Lead Investigator: Carl Turesson, Lund University
Title of Proposal Research: Efficacy and safety of tumor necrosis factor inhibitors (TNFi) in seronegative rheumatoid arthritis patients who are inadequate responders to conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs). A systematic literature review with meta-analysis.
Vivli Data Request: 7826
Funding Source: None
Potential Conflicts of Interest: Consulting fees from Roche, speaker fees from Abbvie, Bristol Myers-Squibb, Nordic Drugs, Pfizer and Roche, and an unrestricted research grant from Bristol Myers-Squibb.
The present study is not funded by the above reported pharmaceutical companies.
Summary of the Proposed Research:
Rheumatoid arthritis (RA) is a chronic autoimmune disease that is characterised by circulating autoantibodies, rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). These are antibodies that target proteins belonging to the patient and are thought to be involved in the disease mechanism. However, about 20% of patients with RA do not have RF and ACPA in their blood. Therefore, RA is classified as seropositive or seronegative according to the presence or absence of RF and ACPA, respectively. Seropositive and seronegative RA are not exactly the same disease: for example, seropositive RA is more severe than seronegative RA. Tumor necrosis factor (TNF) is a body protein involved in the inflammatory process of RA. TNF inhibitors (TNFi) are drugs that target TNF and are an established treatment for RA, since randomised clinical trials (RCTs) showed their efficacy and safety in patients with this condition. However, the great majority of patients that are included in RCTs have seropositive RA and therefore we do not know whether TNFi are effective in seronegative RA as well. We would like to fill this knowledge gap by performing a systematic literature review with meta-analysis of RCTs, since this is the best way to assess such clinical question. We have already performed a literature search showing that there are no RCTs specifically on seronegative RA. We will proceed by requesting data of seronegative patients from the existing RCTs on RA. Afterwards, we will pool the data in a meta-analysis to assess RA related clinical outcomes. The generated evidence will be summarised and qualitatively judged according to Cochrane methodology.
Requested Studies:
A Randomized, Double-Blind, Placebo- and Active-Controlled, Phase 3 Study Evaluating the Efficacy and Safety of Baricitinib in Patients With Moderately to Severely Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Methotrexate Therapy
Data Contributor: Lilly
Study ID: NCT01710358
Sponsor ID: 13978
A Study of Adalimumab in Adult Japanese Subjects With Rheumatoid Arthritis
Data Contributor: AbbVie
Study ID: NCT00647491
Sponsor ID: M02-575
A Phase III Multicentre, Double Blind, Placebo-controlled, Parallel Group 52-week Study to Assess the Efficacy and Safety of 2 Dose Regimens of Lyophilised CDP870 as Additional Medication to Methotrexate in the Treatment of Signs and Symptoms and Preventing Structural Damage in Patients With Active Rheumatoid Arthritis Who Have an Incomplete Response to Methotrexate
Data Contributor: UCB
Study ID: NCT00152386
Sponsor ID: C87027
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab in Rheumatoid Arthritis Patients Currently Receiving Treatment With Methotrexate
Data Contributor: AbbVie
Study ID: NCT00195702
Sponsor ID: DE019
A Multi-center Randomized, Phase 2/3, Double-blind, Parallel-group, Placebo-controlled Study to Assess the Safety and Efficacy of Adalimumab Administered as Subcutaneous Injections in Adult Chinese Rheumatoid Arthritis Subjects Treated With Methotrexate
Data Contributor: AbbVie
Study ID: NCT00538902
Sponsor ID: M04-705
A Placebo-Controlled, Double-Blinded, Randomized Clinical Trial of Anti-TNF Chimeric Monoclonal Antibody (cA2) in Patients With Active Rheumatoid Arthritis Despite Methotrexate Treatment
Data Contributor: Johnson & Johnson
Study ID: NCT00269867
Sponsor ID: CR006259