Effectiveness of Certolizumab-Pegol in Rheumatoid Arthritis, Spondyloarthritis, and Psoriatic Arthritis Based on the BIOPURE Registry: Can Early Response Predict Late Outcomes?
- 68 Downloads
Identification of predictors of clinical response to certolizumab-pegol (certolizumab) may aid the decision-making process for treating patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA).
The aim of our study was to evaluate the effectiveness of certolizumab and identify any predictors of favorable outcome in patients with RA, PsA, or SpA.
We studied 355 RA, SpA, and PsA patients starting treatment with certolizumab. Endpoints of the study were drug survival and identification of predictors of clinical outcome. Drug retention was analyzed via the Kaplan–Meier method, and hazard ratios (HRs) were estimated using Cox regression models.
Of 355 certolizumab initiators, 178 had RA, 94 had PsA, and 83 had SpA. Biologic-naïve RA patients had significantly higher survival rates (73.3%) than switchers taking certolizumab as a second-line (49.0%) or third- or next-line biologic agent (51.2%; p = 0.0001). Instead, PsA and SpA patients showed similar drug retention rates regardless of the line of treatment. A significant clinical improvement from baseline was seen at 3 months for RA (28 joint-Disease Activity Score [DAS28]; p = 0.001), PsA (Disease Activity Index for PsA [DAPSA]; p = 0.001), and SpA (Bath Ankylosing Disease Index; p = 0.01). Biologic-naïve patients had the lowest HR (0.31; p = 0.001) of discontinuing certolizumab for RA, and the highest HR (7.94; p = 0.01) of achieving minimal disease activity (MDA) for PsA. For PsA, a predictor of late MDA was the achievement of low/remission DAPSA at 3 months, and 3-month low/remission DAS28 predicted late remission for RA.
Our study revealed that the best predictor of certolizumab effectiveness in unselected patients with RA, PsA, or SpA was a biologic-naïve status and achievement of an early response within 3 months.
The authors are thankful to Massimiliano Dellisanti Fabiano Vilardi, Electronic Engineer, Ph.D., for his support in managing the BIOPURE registry and extracting the data for this study. The corresponding author declares that all authors approved all the submitted material and actively contributed to the study.
Compliance with Ethical Standards
Conflict of interest
Florenzo Iannone has received consultancy fees and/or speaker honoraria from Pfizer, AbbVie, MSD, BMS, Novartis, Lilly, and UCB outside this work. Angelo Semeraro has received speaker honoraria from Sanofi, Roche, AbbVie, BMS, MSD, and Novartis. Giorgio Carlino has received consultancy fees from Pfizer, Janssen, AbbVie, MSD, and BMS. Leonardo Santo has received consultancy fees and/or speaker honoraria from AbbVie, MSD, Novartis, and UCB outside this work. Romano Bucci has received consultancy fees and/or speaker honoraria from Pfizer, Sanofi, MSD, and BMS. Nicola Maruotti has received speaker honoraria from Pfizer outside this work. Carmelo Zuccaro has received consultancy fees and/or speaker honoraria from MSD, AbbVie, Novartis, Pfizer, and Janssen outside this work. Paola Chiara Falappone has received consultancy fees and/or speaker honoraria from Amgen, Abbott, MSD, and BMS outside this work. Francesco Paolo Cantatore has received consultancy fees and/or speaker honoraria from Pfizer and Roche outside this work. Giovanni Lapadula has received consultancy fees and/or speaker honoraria from Pfizer, AbbVie, MSD, BMS, and UCB outside this work. Laura Quarta, Daniela Mazzotta, Antonio Marsico, and Maurizio Muratore have no disclosures to declare.
This study obtained the approval of the local ethics committees (Ethics Review Board of Policlinico of Bari (firstname.lastname@example.org), protocol number 5277).
Patients gave their written informed consent to take part in this study and to use their data for publication, with explicit protection of identification. The study was conducted in compliance with the Declaration of Helsinki.
The BIOPURE registry has received unrestricted grants from Amgen, Roche, MSD, and UCB. UCB had no role in the study design or interpretation of the data. The submission of this article was unrelated to any approval from UCB.
All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version for publication. Dr. Iannone had full access to all of the data in this study and takes responsibility for the integrity of the data and accuracy of the data analysis. Study conception and design: FI, AS, and GL. Acquisition of data: LS, RB, AS, LQ, NM, AM, GC, DM, CZ, PCF, FPC, MM, and GL. Analysis of data: FI and AS. Interpretation of data: All authors.
- 6.Thomas K, Flouri I, Repa A, Fragiadaki K, Sfikakis PP, Koutsianas C, et al. High 3-year golimumab survival in patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis: real world data from 328 patients. Clin Exp Rheumatol. 2018;36:254–62.Google Scholar
- 7.Landewé R, Braun J, Deodhar A, Dougados M, Maksymowych WP, Mease PJ, et al. Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled Phase 3 study. Ann Rheum Dis. 2014;73:39–47.CrossRefGoogle Scholar
- 8.Mease PJ, Fleischmann R, Deodhar AA, Wollenhaupt J, Khraishi M, Kielar D, et al. Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis: 24-week results of a phase 3 double-blind randomised placebo-controlled study (RAPID-PsA). Ann Rheum Dis. 2014;73:48–55.CrossRefGoogle Scholar
- 11.Iannone F, Carlino G, Marchesoni A, Sarzi-Puttini P, Gorla R, Lapadula G, GISEA (Gruppo Italiano di Studio sulle Early Arthritides). Early clinical response predicts low disease activity at one year in rheumatoid arthritis patients on treatment with certolizumab in real-life settings. An appraisal of the Italian registry GISEA. Jt Bone Spine. 2016;83:721–5.CrossRefGoogle Scholar
- 18.van der Heijde D, Deodhar A, Fleischmann R, Mease PJ, Rudwaleit M, Nurminen T, et al. Early disease activity or clinical response as predictors of long-term outcomes with certolizumab pegol in axial spondyloarthritis or psoriatic arthritis. Arthritis Care Res (Hoboken). 2017;69:1030–9.CrossRefGoogle Scholar
- 21.Torrente-Segarra V, Bergstra SA, Salomon-Escoto K, Da Silva J, Veale DJ, Al-Emadi S, et al. Is current smoking status and its relationship to anti-cyclic citrullinated peptide antibodies a predictor of worse response to biological therapies in rheumatoid arthritis patients? Scand J Rheumatol. 2018;47(5):360–3.CrossRefGoogle Scholar