Safety and efficacy of ocrelizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: Results of a forty‐eight–week randomized, double‐blind, placebo‐controlled, parallel‐group phase III trial

Rigby, William F.C.; Tony, Hans‐Peter; Oelke, Kurt; Combe, Bernard; Laster, Andrew J.; Mühlen, Carlos Alberto von; Fisheleva, Elena; Martín, Carmen; Travers, Helen; Dummer, Wolfgang

doi:10.1002/art.33317

Cited by 68 publications

(54 citation statements)

References 36 publications

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“…However, the increased depletion of normal B cells will need to be balanced against potential complications of prolonged immunosuppression. Such problems have already been encountered in patients with autoimmune diseases receiving second-generation CD20 MAbs [Rigby et al 2011].…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of ofatumumab in patients with fludarabine and alemtuzumab refractory chronic lymphocytic leukaemia

Dyer

2012

Therapeutic Advances in Hematology

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There are now many therapeutic CD20 monoclonal antibodies undergoing clinical trials for B-cell malignancy and autoimmune conditions; which is optimal for cancer therapy is not clear. The novel human IgG1 CD20 monoclonal antibody ofatumumab has shown significant activity in difficult to treat patients with chronic lymphocytic leukemia, namely those resistant or refractory to fludarabine and alemtuzumab and has now been licensed for this uncommon indication. This brief review summarizes the clinical data obtained with ofatumumab in CLL in terms of both efficacy and toxicity.

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Section: Discussionmentioning

confidence: 99%

Safety and efficacy of ofatumumab in patients with fludarabine and alemtuzumab refractory chronic lymphocytic leukaemia

Dyer

2012

Therapeutic Advances in Hematology

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“…These data are similar to those observed for rituximab in MTX-naive patients with RA7 and in two related OCR phase III trials, STAGE and SCRIPT. In STAGE, OCR 200 mg and 500 mg each significantly inhibited radiographic progression over 48 weeks versus placebo in patients with an inadequate response to MTX 9. In SCRIPT, which studied a more refractory TNF-IR population, only OCR 500 mg significantly inhibited structural damage progression 10.…”

Section: Discussionmentioning

confidence: 99%

Safety and efficacy of ocrelizumab in combination with methotrexate in MTX-naive subjects with rheumatoid arthritis: the phase III FILM trial

Stohl

Gómez-Reino²,

Olech

et al. 2012

Ann Rheum Dis

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ObjectiveTo determine the efficacy and safety of ocrelizumab (OCR) with methotrexate (MTX) in MTX-naive rheumatoid arthritis (RA) patients.MethodsIn a randomised, double-blind, controlled trial, patients received placebo+MTX (MTX; n=210), OCR 200 mg×2+MTX (OCR 200; n=200) or OCR 500 mg×2+MTX (OCR 500; n=203). OCR/placebo (two intravenous infusions) was given on days 1 and 15, with fixed re-treatment scheduled at weeks 24/26, 52/54 and 76/78. Due to early termination of OCR dosing, there was no formal primary end point analysis (change from baseline in modified total Sharp score (ΔmTSS) at week 104). Analyses are reported for week 52 outcomes.ResultsAt week 52, treatment with OCR+MTX compared with MTX alone reduced progression of joint damage (mean (SD) change in ΔmTSS: OCR 200, 0.66 (4.51); OCR 500, 0.27 (2.91); MTX alone, 1.59 (4.82); p=0.001 and p=0.003, respectively vs MTX alone) and improved clinical signs and symptoms (American College of Rheumatology 20 response: OCR 200, 73.0%; OCR 500, 71.0%; MTX alone, 57.5%; p<0.005 for each OCR vs MTX alone). Serious infection rates per 100 patient-years were similar with OCR 200 and MTX alone (2.6 (95% CI 0.9 to 6.1) and 3.0 (1.1 to 6.5), respectively), but higher with OCR 500 (7.1 (3.9 to 11.9)).ConclusionsOCR 200 mg and 500 mg with MTX in MTX-naive patients with RA were effective in inhibiting joint damage progression and improving RA signs and symptoms. OCR 500 mg with MTX was associated with an increased rate of serious infections.

