Treatment psoriasis with immunobiologics

Based on the recent advances in our understanding of the pathogenesis and pathophysiology of psoriasis, there was accompanying research into the development and use of biologic response modifiers for psoriasis and psoriatic arthritis Some biologic response modifiers have proven efficacy for psoriasis; however, there are differences among these agents, including mechanism of action, duration of remission, and adverse-effect profile. Currently, biologic response modifiers are often considered for patients with moderate to severe psoriasis when other systemic agents are inadequate. It has also been recommended that biologic response modifiers be considered as first-line therapy, alongside conventional systemic agents, for patients with moderate to severe psoriasis; however, in practice, cost may be a limiting factor. Biologic response modifiers with proven efficacy for psoriasis include alefacept, etanercept, and efalizumab. These agents employ the following targeted immunosuppressive strategies: alefacept inhibits T-cell activation by targeting LFA-3–CD2 and inducing apoptosis in memory T cells, etanercept inhibits T1 cytokines by targeting tumor necrosis factor-α, and efalizumab inhibits T-cell activation by targeting CD11a, the α subunit of LFA-1 (ICAM-1). Other biologic agents in clinical trials for psoriasis include infliximab, adalimumab, HuMax CD4, siplizumab, daclizumab, and denileukin diftitox .

 In general, due to their immunosuppressive effects, there is an increased risk of infection with most of these agents. The use of live or liveattenuated vaccines during therapy is generally not recommended.

Alefacept (Amevive) is a recombinant fusion protein composed of LFA- 3 linked to the constant portion of human IgG is a dimeric fusion protein that binds to CD2 on T cells to inhibit cutaneous T-cell activation and proliferation. It also produces a dose dependent decrease in circulating total lymphocytes. It also interacts with natural killer cells to destroy already activated T cells  Alefacept is approved for treatment of moderate to severe plaque psoriasis and is also effective for treatment of psoriatic arthritis. Significant response is usually achieved after about 3 months of therapy . The recommended dose is 15 mg intramuscularly once weekly for 12 weeks. Adverse effects are mild and include pharyngitis, flu-like symptoms, chills, dizziness, nausea, headache, injection site pain and inflammation, and nonspecific infection.

 alefacept

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Ustekinumab (Stelara) Human monoclonal antibody directed against IL-12 and IL-23, thereby interfering with T-cell differentiation and activation and subsequent cytokine cascades. Indicated for moderate-to-severe plaque psoriasis . Serious adverse effects include infection risk and reactivation of latent infections (including TB), malignancy, or reversible posterior leukoencephalopathy syndrome (rare); common adverse effects include upper respiratory tract infection, nasopharyngitis, headache, and fatigue. The recommended dose for less than 100 kg is 45 mg subcutaneously (SC)  initially, repeat in fourth week, then 45 mg SC every 12 week . The recommended dose for more than 100 kg is 90 mg subcutaneously (SC)  initially, repeat in fourth week, then 90 mg SC every 12 week .

 ustekinumab

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Ustekinumab Side Effects

Efalizumab (Raptiva) is a humanized monoclonal antibody that inhibits CD11-α integrin the α subunit of leukocyte-function-associated antigen type 1 [LFA-1], which is involved in T-cell activation, migration into skin, and cytotoxic function. It is approved for adults with chronic, moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. The recommended dose is a single 0.7 mg/kg subcutaneous conditioning dose followed by weekly subcutaneous doses of 1 mg/kg (200 mg maximum single dose) at 12 weeks of treatment. The most frequent adverse effects are mild to moderate flu-like complaints such as headache, nausea, chills, nonspecific infection, pain, fever, and asthenia. Cases of exacerbation of psoriasis on discontinuation have been reported, leading to the suggestion that continuous treatment may be required to maintain disease suppression. , is being withdrawn from the US market and will no longer be available after June 8, 2009, because of potential risk for progressive multifocal leukoencephalopathy (PML).

efalizumab

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Tumor necrosis factor inhibitors                                               

Infliximab (Remicade) is a chimeric monoclonal antibody directed against TNF- α. Recently, its indications have been expanded to include psoriatic arthritis and treatment of adults with chronic severe plaque psoriasis. An advantage over other systemic psoriasis treatments is that infliximab does not adversely affect blood counts, hepatic enzyme levels, or kidney function. The recommended dose is 5 mg/kg as an IV infusion at weeks 0, 2, and 6, then every 8 weeks thereafter. For psoriatic arthritis, it may be used with or without methotrexate. Adverse effects include headaches, fever, chills, fatigue, diarrhea, pharyngitis, upper respiratory and urinary tract infec tions. Hypersensitivity reactions (urticaria, dyspnea, hypotension) and lymphoproliferative disorders have been reported

infliximab 

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Infliximab Side Effects 

Etanercept (Enbrel) A recombinant human TNF-alpha (TNF-α p75 ) receptor protein fused with Fc portion of IgG1 (cell-bound receptors ) that binds to soluble and membrane bout TNF-alpha, thereby neutralizing the effects of TNF-alpha , This agent is useful for chronic moderate to severe plaque psoriasis and for psoriatic arthritis Unlike the chimeric infliximab, etanercept is fully humanized, thereby minimizing the risk of immunogenicity. Etanercept is FDA approved for reducing signs and symptoms and inhibiting the progression of joint damage in patients with psoriatic arthritis. It can be used in combination with methotrexate in patients who do not respond adequately to methotrexate alone. It is also indicated for adult patients with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. The recommended dose for psoriatic arthritis is 50 mg subcutaneously once per week. For plaque psoriasis, the dose is 50 mg subcutaneously twice weekly (administered 3 or 4 days apart) for 3 months followed by a maintenance dose of 50 mg per week. Adverse effects include local reactions at the injection site (20% of patients), respiratory tract and GI infections, abdominal pain, nausea and vomiting, headaches, and rash Serious infections (including tuberculosis) and malignancies are rare.

etanercept

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Etanercept Side Effects

Adalimumab (Humira) is a human immunoglobulin G1 monoclonal TNF- α antibody. The binding of adalimumab results in inactivation of the proinflammatory cytokine TNF- α. It is indicated for psoriatic arthritis and treatment of adults with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy. The recommended dose for psoriatic arthritis is 40 mg subcutaneously every other week. The recommended dose for adults with plaque psoriasis is an initial dose of 80 mg, followed by 40 mg every other week starting 1 week after the initial dose. The most common adverse reactions are infections (e.g., upper respiratory, sinusitis), injection site reactions, headache, and rash.

 adalimumab

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Adalimumab Side Effects