New treatment option for severe plaque psoriasis

Abstract

A new treatment for plaque psoriasis, ixekizumab (Taltz—Eli Lilly), was recently approved for adults with moderate to severe disease. This agent targets interleukin-17 (IL-17), one of the key mediators in the pathogenesis of psoriasis. In addition to ixekizumab, another IL-17 blocker, secukinumab (Costentyx—Novartis), was approved last year for management of this disease.Psoriasis overviewAn estimated 7.5 million Americans have psoriasis. This autoimmune disorder occurs more frequently in patients who have a family history of the disease, with plaque psoriasis being the most common form. Plaque psoriasis is characterized by the development of thick, red skin with flaky, sliver-white plaques that can cause itching, scaling, and pain. Many patients also suffer from various comorbidities (e.g., cardiovascular disease) and lower related quality of life because of the impact of the disease on their social life and work productivity.For patients with a mild form of psoriasis, topical medications and phototherapy may be optimal treatments. However, for those with moderate to severe disease, systemic therapies are needed that may include methotrexate, cyclosporine, and/or acitretin. With these conventional treatments, some patients may experience loss of efficacy, adverse reactions, or an insufficient response.Supporting dataApproval was based on data from three double-blind, multicenter, Phase III studies—UNCOVER-1, UNCOVER-2 and UNCOVER-3—that evaluated the safety and efficacy of ixekizumab 80 mg every 2 weeks, following a 160-mg starting dose, in patients with moderate to severe plaque psoriasis. A total of 3,866 adult patients with plaque psoriasis covering a minimum body surface area of 10%, and who were candidates for systemic therapy on the basis of severity, were included in the trials. All three studies compared the efficacy and safety of ixekizumab with placebo after 12 weeks, and two of the studies included an additional comparator arm in which patients received etanercept (Enbrel—Amgen) 50 mg twice a week for 12 weeks. In addition, two of the studies also evaluated response rates with use of ixekizumab during a maintenance period through 60 weeks.In these studies, the coprimary efficacy endpoints at 12 weeks were a 75% improvement in the composite Psoriasis Area and Severity Index score ([PASI] 75), as well as a static Physician’s Global Assessment (sPGA) score of 0 or 1 and at least a 2-point improvement from baseline. Across all three studies, 87% to 90% of patients treated with ixekizumab had a significant improvement in their psoriasis plaques (PASI 75), and 81% to 83% of patients treated with ixekizumab achieved an sPGA score of 0 or 1. Placebo-treated patients had minimal responses, with 7% or fewer achieving a PASI 75 and a sPGA 0 or 1. For those who responded to ixekizumab, 75% consistently maintained that response at the 60-week endpoint during the two trials that assessed long-term use.Patient counselingGive patients the FDA-approved Medication Guide and educate them on proper dosage and administration. Train them in subcutaneous injection technique and tell them to administer each injection at a different location than the previous injection site. Patients should also be well aware of potential adverse events, such as increased risk of infections, hypersensitivity reactions, injection site reactions, and select gastrointestinal events.Ixekizumab (Taltz)Manufacturer: Eli LillyDrug class: Interleukin-17A antagonistIndication: Treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapyDosage: 160 mg at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks thereafterOf note: The drug is contraindicated in those with a previous serious hypersensitivity reaction to the agent. Warnings and precautions include increased risk of infection, potential for serious allergic reactions, and exacerbations of inflammatory bowel diseases.Injection site reactions, upper respiratory tract infections, nausea, and tinea infections were the most common adverse reactions associated with use of ixekizumab.Clinical pearlsBefore treatment with ixekizumab is initiated, all patients should be evaluated for tuberculosis (TB), as therapy should not be administered to those with active TB infection. In addition, patients should know that upper respiratory tract infections, oral candidiasis, conjunctivitis, and tinea infections occurred more frequently in those treated with ixekizumab than in those receiving a placebo. Administration of live vaccines should also be avoided in patients receiving ixekizumab. According to the manufacturer, the product will be available in the United States in the second quarter of 2016. A new treatment for plaque psoriasis, ixekizumab (Taltz—Eli Lilly), was recently approved for adults with moderate to severe disease. This agent targets interleukin-17 (IL-17), one of the key mediators in the pathogenesis of psoriasis. In addition to ixekizumab, another IL-17 blocker, secukinumab (Costentyx—Novartis), was approved last year for management of this disease. Psoriasis overviewAn estimated 7.5 million Americans have psoriasis. This autoimmune disorder occurs more frequently in patients who have a family history of the disease, with plaque psoriasis being the most common form. Plaque psoriasis is characterized by the development of thick, red skin with flaky, sliver-white plaques that can cause itching, scaling, and pain. Many patients also suffer