title: Golimumab: Review of the efficacy and tolerability of a recently approved tumor necrosis factor-α inhibitor.
abstract: BACKGROUND
  Golimumab (GLM) is a tumor necrosis factor-α (TNF-α) inhibitor that was approved in the United States in 2009 for use with methotrexate (MTX) in adults with moderate to severe active rheumatoid arthritis (RA), and with or without MTX or other non-biologic disease-modifying antirheumatic drugs in adults with active psoriatic arthritis (PsA) or active ankylosing spondylitis (AS). GLM is administered as a 50-mg subcutaneous injection once a month.
  
  
  OBJECTIVE
  The goals of this article were to review the current literature on GLM and to provide recommendations for the use of GLM based on the published information.
  
  
  METHODS
  The PubMed, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, International Pharmaceutical Abstracts, and other databases, as well as the Web sites for the American College of Rheumatology (ACR) and the European Union League Against Rheumatism, were searched for relevant articles published in English between the inception of the databases through April 2010. Search terms included golimumab and CNTO 148. Pharmacologic, pharmacokinetic, clinical, outcomes, and economic studies as well as meta-analyses, case reports, and select abstracts were eligible for inclusion. Review articles on GLM were not used except to identify other primary papers.
  
  
  RESULTS
  Seven clinical studies were identified and used to evaluate the efficacy and tolerability of GLM: 5 in patients with RA (4 subcutaneous administration and 1 intravenous administration), 1 in patients with PsA (subcutaneous), and 1 in patients with AS (subcutaneous). In MTX-naive patients with RA, the number of patients satisfying the ACR20 response criteria (>20% improvement in ACR response rate) at 24 weeks was significantly higher for the GLM + MTX groups than for the MTX-only groups (62% vs 49%, respectively; P < 0.05). In patients with active RA despite MTX therapy, ACR20 responses at 14 to 16 weeks were significantly higher for the combined GLM + MTX groups than for the MTX groups (50%-79% vs 33%-37%, respectively; P < 0.001). GLM was more effective than placebo, both with and without MTX, in patients with RA and a history of treatment with 1 or 2 TNF-α inhibitors (ACR20 at 14 weeks, 35%-37% vs 18%, respectively; P < 0.001). Studies of other TNF-α inhibitors reported ACR20 responses in 53% to 59% of patients with active RA at 24 weeks. GLM was also more effective than placebo at 24 weeks in patients with PsA (ACR20, 52%-61% vs 12%, respectively; P < 0.001) (ASAS40 [40% improvement based on Assessment in Ankylosing Spondylitis International Working Group criteria], 44%-54% vs 15%, respectively; P < 0.001). Studies of other TNF-α inhibitors reported ACR20 responses at 24 weeks in 55% to 57% of patients with PsA and ASAS40 responses in 46% to 47% of patients with AS. The incidence of any adverse effect appeared to be comparable in the GLM (61.2%-93.9%) and placebo groups (59.3%-85.3%), but withdrawals because of adverse effects were higher in the GLM groups (0%-12.1%) than in the placebo groups (0%-5.9%). The incidence of serious infections was comparable for GLM (0%-4.4%) and placebo (0.8%-3.5%). The most frequently reported adverse effects in the GLM groups were injection-site reactions (2.7%-37.1%), nausea (2.7%-22.9%), headache (3.8%-21.2%), nasopharyngitis (1.9%-15.0%), and upper respiratory tract infections (5.7%-13.8%).
  
  
  CONCLUSIONS
  Based on the results of the studies included in this review, GLM appeared to be more effective than placebo in patients with RA, PsA, or AS. Clinical studies have not directly compared GLM with other TNF-α inhibitors. However, according to the available efficacy and tolerability data, GLM should be considered as the first or second TNF-α inhibitor for the treatment of PsA or AS and as the second or possibly first TNF-α inhibitor in combination with MTX for the treatment of RA.
authors.affiliation: Department of Pharmacy Practice, University of the Pacific, Stockton, California, USA. eboyce@pacific.edu
authors.forename: Eric G
authors.initials: EG
authors.lastname: Boyce
authors.forename: Jenana
authors.initials: J
authors.lastname: Halilovic
authors.forename: Oby
authors.initials: O
authors.lastname: Stan-Ugbene
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D015535:Arthritis, Psoriatic / Q000188:drug therapy / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D017277:Drug Approval; D004359:Drug Therapy, Combination; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013167:Spondylitis, Ankylosing / Q000188:drug therapy / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000911:Antibodies, Monoclonal; D007155:Immunologic Factors; D014409:Tumor Necrosis Factor-alpha; C529000:golimumab; D008727:Methotrexate