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“…[15] A phase III trial in rheumatoid arthritis enrolling patients receiving concomitant immunosuppressive medications (such as methotrexate or leflunomide) reported high rates of infections, especially with the 500 mg regimen, and some of those infections resulted in death. [85][86][87] There were no reported opportunistic infections in the phase II trial. Adverse events reported were similar between the treatment groups; however, there was one death in the 2000 mg arm.…”

Section: Monoclonal Antibodiesmentioning

confidence: 97%

Advances in the treatment of relapsing - Remitting multiple sclerosis

Tanasescu¹,

Ionete²,

Chou³

et al. 2014

Biomed J

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Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system (CNS). Pathologic hallmarks of MS lesions are inflammation, demyelination, axonal degeneration, neuronal loss, and gliosis. [1,2] MS is the most common neurological non-traumatic cause of disability in young people in the western world. MS initially presents in most patients as a relapsing-remitting condition (RRMS), but the majority of RRMS individuals develop a secondary progressive course (SPMS) later. [3] In fewer cases, the disease progresses from the beginning without superimposed relapses [primary progressive MS (PPMS)] or with rare superimposed relapses [progressive relapsing MS (PRMS)]. [4] The clinical signs in MS can occur in isolation or in combination, and can include motor and sensory deficits, partial or complete visual loss, diplopia, impaired coordination, and gait dysfunction. The diagnosis specifically integrates magnetic resonance imaging (MRI) with clinical attacks and paraclinical methods, and implies the dissemination of inflammatory activity in time and space. [5] MS treatments tackle separately the acute exacerbations and their prevention. Pharmacological management of relapses involves the use of corticosteroids, while approved long-term treatments [disease-modifying treatments (DMTs)] aim to decrease the clinical relapse rate and concomitant inflammation within the CNS.MS therapeutic landscape is changing rapidly. After several years in which first-line DMTs -glatiramer acetate (GA) and interferon β (IFNβ) -constituted the principal treatment options, a variety of new agents for MS treatment are now approved by regulatory authorities or in phase II and III clinical trials.[6] In 2010, fingolimod, the first oral agent, Special EditionThis article reviews and discusses the approved and emerging therapies for multiple sclerosis (MS). MS is a chronic and disabling immune-mediated disease of the central nervous system (CNS) that affects mainly young adults. MS imposes a huge economic burden on healthcare systems and the society. Although the last 20 years have brought a continuous expansion in therapeutic options, there are still unmet needs in MS management. Available MS drugs have varying degrees of efficacy in reducing relapse risk. The long-term term effects of these treatments are incompletely known. New therapies, along with variations of currently available treatments, may prove more effective and tolerable than the available drugs. Treatments for MS differ with respect to the mode of administration, tolerability and likelihood of treatment adherence, side effects, and risk of major toxicity. The armamentarium of approved disease-modifying therapies in MS and those in development include: (1) the first approved, moderately effective, injectable interferon-β and glatiramer acetate; (2) oral drugs (fingolimod, laquinimod, teriflunomide, dimethyl fumarate); (3) monoclonal antibodies (rituximab, ocrelizumab, ofatumumab, daclizumab, alemtuzumab); and (4) immunosuppressive agents (e.g. mitoxantrone)...

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Safety and efficacy of ocrelizumab in patients with rheumatoid arthritis and an inadequate response to methotrexate: Results of a forty‐eight–week randomized, double‐blind, placebo‐controlled, parallel‐group phase III trial

Cited by 68 publications

References 36 publications

Safety and efficacy of ofatumumab in patients with fludarabine and alemtuzumab refractory chronic lymphocytic leukaemia

Safety and efficacy of ofatumumab in patients with fludarabine and alemtuzumab refractory chronic lymphocytic leukaemia

Safety and efficacy of ocrelizumab in combination with methotrexate in MTX-naive subjects with rheumatoid arthritis: the phase III FILM trial

Advances in the treatment of relapsing - Remitting multiple sclerosis

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