conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in patients with rheumatoid arthritis who had an inadequate response to DMARDs. We aimed to evaluate the safety and efficacy of upadacitinib monotherapy after switching from methotrexate versus continuing methotrexate in patients with inadequate response to methotrexate.

METHODS: ...

BACKGROUND: Clinical remission and low disease activity are essential treatment targets in patients with rheumatoid arthritis. Although moderately active rheumatoid arthritis is common, treatment effects in moderate disease have not been well studied. Additionally, optimum use of biologics needs further investigation, including the use of induction, maintenance, and withdrawal treatment strategies. The aim of the PRESERVE trial was to assess whether low disease activity would be ...

BACKGROUND: Biological agents offer good control of rheumatoid arthritis, but the long-term benefits of achieving low disease activity with a biological agent plus methotrexate or methotrexate alone are unclear. The OPTIMA trial assessed different treatment adjustment strategies in patients with early rheumatoid arthritis attaining (or not) stable low disease activity with adalimumab plus methotrexate or methotrexate monotherapy.

METHODS: This trial was done at 161 sites worldwide. ...

OBJECTIVE: To investigate the efficacy of single and combined blockade of tumor necrosis factor (TNF), interleukin-1 (IL-1), and RANKL pathways on synovial inflammation, bone erosion, and cartilage destruction in a TNF-driven arthritis model.

METHODS: Human TNF-transgenic (hTNFtg) mice were treated with anti-TNF (infliximab), IL-1 receptor antagonist (IL-1Ra; anakinra), or osteoprotegerin (OPG; an OPG-Fc fusion protein), either alone or in combinations of 2 agents or all 3 agents. ...

Local bone erosion and systemic bone loss are hallmarks of rheumatoid arthritis and cause progressive disability. Tumor necrosis factor (TNF) is a key mediator of arthritis and acts catabolically on bone by stimulating bone resorption and inhibiting bone formation. We hypothesized that the concerted action of anti-TNF, which reduces inflammation and parathyroid hormone (PTH), which stimulates bone formation, or osteoprotegerin (OPG), which blocks bone resorption and could lead to repair ...

BACKGROUND: Tumour necrosis factor alpha (TNFalpha) inhibitors are frequently used to treat rheumatoid arthritis, but whether use of a different TNFalpha inhibitor can improve patient response is unknown. We assess the efficacy and safety of the TNFalpha inhibitor golimumab in patients with active rheumatoid arthritis who had previously received one or more TNFalpha inhibitors.

METHODS: 461 patients with active rheumatoid arthritis from 82 sites in 10 countries were randomly allocated by ...

BACKGROUND: Not all patients with rheumatoid arthritis can tolerate or respond to methotrexate, a standard treatment for this disease. There is evidence that antitumour necrosis factor alpha (TNFalpha) is efficacious in relief of signs and symptoms. We therefore investigated whether infliximab, a chimeric human-mouse anti-TNFalpha monoclonal antibody would provide additional clinical benefit to patients who had active rheumatoid arthritis despite receiving methotrexate.

METHODS: In an ...

OBJECTIVE: To evaluate the efficacy and safety of repeated administration of infliximab plus methotrexate (MTX) over a 2-year period in patients with rheumatoid arthritis (RA) who previously experienced an incomplete response to MTX.

METHODS: Four hundred twenty-eight patients were randomly assigned to receive MTX plus placebo or infliximab at a dose of 3 or 10 mg/kg plus MTX for 54 weeks, with an additional year of followup. The protocol was later amended to allow for continued ...

OBJECTIVES: To compare the efficacy, safety, immunogenicity and pharmacokinetics (PK) of SB2 to the infliximab reference product (INF) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate therapy.

METHODS: This is a phase III, randomised, double-blind, multinational, multicentre parallel group study. Patients with moderate to severe RA despite methotrexate therapy were randomised in a 1:1 ratio to receive either SB2 or INF of 3 mg/kg. The primary end point ...

BACKGROUND: To date, head-to-head trials comparing the efficacy and safety of biological disease-modifying antirheumatic drugs within the same class, including TNF inhibitors, in patients with active rheumatoid arthritis despite methotrexate therapy are lacking. We aimed to compare the efficacy and safety of two different TNF inhibitors and to assess the efficacy and safety of switching to the other TNF inhibitor without a washout period after insufficient primary response to the first ...

OBJECTIVE: To validate and compare the definition of the Disease Activity Score 28 based on C-reactive protein (DAS28 (CRP)) to the definition based on erythrocyte sedimentation rate (ESR).

METHODS: Data were analysed from two randomised, double-blind, placebo-controlled trials of abatacept of 6-month and 12-month duration in patients with rheumatoid arthritis. European League Against Rheumatism (EULAR) response criteria and the proportion of patients in remission (DAS28 <2.6) based on ...

OBJECTIVE: To assess the relationship between inflammation and joint destruction in rheumatoid arthritis (RA) patients who have not responded clinically to treatment.

METHODS: Changes from baseline to week 54 in clinical variables and measures of radiographic progression were compared between patients who received infliximab (3 mg/kg or 10 mg/kg every 4 or 8 weeks) plus methotrexate (MTX) and those who received MTX plus placebo in the Anti-Tumor Necrosis Factor Trial in RA with ...

OBJECTIVE: To identify disease characteristics leading to progression of joint damage in patients with early rheumatoid arthritis (RA) treated with methotrexate (MTX) versus those treated with infliximab plus MTX.

METHODS: Patients who had not previously been treated with MTX with active RA were randomly assigned to receive escalating doses of MTX up to 20 mg/week plus placebo or infliximab at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46. Radiographic joint damage was ...

BACKGROUND: Interleukin 6 is involved in the pathogenesis of rheumatoid arthritis via its broad effects on immune and inflammatory responses. Our aim was to assess the therapeutic effects of blocking interleukin 6 by inhibition of the interleukin-6 receptor with tocilizumab in patients with rheumatoid arthritis.

METHODS: In this double-blind, randomised, placebo-controlled, parallel group phase III study, 623 patients with moderate to severe active rheumatoid arthritis were randomly ...