Efficacy and safety of certolizumab pegol in a broad population of patients with active rheumatoid arthritis: results from the REALISTIC phase IIIb study

Weinblatt, Michael E.; Fleischmann, Roy; Huizinga, Tom W J; Emery, Paul; Pope, Janet; Massarotti, Elena; Vollenhoven, Ronald F. van; Wollenhaupt, J.; Bingham, Clifton O.; Duncan, Ben; Goel, Niti; Davies, O.; Dougados, Maxime

doi:10.1093/rheumatology/kes150

Cited by 113 publications

(78 citation statements)

References 16 publications

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“…Studies of biologics that target cytokines and cytokine receptors such as TNF-α [4][5][6][7][8] and IL-6 [9] have established a standard of RA therapy for patients with disease-modifying anti-rheumatic drug (DMARD)-resistant disease. These drugs have created new goals of disease remission from both clinical and radiological perspectives.…”

Section: Introductionmentioning

confidence: 99%

Levels of interleukin-1 beta can predict response to tocilizumab therapy in rheumatoid arthritis: the PETITE (predictors of effectiveness of tocilizumab therapy) study

et al. 2015

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Predicting the responses of patients with rheumatoid arthritis (RA) to tocilizumab is difficult, because inflammatory markers such as C-reactive protein rapidly normalize regardless of clinical efficacy. We aimed to identify factors that could predict response to tocilizumab. Sixty-five patients completed 52 weeks of tocilizumab therapy. Serum fibrinogen, D-dimer and interleukin (IL)-1β levels were measured at baseline and after 4 weeks of therapy. Clinical responses to tocilizumab were assessed using disease activity score 28-erythrocyte sedimentation rate and the clinical disease activity index at baseline and after 52 weeks of therapy (UMIN Clinical Trials Registry No. UMIN000002246). Mean age was 60.5 years (range 22-85 years). Mean disease duration was 11.2 years (range 0-45 years). All patients had moderate-to-severe disease activity and were resistant to disease-modifying anti-rheumatic drugs and/or other biologics. Baseline IL-1β levels were significantly lower in responders than in non-responders (p = 0.045), but multiple logistic regression analysis found no significant difference (adjusted odds ratio 2.74; 95 % confidence interval 0.84-8.95; p = 0.096). Low D-dimer and IL-1β levels at 4 weeks predicted greater decrease in disease activity after 52 weeks of treatment (p = 0.005 and p < 0.001, respectively). Effects of tocilizumab at 52 weeks could be predicted from D-dimer and IL-1β levels after 4 weeks of tocilizumab treatment. These markers might be more useful than current inflammatory markers for early-stage prediction of response to tocilizumab in RA.

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Section: Introductionmentioning

confidence: 99%

Levels of interleukin-1 beta can predict response to tocilizumab therapy in rheumatoid arthritis: the PETITE (predictors of effectiveness of tocilizumab therapy) study

et al. 2015

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“…This evidence was based on six RCTs (REALISTIC, [24] DOSEFLEX, [25] PREDICT, [26] SWITCH, [27] J-RAPID [28] and HIKARI [29]). …”

Section: Clinical Evidence Provided By the Companymentioning

confidence: 99%

Certolizumab Pegol for Treating Rheumatoid Arthritis Following Inadequate Response to a TNF-α Inhibitor: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

