Tumour Necrosis Factor Antagonists
Sarah H. Wakelin, Howard I. Maibach, Clive B. Archer in Handbook of Systemic Drug Treatment in Dermatology, 2015
Recently, new TNF antagonists such as golimumab and certolimumabpegol have been approved for rheumatological diseases. Golimumab, like adalimumab, is a fully human IgG1 antibody licensed for the treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Certolizumab-pegol is a humanized anti-TNF Fab’ fragment conjugated to a polyethylene glycol to prolong serum half-life, which facilitates once-monthly dosing. It is approved for the treatment of rheumatoid arthritis. As these two Adalimumab and infliximab bind to both sTNF and tmTNF, whereas etanercept binds primarily to sTNF and TNF-β. All three biological agents act by: (i) blocking TNF receptor mediated mechanisms and (ii) inducing tmTNF (reverse-signalling) events. In addition, adalimumab and infliximab can fix complement, thereby leading to antibody dependent cytotoxicity and can trigger T-cell apoptosis, whereas etanercept lacks these actions. Thus, adalimumab and infliximab seem to have a greater propensity to cause lymphocyte apoptosis compared with etanercept.
Compatibility of commonly used drugs in lactation
Amy Brown, Wendy Jones in A Guide to Supporting Breastfeeding for the Medical Profession, 2019
Babies of mothers with IBD on monoclonal antibodies should avoid live vaccines, especially rotavirus due to shedding into faeces. The mother is at risk of contracting virus from these. If vaccination is given, mother should wear gloves and be careful with hand hygiene. Infliximab – molecular weight 149,100. Poor oral bioavailability, RID 0.32–3.01%.Adalimumab – molecular weight 148,000. Poor oral bioavailability, RID 0.12%.Golimumab – molecular weight 150,000. Poor oral bioavailability.Certolizumab pegol – molecular weight 149,100. Poor oral bioavailability. RID 0.04–0.3%. Licensed for use in breastfeeding.
Viral Infections in Asthma
Jonathan A. Bernstein, Mark L. Levy in Clinical Asthma, 2014
Several mAbs have been studied in asthma, but specific information about respiratory viruses is largely unavailable in these studies. Omalizumab (mAb against immunoglobulin E [IgE], the key immunoglobulin involved in atopic and Th2 immune responses) decreases the rate of asthma exacerbations in adults and children compared with ICS alone. In addition to mAb anti-IgE, mAbs targeting other molecules in the Th2 inflammatory pathway have been investigated in clinical trials of asthmatic individuals, including mAbs anticytokines IL-4, IL-5, and IL-13; soluble receptor blockers for IL-4 showed potential to decrease asthma exacerbations, but larger studies did not confirm the initial results. Mepolizumab (mAb against IL-5) decreased asthma exacerbations in a study involving severe steroid-refractory asthmatics with sputum eosinophilia. Studies are ongoing to confirm its effectiveness in severe asthmatics with sputum eosinophilia. Similarly, lebrikizumab (mAb against IL-13) reduced asthma exacerbations in a “Th2-high” subgroup, characterized by elevated levels of periostin (an IL-13-induced protein). In contrast, golimumab (mAb against the proinflammatory cytokine TNF) showed no benefit in asthma exacerbations, and the study was stopped early due to adverse side effects, including concerns for an increased occurrence of malignancies. While little information is available regarding the identification of respiratory viruses in these studies, the efficacy of these mAbs in preventing virus-induced asthma exacerbations can be inferred from previous observations that the majority of asthma exacerbations appear to be associated with viruses.4
Biological treatment for erythrodermic psoriasis
Published in Expert Opinion on Biological Therapy, 2022
Golimumab is a fully human anti-TNF-α monoclonal antibody approved to treat psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis. Use of golimumab in psoriatic erythroderma was first reported by Lee et al. A 32-year-old man who had failed conventional oral therapies and phototherapy was treated with golimumab 50 mg [38]. Rapid response was noted as >50% reduction in PASI within 4 weeks. Efficacy was maintained at 11 months with monthly golimumab injections without any significant adverse effects. Kudsi et al. described rapid response to golimumab in two EP patients [39]. PASI score improved in both patients from 39.1 and 41.9 at baseline to 17.1 and 14.8 at 4 weeks, respectively. Psoriatic exfoliative erythroderma following golimumab injection for rheumatoid arthritis has been described [40].
Effect of biological DMARDs and JAK inhibitors in pain of chronic inflammatory arthritis
Published in Expert Opinion on Biological Therapy, 2022
Alessandra Alciati, Marco Di Carlo, Cesare Siragusano, Antonino Palumbo, Ignazio Francesco Masala, Fabiola Atzeni
Certolizumab pegol is the first poly (ethylene glycol) (PEG)ylated, Fc-free anti-TNFα. The attachment of a PEG chain to the Fab′ fragment increases its half-life to a mean of 14 days, allowing a once-a-month subcutaneous dosing regimen. In the 24-week FAST4WARD trial, certolizumab pegol showed a rapid efficacy of action on pain, with a reduction of 16.7 on a VAS 0–100 scale just after 1 week of treatment and 20.6 at the end of the study [33]. Golimumab is a transgenic and anti-TNF monoclonal antibody that acts primarily by targeting and neutralizing TNFα, thus preventing inflammation. The GO-AFTER study, that considered aggregated data for the 50 and 100 mg dosages of golimumab, documented a reduction in VAS pain (0–10 cm) of 30.9% at 14 weeks and 32% at 24 weeks [34].
Postmarketing surveillance evaluating the safety and effectiveness of golimumab in Japanese patients with rheumatoid arthritis
Published in Modern Rheumatology, 2018
Masayoshi Kanbori, Hiroshi Suzuka, Tsutomu Yajima, Emika Kishino, Ryuji Morishige, Shigeki Momohara, Atsushi Kawakami, Miyo Ota
Golimumab (GLM), a human monoclonal antibody, targets a unique epitope on the tumor necrosis factor-α (TNF) molecule. It binds with high affinity to both the soluble and membrane-bound forms of TNF, creating stable, high-affinity complexes and preventing the binding of TNF to its receptors [3,4]. Previous multicenter, phase-III clinical trials, GO-FORWARD, GO-AFTER and GO-BEFORE, have demonstrated the safety and efficacy of GLM along with methotrexate (MTX) in patients with active RA [5–8] and two clinical trials, GO-FORTH and GO-MONO, were conducted in patients with active RA in Japan [9,10]. In July 2011, GLM was approved in Japan for the treatment of patients with RA who demonstrated inadequate response to conventional therapy based on the results of clinical trials. Two doses were adopted: 50 mg or 100 mg of GLM concomitantly with MTX or 100 mg of GLM without MTX. The Pharmaceuticals and Medical Devices Agency (PMDA) approved the 100 mg of GLM without MTX but not 50 mg of GLM without MTX. Of note, the clinical response to GLM without MTX in the GO-MONO study was relatively modest in contrast to GLM with concomitant MTX in the GO-FORTH study [10].
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