Impact of high rheumatoid factor levels on treatment outcomes with certolizumab pegol and adalimumab in patients with rheumatoid arthritis
Abstract Objectives To assess the impact of baseline RF level on drug concentrations and efficacy of certolizumab pegol [CZP; TNF inhibitor (TNFi) without a crystallizable fragment (Fc)] and adalimumab (ADA; Fc-containing TNFi) in patients with RA. Methods The phase 4 EXXELERATE study (NCT01500278) was a 104-week, randomized, single-blind (double-blind until week 12; investigator-blind thereafter), head-to-head study of CZP vs ADA in patients with RA. In this post hoc analysis, we report drug concentration and efficacy outcomes stratified by baseline RF quartile (≤Q3 or >Q3). Results Baseline data by RF quartiles were available for 453 CZP-randomized and 454 ADA-randomized patients (≤Q3: ≤204 IU/ml; >Q3: >204 IU/ml). From week 12, the area under the curve (AUC) of ADA concentration was lower in patients with RF >204 IU/ml vs patients with RF ≤204 IU/ml; the AUC of CZP concentration was similar in patients with RF ≤204 IU/ml and >204 IU/ml. For patients with RF ≤204 IU/ml, disease activity score (DAS28)-CRP was similar between CZP- and ADA-treated patients through week 104. For patients with RF >204 IU/ml, mean DAS28-CRP was lower in CZP- vs ADA-treated patients at week 104. The proportion of patients with RF >204 IU/ml achieving DAS28-CRP low disease activity at week 104 was greater in CZP- vs ADA-treated patients. Conclusion CZP was associated with maintained drug concentration and efficacy in patients with RA and high RF and may therefore be a more suitable therapeutic option than TNFis with an Fc fragment in these patients. Trial registration Clinicaltrials.gov, http://clinicaltrials.gov, NCT01500278
Authors
- Jeffrey R. Curtis (ORCID: https://orcid.org/0000-0002-8907-8976)
- Bernard Lauwerys (ORCID: https://orcid.org/0000-0003-3243-6151)
- Yoshiya Tanaka (ORCID: https://orcid.org/0000-0002-0807-7139)
- Motomu Hashimoto (ORCID: https://orcid.org/0000-0002-9241-060X)
- Michael E. Weinblatt (ORCID: https://orcid.org/0000-0001-5215-5512)
- Alejandro Balsa (ORCID: https://orcid.org/0000-0001-8070-7062)
- Baran Ufuktepe (ORCID: https://orcid.org/0000-0002-8909-4028)
- Nicola Tilt
- Ricardo Machado Xavier (ORCID: https://orcid.org/0000-0001-6570-4533)
- Tsutomu Takeuchi (ORCID: https://orcid.org/0000-0003-1111-8218)
- Ted R. Mikuls (ORCID: https://orcid.org/0000-0002-0897-2272)
- Josef S Smolen (ORCID: https://orcid.org/0000-0002-4302-8877)
- Peter C. Taylor (ORCID: https://orcid.org/0000-0001-7766-6167)
- Carlos Cara
Institutions
- Brigham and Women's Hospital (US)
- Universidade Federal do Rio Grande do Sul (BR)
- University of Alabama at Birmingham Hospital (US)
- Harvard University (US)
- University of Occupational and Environmental Health Japan (JP)
- Keio University (JP)
- Nuffield Orthopaedic Centre (GB)
- University of Alabama at Birmingham (US)
- University of Oxford (GB)
- Hospital de Clínicas de Porto Alegre (BR)
- UCB Pharma (Spain) (ES)
- Hospital La Paz Institute for Health Research (ES)
- UCB Pharma (United Kingdom) (GB)
- Universidad Metropolitana (VE)
- VA Nebraska Western Iowa Health Care System (US)
- Osaka Metropolitan University (JP)
- University of Nebraska Medical Center (US)
- Tokyo Metropolitan University (JP)
- Medical University of Vienna (AT)
- UCB Pharma (Belgium) (BE)
- Saitama Medical University (JP)
Publication Details
- Journal
- Lara D. Veeken
- Published
- 2024-09-02
- DOI
- https://doi.org/10.1093/rheumatology/keae435
- Citations
- 12
- Primary Topic
- Rheumatoid Arthritis Research and Therapies
- Type
- article
- Field-Weighted Citation Impact
- 5.64
Funders
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Sanofi
- Gilead Sciences
- Biogen
- Celgene
- Taiho Pharmaceutical
- Celltrion
- Horizon Therapeutics
- Eisai
- Astellas Pharma
- Nordic Pharma Group
- Genentech
- Samsung
- Merck Sharp and Dohme
- Pfizer Japan
- Chugai Pharmaceutical
- UCB Pharma
- Daiichi Sankyo Europe