title: Safety and efficacy of ocrelizumab in rheumatoid arthritis patients with an inadequate response to methotrexate or tumor necrosis factor inhibitors: a systematic review and meta-analysis.
abstract: We conducted this systematic reviews and meta-analysis to investigate the safety and efficacy of ocrelizumab in patients with active rheumatoid arthritis (RA) who exhibited resistance or intolerance to methotrexate or biological therapy. We performed a web-based literature search of PubMed, Google Scholar, EBSCO, Scopus, Embase, and Web of science for studies that compared ocrelizumab plus methotrexate versus methotrexate plus placebo in RA patients. Data were extracted from eligible studies and pooled as risk ratios (RR), using RevMan software. Pooling data from four RCTs (2230 patients) showed that ocrelizumab plus methotrexate were superior to methotrexate plus placebo at 24 weeks in terms of improvement on the American college of rheumatology (ACR20, ACR50, and ACR70) criteria (p < 0.00001), disease activity score 28-ESR (RR = 3.77, 95% CI [2.47, 5.74], p < 0.00001), and Sharp/van der Heijde radiological score (RR = 1.63, 95% CI [1.43, 1.85], p < 0.00001). These effects were consistent among all ocrelizumab doses. The rates of serious adverse events were comparable between the ocrelizumab and placebo containing groups (RR = 1, 95% CI [0.78, 1.28], p = 0.98). However, infusion related reactions were significantly higher in ocrelizumab group (RR = 2.13, 95% CI [1.69, 2.68], p < 0.00001), compared to placebo group. The combination of ocrelizumab plus methotrexate was superior to methotrexate plus placebo on all clinical and radiographic improvement scales. The incidence of adverse events, including serious adverse events, was comparable between both groups. Future trials should investigate the efficacy of ocrelizumab alone and develop strategies to alleviate its related infusion reactions.
authors.affiliation: Faculty of Medicine, Ain Shams University, Ramsis St, Abbasia, Cairo, 11591, Egypt. Abdelrahman.abushouk@med.asu.edu.eg.|NovaMed Medical Research Association, Cairo, Egypt. Abdelrahman.abushouk@med.asu.edu.eg.|Medical Research Group of Egypt, Cairo, Egypt. Abdelrahman.abushouk@med.asu.edu.eg.
authors.forename: Abdelrahman Ibrahim
authors.initials: AI
authors.lastname: Abushouk
authors.affiliation: Medical Research Group of Egypt, Cairo, Egypt.|Faculty of Medicine, Zagazig University, El Sharkia, Egypt.
authors.forename: Hussien
authors.initials: H
authors.lastname: Ahmed
authors.affiliation: NovaMed Medical Research Association, Cairo, Egypt.|Medical Research Group of Egypt, Cairo, Egypt.|Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
authors.forename: Ammar
authors.initials: A
authors.lastname: Ismail
authors.affiliation: NovaMed Medical Research Association, Cairo, Egypt.|Medical Research Group of Egypt, Cairo, Egypt.|Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Elmaraezy
authors.affiliation: Medical Research Group of Egypt, Cairo, Egypt.|Faculty of Medicine, Menoufia University, Menoufia, Egypt.|Student Research Unit, Menoufia University, Menoufia, Egypt.
authors.forename: Ahmed Said
authors.initials: AS
authors.lastname: Badr
authors.affiliation: Medical Research Group of Egypt, Cairo, Egypt.|Faculty of Medicine, Alexandria University, Alexandria, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Gadelkarim
authors.affiliation: Medical Research Group of Egypt, Cairo, Egypt.|Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Elnenny
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D001688:Biological Products / Q000009:adverse effects / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D004351:Drug Resistance; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D006801:Humans; D000075662:Injection Site Reaction / Q000209:etiology; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D016017:Odds Ratio; D012307:Risk Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001688:Biological Products; D014409:Tumor Necrosis Factor-alpha; C533411:ocrelizumab; D008727:Methotrexate
keywords: B cell; Methotrexate; Ocrelizumab; Rheumatoid arthritis