Certolizumab Pegol in Patients With Moderate to Severe Crohn's Disease and Secondary Failure to Infliximab

Mayo Clinic, Rochester, Minnesota, USA.
Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association (Impact Factor: 7.9). 05/2010; 8(8):688-695.e2. DOI: 10.1016/j.cgh.2010.04.021
Source: PubMed


Patients with moderate to severe Crohn's disease who receive infliximab may experience secondary failure (loss of response and/or hypersensitivity). Data on the utility of switching to certolizumab pegol in these patients are limited.
A total of 539 patients with active Crohn's disease and secondary failure to infliximab were enrolled in a 26-week trial. Patients received open-label induction with subcutaneous certolizumab pegol 400 mg at weeks 0, 2, and 4. Those in clinical response at week 6 were randomized to certolizumab pegol 400 mg every 2 or every 4 weeks through week 24. The primary end point was response at week 6. Secondary end points included remission at week 6 and response and remission at week 26.
At week 6, 334 of 539 patients (62.0%) achieved response and 212 of 539 (39.3%) achieved remission. A total of 329 patients were randomized and received maintenance therapy. At week 26, 39.9% (67 of 168) and 36.6% (59 of 161) of patients in the every-4-weeks and every-2-weeks groups were in clinical response, respectively (P = .55). Corresponding remission rates at week 26 were 29.2% and 30.4%, respectively (P = .81). Serious infections occurred in 9 of 539 (1.7%) and 12 of 373 (3.2%) of patients during induction and maintenance, respectively. A single malignancy (skin carcinoma) occurred in a patient receiving every-4-weeks maintenance therapy.
Response to open-label induction therapy with certolizumab pegol was achieved by 62% of patients with moderate to severely active Crohn's disease and secondary failure to infliximab. Among these patients, certolizumab pegol 400 mg every 4 weeks showed similar efficacy to every-2-weeks dosing for maintenance of response and remission.

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    • "The 26-Week open-label trial evaluating the clinical benefit and tolerability of certolizumab pegol induction and maintenance in patients suffering from Crohn’s disease with prior loss of response or intolerance to infliximab (WELCOME) trial evaluated the clinical benefits and tolerability of certolizumab pegol over 26 weeks in patients with moderate to severe CD with prior LoR and/or hypersensitivity to IFX.61 At week 6, 62% of patients achieved a 100-point decrease (64.3% in patients with prior LoR to IFX) and 69.2% achieved a 70-point or greater decrease in Crohn’s Disease Activity Index scores from baseline, with a clinical remission rate (Crohn’s Disease Activity Index score ≤150 points) reported in 39.3% of patients. "
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    ABSTRACT: Dovepress 359 R E v i E w open access to scientific and medical research Open Access Full Text Article Abstract: Infliximab (IFX) is an effective treatment for inducing and maintaining response in Crohn's disease and ulcerative colitis patients. Some patients present lack of response or loss of response to IFX during maintenance therapy. Empirical management with combination therapy with an immunomodulator, IFX dose escalation, or switching IFX for another antitumor necrosis factor-α drug, mainly adalimumab, is common in clinical practice. Selecting the best choice with the help of serum drug concentrations and trough IFX antibody concentrations could be a very interesting approach. In addition to surgery, a broad spectrum of new drugs has been tested and could expand treatment options in the near future.
    Clinical and Experimental Gastroenterology 09/2014; 7. DOI:10.2147/CEG.S45297
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    • "While anti-TNFα therapies have been a significant advance in the management of CD, significant proportions (up to 40%) of patients do not respond to induction therapy (primary nonresponders).14 Among patients who respond to induction therapy with an anti-TNFα agent, almost half lose response and/or develop hypersensitivity reactions (secondary nonresponders).15 Patients with a primary nonresponse are unlikely to benefit from switching to a second anti-TNFα agent. "
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    ABSTRACT: The advent of anti-tumor necrosis factor (TNF)-α therapy has been a major advance in the medical management of Crohn's disease (CD). However, a significant proportion of patients with CD do not respond adequately to treatment with these agents. Primary and secondary nonresponse to anti-TNFα therapy represents a common clinical challenge, and highlights the need for the development of additional medication options for CD. The proinflammatory cytokines interleukin (IL)-12 and IL-23 are thought to play a key role in the pathogenesis of CD, and serve as a potential target for additional biologic therapies. Monoclonal antibodies targeting IL-12/23 have shown efficacy in animal models of colitis, and are currently being studied in Phase III clinical trials of CD. This review focuses on ustekinumab, a fully human immunoglobulin G1 monoclonal antibody, which blocks activity of IL-12 and IL-23 through binding the p40 subunit, and describes the current efficacy and safety data for ustekinumab in patients with CD.
    Clinical and Experimental Gastroenterology 05/2014; 7(1):173-179. DOI:10.2147/CEG.S39518
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    • "Data from three studies involving patients with Crohn’s disease has noted the development of antibodies directed against CZP in 6%–12% of patients receiving it.61–63 The presence of antibodies did not adversely affect response to therapy, even when associated with lower plasma concentrations of CZP; antibody levels were low in patients receiving concomitant immunosuppressant therapy.61 "
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    ABSTRACT: The axial spondyloarthropathies are a group of chronic inflammatory diseases that predominantly affect the axial joints. This group includes ankylosing spondylitis and nonradiographic axial spondyloarthropathy. While the pathogenesis of axial spondyloarthropathies is not clear, immunologically active tissues primarily include the entheses, ie, the areas where ligaments, tendons, and joint capsules attach to bone and to the annulus fibrosis at the vertebrae. One of the major mediators of the immune response in this group of diseases is tumor necrosis factor-alpha (TNFα). Blockade of TNFα results in reduced vascularity and inflammatory cell infiltration in the synovial tissues of affected joints. Certolizumab pegol (CZP) is an Fc-free, PEGylated anti-TNFα monoclonal antibody. CZP has unique properties that differ from other available TNFα inhibitors by virtue of its lack of an Fc region, which minimizes potential Fc-mediated effects, and its PEGylation, which improves drug pharmacokinetics and bioavailability. It has been shown in clinical trials that CZP improves patient outcomes and reduces inflammation in the sacroiliac joints and spine in both ankylosing spondylitis and nonradiographic axial spondyloarthropathies. These data support CZP as a treatment option for axial spondyloarthropathies.
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