from various comorbidities (e.g., cardiovascular disease) and lower related quality of life because of the impact of the disease on their social life and work productivity.For patients with a mild form of psoriasis, topical medications and phototherapy may be optimal treatments. However, for those with moderate to severe disease, systemic therapies are needed that may include methotrexate, cyclosporine, and/or acitretin. With these conventional treatments, some patients may experience loss of efficacy, adverse reactions, or an insufficient response. An estimated 7.5 million Americans have psoriasis. This autoimmune disorder occurs more frequently in patients who have a family history of the disease, with plaque psoriasis being the most common form. Plaque psoriasis is characterized by the development of thick, red skin with flaky, sliver-white plaques that can cause itching, scaling, and pain. Many patients also suffer from various comorbidities (e.g., cardiovascular disease) and lower related quality of life because of the impact of the disease on their social life and work productivity. For patients with a mild form of psoriasis, topical medications and phototherapy may be optimal treatments. However, for those with moderate to severe disease, systemic therapies are needed that may include methotrexate, cyclosporine, and/or acitretin. With these conventional treatments, some patients may experience loss of efficacy, adverse reactions, or an insufficient response. Supporting dataApproval was based on data from three double-blind, multicenter, Phase III studies—UNCOVER-1, UNCOVER-2 and UNCOVER-3—that evaluated the safety and efficacy of ixekizumab 80 mg every 2 weeks, following a 160-mg starting dose, in patients with moderate to severe plaque psoriasis. A total of 3,866 adult patients with plaque psoriasis covering a minimum body surface area of 10%, and who were candidates for systemic therapy on the basis of severity, were included in the trials. All three studies compared the efficacy and safety of ixekizumab with placebo after 12 weeks, and two of the studies included an additional comparator arm in which patients received etanercept (Enbrel—Amgen) 50 mg twice a week for 12 weeks. In addition, two of the studies also evaluated response rates with use of ixekizumab during a maintenance period through 60 weeks.In these studies, the coprimary efficacy endpoints at 12 weeks were a 75% improvement in the composite Psoriasis Area and Severity Index score ([PASI] 75), as well as a static Physician’s Global Assessment (sPGA) score of 0 or 1 and at least a 2-point improvement from baseline. Across all three studies, 87% to 90% of patients treated with ixekizumab had a significant improvement in their psoriasis plaques (PASI 75), and 81% to 83% of patients treated with ixekizumab achieved an sPGA score of 0 or 1. Placebo-treated patients had minimal responses, with 7% or fewer achieving a PASI 75 and a sPGA 0 or 1. For those who responded to ixekizumab, 75% consistently maintained that response at the 60-week endpoint during the two trials that assessed long-term use.Patient counselingGive patients the FDA-approved Medication Guide and educate them on proper dosage and administration. Train them in subcutaneous injection technique and tell them to administer each injection at a different location than the previous injection site. Patients should also be well aware of potential adverse events, such as increased risk of infections, hypersensitivity reactions, injection site reactions, and select gastrointestinal events.Ixekizumab (Taltz)Manufacturer: Eli LillyDrug class: Interleukin-17A antagonistIndication: Treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapyDosage: 160 mg at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks thereafterOf note: The drug is contraindicated in those with a previous serious hypersensitivity reaction to the agent. Warnings and precautions include increased risk of infection, potential for serious allergic reactions, and exacerbations of inflammatory bowel diseases.Injection site reactions, upper respiratory tract infections, nausea, and tinea infections were the most common adverse reactions associated with use of ixekizumab. Approval was based on data from three double-blind, multicenter, Phase III studies—UNCOVER-1, UNCOVER-2 and UNCOVER-3—that evaluated the safety and efficacy of ixekizumab 80 mg every 2 weeks, following a 160-mg starting dose, in patients with moderate to severe plaque psoriasis. A total of 3,866 adult patients with plaque psoriasis covering a minimum body surface area of 10%, and who were candidates for systemic therapy on the basis of severity, were included in the trials. All three studies compared the efficacy and safety of ixekizumab with placebo after 12 weeks, and two of the studies included an additional comparator arm in which patients received etanercept (Enbrel—Amgen) 50 mg twice a week for 12 weeks. In addition, two of the studies also evaluated response rates with use of ixekizumab during a maintenance period through 60 weeks. In these studies, the coprimary efficacy endpoints at 12 weeks were a 75% improvement in the composite Psoriasis Area and Severity Index score ([PASI] 75), as well as a static Physician’s Global Assessment (sPGA) score of 0 or 1 and at least a 2-point improvement from baseline. Across all three studies, 87% to 90% of patients treated with ixekizumab had a significant improvement in their psoriasis plaques (PASI 75), and 81% to 