et al. 2017

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As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (UCB Pharma) of certolizumab pegol (CZP;Cimzia®) to submit evidence of its clinical and cost-effectiveness for the treatment of rheumatoid arthritis (RA) following inadequate response to a tumour necrosis factor-alpha inhibitor (TNFi). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a detailed review of the evidence for the clinical and cost-effectiveness of the technology, based upon the company's submission to NICE. The clinical effectiveness evidence in the company's submission for CZP was based predominantly on six randomised controlled trials (RCTs) comparing the efficacy of CZP against placebo. The clinical-effectiveness review identified no head to head evidence on the efficacy of CZP against the comparators within the scope; therefore the company performed a network meta-analysis (NMA). The company's NMA concluded that CZP had a similar efficacy to that of its comparators. The company submitted a Markov model that assessed the incremental cost effectiveness of CZP versus comparator biologic disease-modifying antirheumatic drugs (bDMARDs) for the treatment of RA from the perspective of the National Health Service for three decision problems each of which followed an inadequate response to a TNFi. These were (i) a comparison against rituximab (RTX) in combination with methotrexate (MTX); (ii) a comparison against bDMARDs when RTX was contraindicated or withdrawn due to an adverse event; and (iii) a comparison against bDMARDs when MTX was contraindicated or withdrawn due to an adverse event. Results from the company's economic evaluation showed that CZP resulted in similar number of QALYs produced at similar, or lower, costs as comparator bDMARDs. The commercial-in-2 confidence patient access schemes for abatacept and tocilizumab could not be incorporated by the company, but were incorporated by the ERG in a confidential appendix for the NICE Appraisal Committee (AC). The company estimated that the addition of CZP before RTX in a sequence for patients who could receive MTX, produced more quality-adjusted life years (QALYs) at an increased cost, with a cost per QALY of £33,222. Following a critique of the model, the ERG undertook exploratory analyses that did not change the conclusions reached based on the company's economic evaluation in relation to the comparison with bDMARDs. The ERG estimated that where CZP replaced RTX, CZP was dominated, as it produced less QALYs at an increased cost. The AC concluded that there was little difference in effectiveness between CZP and comparator bDMARDs and that equivalence among bDMARDs could be accepted. The AC consequently recommended CZP plus MTX for people for whom RTX is contraindicated or not tolerated and CZP monotherapy for people for whom MTX is contraindicated or not to...

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“…In dieser Situation war Certolizumab Pegol mit einer ACR20-Antwort von 61,5 vs. 0% in der Placebogruppe signifikant überle-gen [39]. Diese Ansprechrate ist vergleichbar mit den Ergebnissen der REALISTICStudie, bei der eine Subgruppe von Patienten ebenfalls eine Vortherapie mit TNFBlockern hatte [48].…”

Section: Randomisierte Klinische Studien Offene Studien Sowie Beobacunclassified

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Rubbert-Roth

2015

Z Rheumatol

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Despite the use of biologics many patients do not achieve remission or reduced disease activity, which raises the question of the optimal therapy when these therapy targets are not achieved. Most data from clinical studies and registry data refer to the approach following the unsuccessful use of one or more tumor necrosis factor (TNF) inhibitors. Randomized controlled studies investigating the effectiveness of a further biologic or TNF inhibitor in patients who received abatacept, tocilizumab or rituximab in the first line therapy are currently lacking, with the exception of the German MIRAI study. The majority of registry data and observational studies suggest that when the use of a TNF inhibitor is unsuccessful it is advantageous to change to a non-TNF biologic. This does not exclude that a change within the group of TNF inhibitors can represent an appropriate option, e.g. by injection or infusion reactions or secondary therapy failure. Whether determination of serum levels and neutralizing antibodies aids decision-making for individual patients, must currently remain open. The option to change within an active ingredient group of biologics only currently applies to the group of TNF inhibitors; however, with the development of further antibodies inhibiting interleukin 6, this question will also apply to this group of substances. The question of the optimal strategy after failure of the first and second line biologics will be asked more frequently when the therapy targets of remission and low disease activity are more stringently strived for. Predictive markers for an optimal approach to the sequential administration of biologics are lacking. In order to answer this question clinical studies which investigate the therapeutic approach in a randomized and controlled manner will be necessary in the future.

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Efficacy and safety of certolizumab pegol in a broad population of patients with active rheumatoid arthritis: results from the REALISTIC phase IIIb study

Abstract: ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00717236.

Cited by 113 publications

References 16 publications

Levels of interleukin-1 beta can predict response to tocilizumab therapy in rheumatoid arthritis: the PETITE (predictors of effectiveness of tocilizumab therapy) study

Levels of interleukin-1 beta can predict response to tocilizumab therapy in rheumatoid arthritis: the PETITE (predictors of effectiveness of tocilizumab therapy) study

Certolizumab Pegol for Treating Rheumatoid Arthritis Following Inadequate Response to a TNF-α Inhibitor: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

Wechsel innerhalb der Wirkstoffgruppe oder Wechsel des Wirkprinzips

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