Head-to-head comparison of certolizumab pegol versus adalimumab in rheumatoid arthritis: 2-year efficacy and safety results from the randomised EXXELERATE study

Smolen, Josef S.; Burmester, Gerd‐Rüdiger; Combe, Bernard; Curtis, Jeffrey R.; Hall, Stephen; Haraoui, Boulos; Vollenhoven, Ronald van; Cioffi, Christopher; Ecoffet, C.; Gervitz, Leon; Ionescu, Lucian; Peterson, Luke; Fleischmann, Roy

doi:10.1016/s0140-6736(16)31651-8

Cited by 151 publications

(119 citation statements)

References 27 publications

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“…Through week 12, ~40% of patients receiving upadacitinib achieved CDAI‐defined LDA and 29% achieved a DAS28‐CRP score of <2.6. The proportions of patients who achieved LDA and remission by a variety of composite measures were significantly higher in the upadacitinib group than in the adalimumab group, with differences observed as early as week 8 and persisting through week 26; this is the first trial demonstrating superiority of a treatment to standard‐of‐care adalimumab in combination with MTX, based on consistent achievement of remission outcomes .…”

Section: Discussionmentioning

confidence: 80%

Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double‐Blind, Randomized Controlled Trial

Fleischmann

Pangan

Song

et al. 2019

Arthritis & Rheumatology

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325

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Objective To evaluate the efficacy, including capacity for inhibition of radiographic progression, and safety of upadacitinib, a JAK1‐selective inhibitor, as compared to placebo or adalimumab in patients with rheumatoid arthritis (RA) who have experienced an inadequate response to methotrexate (MTX). Methods In total, 1,629 RA patients with an inadequate response to MTX were randomized (2:2:1) to receive upadacitinib (15 mg once daily), placebo, or adalimumab (40 mg every other week) while continuing to take a stable background dose of MTX. The primary end points were achievement of an American College of Rheumatology 20% (ACR20) improvement response and a Disease Activity Score in 28 joints using C‐reactive protein level (DAS28‐CRP) of <2.6 in the upadacitinib group compared to the placebo group at week 12; inhibition of radiographic progression was evaluated at week 26. The study was also designed and powered to test for the noninferiority and superiority of upadacitinib compared to adalimumab, as measured both clinically and functionally. Results At week 12, both primary end points were met in patients receiving upadacitinib compared to those receiving placebo (P ≤ 0.001). An ACR20 improvement response was achieved by 71% of patients in the upadacitinib group compared to 36% in the placebo group, and a DAS28‐CRP score of <2.6 was observed in 29% of patients receiving upadacitinib compared to 6% of patients receiving placebo. Upadacitinib was superior to adalimumab based on the ACR50 response rate, achievement of a DAS28‐CRP score of ≤3.2, change in pain severity score, and change in the Health Assessment Questionnaire disability index. At week 26, more patients receiving upadacitinib than those receiving placebo or adalimumab achieved low disease activity or remission (P ≤ 0.001). Radiographic progression was significantly inhibited in patients receiving upadacitinib and was observed in fewer upadacitinib‐treated patients than placebo‐treated patients (P ≤ 0.001). Up to week 26, adverse events (AEs), including serious infections, were comparable between the upadacitinib and adalimumab groups. The proportions of patients with serious AEs and AEs leading to discontinuation were highest in the adalimumab group; the proportions of patients with herpes zoster and those with creatine phosphokinase (CPK) elevations were highest in the upadacitinib group. Three malignancies, 5 major adverse cardiovascular events, and 4 deaths were reported among the groups, but none occurred in patients receiving upadacitinib. Six venous thromboembolic events were reported (1 in the placebo group, 2 in the upadacitinib group, and 3 in the adalimumab group). Conclusion Upadacitinib was superior to placebo and adalimumab for improving signs, symptoms, and physical function in RA patients who were receiving background MTX. In addition, radiographic progression was significantly inhibited by upadacitinib as compared to placebo. The overall safety profile of upadacitinib was generally similar to that of adalimumab, except for higher rates ...

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Section: Discussionmentioning

confidence: 80%

Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double‐Blind, Randomized Controlled Trial

Fleischmann

Pangan

Song

et al. 2019

Arthritis & Rheumatology

Self Cite

325

338

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“…A similar recommendation was presented in 2013: ‘If a first bDMARD has failed, patients should be treated with another bDMARD; if a first TNF-inhibitor therapy has failed, patients may receive another TNF-inhibitor or a biological agent with another mode of action’. Indeed, in a trial published after the elaboration of these recommendations, even primary non-responders to a TNF-inhibitor were shown to have some response to another anti-TNF, making it difficult to draw different conclusions for subsequent therapy for primary compared with secondary failures to TNF-blockers 176. The addition in the first part (‘or tsDMARD’) was partly needed because tsDMARDs (Jak inhibition) are now included in the earlier recommendations 8 and 9; ‘first’ was deleted, because the Task Force did not decide to distinguish between failure of one or more bDMARDs.…”

Section: Resultsmentioning

confidence: 99%

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update

et al. 2017

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Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to—or adding—another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.

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“…It would seem unusual for drugs acting on the same pathway with similar efficacy to have such drastically different infection risks. In the EXXELERATE study, a direct head to head clinical trial of certolizumab pegol versus adalimumab the rate of serious infection was the same with both drugs at 3% though event numbers were small 15. The Cochrane review was a network meta-analysis using indirect comparisons between biologics to estimate the relative risk of infection.…”

Section: Discussionmentioning

confidence: 99%

Serious infection across biologic-treated patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

et al. 2018

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The rate of SI was lower with certolizumab pegol than etanercept in the primary analysis but the result was no longer significant in several sensitivity analyses performed suggesting residual confounding may account for the observed difference. From these results, it would be wrong to conclude that certolizumab pegol has a lower rate of SI than other biologics; however, the risk does not appear to be significantly higher as has previously been suggested.

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Head-to-head comparison of certolizumab pegol versus adalimumab in rheumatoid arthritis: 2-year efficacy and safety results from the randomised EXXELERATE study

Cited by 151 publications

References 27 publications

Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double‐Blind, Randomized Controlled Trial

Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double‐Blind, Randomized Controlled Trial

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update

Serious infection across biologic-treated patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

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