Impact of immunogenicity on efficacy and tolerability of tumour necrosis factor inhibitors: pooled analysis of biosimilar studies in rheumatoid arthritis
Language English Country Great Britain, England Media print-electronic
Document type Journal Article
- MeSH
- Adalimumab adverse effects therapeutic use MeSH
- Antirheumatic Agents adverse effects therapeutic use MeSH
- Biosimilar Pharmaceuticals adverse effects therapeutic use MeSH
- Adult MeSH
- Etanercept adverse effects therapeutic use MeSH
- Infliximab adverse effects therapeutic use MeSH
- Tumor Necrosis Factor Inhibitors adverse effects therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Antibodies MeSH
- Arthritis, Rheumatoid drug therapy MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Adalimumab MeSH
- Antirheumatic Agents MeSH
- Biosimilar Pharmaceuticals MeSH
- Etanercept MeSH
- Infliximab MeSH
- Tumor Necrosis Factor Inhibitors MeSH
- Antibodies MeSH
Objective: SB4, SB2, and SB5 are biosimilars of etanercept (ETN), infliximab (INF), and adalimumab (ADA), respectively. This pooled analysis evaluated the immunogenicity of these treatments across three phase III randomized controlled trials of patients with rheumatoid arthritis (RA). Methods: Patients had to have at least one anti-drug antibody (ADAb) assessment up to the time of the primary endpoint from each study (week 24 in SB4 and SB5 studies; week 30 in SB2 study). The effect of ADAbs on American College of Rheumatology 20% (ACR20) response and the incidences of injection-site reactions (ISRs)/infusion-related reactions (IRRs) were evaluated. Results: The study included 1709 patients. The cumulative incidences of ADAbs were 30.3% in the all-treatments-combined group, 29.1% in the biosimilars combined group, and 31.5% in the reference products combined group. ACR20 response rates were significantly lower in ADAb-positive patients in the all-treatments-combined [odds ratio (95% confidence interval) 1.77 (1.37, 2.27), p < 0.0001], biosimilars combined [2.24 (1.53, 3.30), p < 0.0001], and reference products combined [1.49 (1.06, 2.09), p = 0.0225] groups. ADAb-positive patients also had a higher likelihood of developing ISRs/IRRs in the all-treatments-combined group [0.56 (0.31, 1.01), p = 0.0550], predominantly due to the results observed with SB2 + INF combined rather than with SB4 + ETN or SB5 + ADA combined. Conclusion: In this pooled analysis, ADAbs were associated with reduced efficacy in patients with RA treated with biosimilars (SB4, SB2, and SB5) or their reference products (ETN, INF, and ADA). ADAbs were associated with an increased incidence of ISRs/IRRs in those treated with SB2 + INF. Clinical trial registration numbers: NCT01936181 (SB2 study), NCT01895309 (SB4 study), and NCT02167139 (SB5 study).
Department of Rheumatology Ajou University School of Medicine Suwon Republic of Korea
Department of Rheumatology Institute of Rheumatology Prague Czech Republic
Division of Rheumatology Department of Medicine Medical University of Vienna Vienna Austria
Division of Rheumatology Immunology and Allergy Brigham and Women's Hospital Boston MA USA
Division of Rheumatology Mount Sinai Hospital University of Toronto Toronto ON Canada
NIHR Leeds Musculoskeletal Biomedical Research Unit Leeds Teaching Hospitals NHS Trust Leeds UK
References provided by Crossref.org
ClinicalTrials.gov
NCT01895309, NCT02167139
