TNFα has a key role in cell recruitment, proliferation and death, expression of adhesion molecules and immune responses. In RA, TNFα is involved in matrix degradation and osteoclastogenesis. TNFα inhibitors are either soluble receptors (etanercept) or monoclonal antibodies (infliximab and adalimumab; golimumab and certolizumab are in development). TNFα antagonists, alone or in combination with methotrexate, reduce bone erosions and thinning of cartilage, but they differ as regards ligand binding, pharmacokinetics, pharmacodynamics, and clinical indications. Etanercept is the only TNFα antagonist that also neutralises LFT-α. Infliximab and adalimumab are more immunogenic. Cytotoxicity and cellular lysis are also higher with infliximab and adalimumab. Etanercept slows progression of joint damage in recently diagnosed RA when given alone, but much more when given with methotrexate; anti-TNF monoclonal antibodies also were shown to slow progression alone and in combination with methotrexate. Patients with early and long-standing RA treated with etanercept have now shown improvement in ACR scores, inflammation and disability for up to 9 years. Outcomes with infliximab and adalimumab are similar to those with etanercept, but only in combination with methotrexate. As a result of neutralizing antibodies, increasing doses of anti-TNFα antibodies may be required to maintain clinical response. As regards side effects, opportunistic infections seem more frequent with monoclonal antibodies. TNFα antagonists produce more QALYs than traditional DMARDs, counteracting higher costs. The efficacy, safety, and quality of life benefits of TNFα antagonists suggest using them possibly earlier than today, even in clinically moderate RA.
La rivoluzione copernicana nella terapia dell’artrite reumatoide: il contributo degli anti-TNFα
TROTTA, Francesco;
2009
Abstract
TNFα has a key role in cell recruitment, proliferation and death, expression of adhesion molecules and immune responses. In RA, TNFα is involved in matrix degradation and osteoclastogenesis. TNFα inhibitors are either soluble receptors (etanercept) or monoclonal antibodies (infliximab and adalimumab; golimumab and certolizumab are in development). TNFα antagonists, alone or in combination with methotrexate, reduce bone erosions and thinning of cartilage, but they differ as regards ligand binding, pharmacokinetics, pharmacodynamics, and clinical indications. Etanercept is the only TNFα antagonist that also neutralises LFT-α. Infliximab and adalimumab are more immunogenic. Cytotoxicity and cellular lysis are also higher with infliximab and adalimumab. Etanercept slows progression of joint damage in recently diagnosed RA when given alone, but much more when given with methotrexate; anti-TNF monoclonal antibodies also were shown to slow progression alone and in combination with methotrexate. Patients with early and long-standing RA treated with etanercept have now shown improvement in ACR scores, inflammation and disability for up to 9 years. Outcomes with infliximab and adalimumab are similar to those with etanercept, but only in combination with methotrexate. As a result of neutralizing antibodies, increasing doses of anti-TNFα antibodies may be required to maintain clinical response. As regards side effects, opportunistic infections seem more frequent with monoclonal antibodies. TNFα antagonists produce more QALYs than traditional DMARDs, counteracting higher costs. The efficacy, safety, and quality of life benefits of TNFα antagonists suggest using them possibly earlier than today, even in clinically moderate RA.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
