By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Medical Director, Pharmacy, Northern California Kaiser Permanente, and Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The FDA has approved a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody directed against interleukin-17A (IL-17A). IL-17A has been identified as a key cytokine involved in the pathogenesis of psoriasis and psoriatic arthritis. Ixekizumab is the second IL-17A antagonist to be approved (secukinumab). It is marketed as Taltz.
INDICATIONS
Ixekizumab is indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.1
DOSAGE
The recommended dose is 160 mg initially, followed by 80 mg at week two, four, six, eight, 10, and 12, then every four weeks.1 The drug can be self-administered by subcutaneous injection. Recommended injection sites are abdomen, thigh, or back of arm. Ixekizumab is available as a 80 mg/mL single-dose prefilled autoinjector or prefilled syringe.
POTENTIAL ADVANTAGES
Ixekizumab appears to be more effective than etanercept.2
POTENTIAL DISADVANTAGES
The most frequent adverse event is injection site reactions (17%).1 As with other biologic drugs affecting the immune system, the risk of infections may be increased. Patients should be evaluated for tuberculosis prior to starting treatment.
COMMENTS
The efficacy of ixekizumab was evaluated in three randomized, double-blind, placebo-controlled trials.1,2 Subjects were ≥ 18 years of age presenting with plaque psoriasis involving a minimum body surface involvement of 10% and a static Physician Global Assessment (sPGA) score of ≥ 3 in overall assessment, and a Psoriasis Area and Severity Index (PASI) score ≥ 12, and were candidates for phototherapy or systemic therapy. Coprimary endpoints were a 75% improvement in PASI (PASI75) and sPGA of “0” (clear) or “1” (minimal) and at least a 2-point improvement from baseline. For those randomized to ixekizumab, the percent achieving sPGA of “0” or “1” ranged from 81-83% across the three studies, with placebo ranging from 2-7%. The percent achieving PASI75 ranged from 87-90%, compared to 2-7% for placebo.
In two studies, subjects were also randomized to etanercept (50 mg twice weekly).1,2 The response for etanercept response ranged from 36-53% for the coprimary endpoints.2 For treatment responders on ixekizumab at week 12, 75% of patients randomized to the maintenance dose of 80 mg every four weeks maintained their response compared to 7% randomized to placebo at week 60.1 For responders randomized to discontinue ixekizumab, the median time to relapse was 164 days. In this population, 66% regained their response within 12 weeks when the drug was restarted. There are no published studies comparing ixekizumab and secukinumab.
When comparing across placebo-controlled studies, the placebo-subtracted response rates for ixekizumab ranged from 80-88% for PASI75. For secukinumab, rates ranged 71-84% for PASI75.3 The study populations demonstrated similar PASI baseline scores — a median of 20 for secukinumab and 17-18 for ixekizumab. The studies used different five-point physician/investigator scales to assess disease severity.
CLINICAL IMPLICATIONS
Psoriasis is an inherited systemic inflammatory disease related to immune dysfunction. Ixekizumab is the second in the class monoclonal antibody to IL-17A, which is regarded as an important cytokine in the pathogenesis of psoriasis.4 Ixekizumab appears to be an effective drug, but how it compares to secukinumab in term of efficacy remains to be determined. The cost for ixekizumab is $4,104 for a two-week supply.
REFERENCES
-
Taltz Prescribing Information. Eli Lilly and Company. March 2016.
-
Griffiths CE, Reich K, Lebwohl M, et al. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): Results from two phase 3 randomised trials. Lancet 2015;386:541-551.
-
Cosentyx Prescribing Information. Novartis. January 2016.
-
Isailovic N, Daigo K, Mantovani A, et al. Interleukin-17 and innate immunity in infections and chronic inflammation. J Autoimmun 2015;60:1-11.