83% of patients treated with ixekizumab achieved an sPGA score of 0 or 1. Placebo-treated patients had minimal responses, with 7% or fewer achieving a PASI 75 and a sPGA 0 or 1. For those who responded to ixekizumab, 75% consistently maintained that response at the 60-week endpoint during the two trials that assessed long-term use. Patient counselingGive patients the FDA-approved Medication Guide and educate them on proper dosage and administration. Train them in subcutaneous injection technique and tell them to administer each injection at a different location than the previous injection site. Patients should also be well aware of potential adverse events, such as increased risk of infections, hypersensitivity reactions, injection site reactions, and select gastrointestinal events. Patient counselingGive patients the FDA-approved Medication Guide and educate them on proper dosage and administration. Train them in subcutaneous injection technique and tell them to administer each injection at a different location than the previous injection site. Patients should also be well aware of potential adverse events, such as increased risk of infections, hypersensitivity reactions, injection site reactions, and select gastrointestinal events. Patient counselingGive patients the FDA-approved Medication Guide and educate them on proper dosage and administration. Train them in subcutaneous injection technique and tell them to administer each injection at a different location than the previous injection site. Patients should also be well aware of potential adverse events, such as increased risk of infections, hypersensitivity reactions, injection site reactions, and select gastrointestinal events. Give patients the FDA-approved Medication Guide and educate them on proper dosage and administration. Train them in subcutaneous injection technique and tell them to administer each injection at a different location than the previous injection site. Patients should also be well aware of potential adverse events, such as increased risk of infections, hypersensitivity reactions, injection site reactions, and select gastrointestinal events. Ixekizumab (Taltz)Manufacturer: Eli LillyDrug class: Interleukin-17A antagonistIndication: Treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapyDosage: 160 mg at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks thereafterOf note: The drug is contraindicated in those with a previous serious hypersensitivity reaction to the agent. Warnings and precautions include increased risk of infection, potential for serious allergic reactions, and exacerbations of inflammatory bowel diseases. Ixekizumab (Taltz)Manufacturer: Eli LillyDrug class: Interleukin-17A antagonistIndication: Treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapyDosage: 160 mg at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks thereafterOf note: The drug is contraindicated in those with a previous serious hypersensitivity reaction to the agent. Warnings and precautions include increased risk of infection, potential for serious allergic reactions, and exacerbations of inflammatory bowel diseases. Ixekizumab (Taltz)Manufacturer: Eli LillyDrug class: Interleukin-17A antagonistIndication: Treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapyDosage: 160 mg at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks thereafterOf note: The drug is contraindicated in those with a previous serious hypersensitivity reaction to the agent. Warnings and precautions include increased risk of infection, potential for serious allergic reactions, and exacerbations of inflammatory bowel diseases. Manufacturer: Eli Lilly Drug class: Interleukin-17A antagonist Indication: Treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy Dosage: 160 mg at week 0, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks thereafter Of note: The drug is contraindicated in those with a previous serious hypersensitivity reaction to the agent. Warnings and precautions include increased risk of infection, potential for serious allergic reactions, and exacerbations of inflammatory bowel diseases. Injection site reactions, upper respiratory tract infections, nausea, and tinea infections were the most common adverse reactions associated with use of ixekizumab. Clinical pearlsBefore treatment with ixekizumab is initiated, all patients should be evaluated for tuberculosis (TB), as therapy should not be administered to those with active TB infection. In addition, patients should know that upper respiratory tract infections, oral candidiasis, conjunctivitis, and tinea infections occurred more frequently in those treated with ixekizumab than in those receiving a placebo. Administration of live vaccines should also be avoided in patients receiving ixekizumab. According to the manufacturer, the product will be available in the United States in the second quarter of 2016. Before treatment with ixekizumab is initiated, all patients should be evaluated for tuberculosis (TB), as therapy should not be administered to those with active TB infection. In addition, patients should know that upper respiratory tract infections, oral candidiasis, conjunctivitis, and tinea infections occurred more frequently in those treated with ixekizumab than in those receiving a placebo. Administration of live vaccines should also be avoided in patients receiving ixekizumab. According to the manufacturer, the product will be available in the United States in the second quarter of 2016.