Long-term treatment of rheumatoid arthritis with adalimumab

Open Access Rheumatology: Research and Reviews Dovepress open access to scientific and medical research R evie w Open Access Full Text Article Open Access Rheumatology: Research and Reviews downloaded from https://www.dovepress.com/ For personal use only. Long-term treatment of rheumatoid arthritis with adalimumab This article was published in the following Dove Press journal: Open Access Rheumatology: Research and Reviews 7 May 2013 Number of times this article has been viewed Giuseppe Murdaca Francesca Spanò Francesco Puppo Department of Internal Medicine, Clinical Immunology Unit, University of Genoa, Genoa, Italy Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease that is associated with joint damage and progressive disability, an increased risk of morbidity related to comorbid conditions and substantial socioeconomic costs. Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine known to have a central role in the initial host response to infection and in the pathogenesis of various immune-mediated diseases, such as RA, ankylosing spondylitis, psoriasis and/or psoriatic arthritis, Crohn’s disease, and systemic lupus erythematosus. Five TNF-α inhibitors are available for the clinical use: infliximab; adalimumab; etanercept; golimumab; and certolizumab pegol. Infliximab is a chimeric human/murine IgG1 monoclonal antibody (mAb); adalimumab, and golimumab are human mAbs; certolizumab pegol is composed of the fragment antigen-binding anti-binding domain of a humanized anti-TNF-α mAb, combined with polyethylene glycol to increase its half-life in the body; etanercept is a fusion protein that acts as a “decoy receptor” for TNF-α. In this paper, we will briefly review the current data on efficacy and safety of adalimumab in patients with RA, its potential beneficial effects upon comorbid conditions, such as endothelial dysfunction and accelerated atherosclerosis in RA, and the immunogenicity. Keywords: adalimumab, efficacy, safety, rheumatoid arthritis, VEGF, immunogenicity, infections Introduction Correspondence: Giuseppe Murdaca Department of Internal Medicine, Clinical Immunology Unit, University of Genoa, Viale Benedetto XV, 16132 Genoa, Italy Tel +39 010 353 7924 Fax +39 010 555 6950 Email submit your manuscript | www.dovepress.com Dovepress http://dx.doi.org/10.2147/OARRR.S32582 Rheumatoid arthritis (RA) is a chronic inflammatory immune-mediated disease that is burdened by progressive joint damage and disability, increased risk of comorbidity and socioeconomic costs.1–3 The ongoing progresses in the knowledge of the pathogenic mechanisms of various immune-mediated diseases, such as RA, ankylosing spondylitis (AS), psoriasis (Ps) and/or psoriatic arthritis (PsA), Crohn’s disease (CD), systemic lupus erythematosus (SLE), and the availability of innovative biotechnological approaches, have led to the development of new drugs that add to conventional treatments. In particular, efforts have been made to design biologic drugs that are able to counteract the activity of different molecules (ie, tumor necrosis factor-α [TNF-α], interleukin 1 (IL-1), CD20, CD22, and CD11a). TNF-α is a proinflammatory cytokine known to have a central role in the initial host response to infection and in the pathogenesis of the above-mentioned diseases.4 TNF-α inhibitors have demonstrated efficacy in large, randomized controlled clinical trials either as monotherapy or in combination with other anti-inflammatory or disease modifying antirheumatic drugs (DMARDs).5–10 Five TNF-α inhibitors are available for the clinical use: infliximab, adalimumab, etanercept, golimumab, and certolizumab pegol. All these agents block the biologic effects of TNF-α, although there are some differences in Open Access Rheumatology: Research and Reviews 2013:5 43–49 43 © 2013 Murdaca et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. Murdaca et al their structure, pharmacokinetics, and mechanisms of action. The efficacy and safety profile of the TNF-α inhibitors can be considered, in general, as a class effect. Nevertheless, some differences may exist among the five agents. Infliximab is a chimeric human/murine IgG1 monoclonal antibody (mAb), adalimumab, and golimumab are human mAbs, certolizumab pegol is composed of the fragment antigenbinding (Fab) domain of a humanized anti-TNF-α mAb combined with polyethylene glycol to increase its half-life in the body, etanercept is a fusion protein that acts as a “decoy receptor” for TNF-α.5–12 In particular, adalimumab is a fully recombinant human IgG1 anti-TNF-α -specific mAb which is approved for the treatment of Ps, PsA, RA, AS, and CD.5–12 However, the efficacy and safety of adalimumab administered as monotherapy or in combination with methotrexate (MTX) for the treatment of RA has been well-established in clinical trials.13–19 In this paper, we will briefly review the current data upon efficacy and safety of adalimumab in patients with RA, its potential beneficial effects upon comorbid conditions, such as endothelial dysfunction and accelerated atherosclerosis in RA, and the immunogenicity. Efficacy and safety of adalimumab: how to optimize the treatment of RA Adalimumab is a fully recombinant human immunoglobulin G1 (IgG1) anti-TNF-α-specific mAb that is capable of complement fixation and fragment crystallizable-(Fc) receptor binding. The plasma half-lives of antibodies appear to be largely related to the binding of their Fc regions to the neonatal Fc receptors (FcRn) on endothelial cells. The long plasma half-life of adalimumab suggests that it binds to FcRn like natural IgG1 molecules. Adalimumab is usually administered subcutaneously (40 mg every other week). 5–12 Adalimumab was approved by the US Food and Drug Administration (FDA) in 2002 and was granted approval from the European Medicines Agency (EMA) in September 2003 for the treatment of RA. Adalimumab was subsequently approved by the FDA for the following indications: PsA (in 2005), AS (in 2006), and CD (in 2007), as well as for juvenile-idiopathic RA and chronic plaque Ps, (both in 2008). Adalimumab is also approved for the treatment of these diseases by the EMA.5–12 Patients with RA must meet the following criteria before TNF-α inhibitors can be administered: 1. failure to respond to an adequate trial of at least two DMARDs, including MTX at an optimal dose (at least 44 submit your manuscript | www.dovepress.com Dovepress Dovepress 15 mg/week and maximum dose 25 mg/week) for a minimum of 3 months, or intolerance for MTX; 2. clinical evidence of active disease (multiple actively inflamed joints and/or Disease Activity Score uses 28 joint counts [DAS28] .3.2); 3. persistently elevated inflammatory markers, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP).8,20 Notably, DAS28 has been widely used to monitor the di (...truncated)