Back in 2003, in just its second installment, this column highlighted upcoming therapies for psoriasis, a relatively common chronic inflammatory skin disease characterized by red scaly plaques that can be accompanied by joint involvement. At that time, the only biologic medication approved for the condition was alefacept, sold as Amevive. Etanercept, marketed as Enbrel, was approved only for those with psoriatic arthritis, not for those whose psoriasis was limited to skin. Two other TNF inhibitors, adalimumab (Humira) and infliximab (Remicade), were being studied. The FDA was considering efalizumab (Raptiva), another biologic that was developed as a treatment for psoriasis. These drugs carried a yearly price tag of $16,000 to $20,000.
What a difference 13 years have made!
As it turned out, Raptiva and Amevive were abandoned and are no longer on the market. But other biologics have taken their place, and the menu of available agents and the mechanisms of action they use is growing. Also growing, and by leaps and bounds: the prices. They have more than doubled.
Human genome studies have uncovered a host of polymorphisms in numerous genes regulating the immune system. Those discoveries have led to the development of drugs targeting not just the legacy TNF pathway but also various interleukin pathways.
The interleukins, of course, are a family of cytokines, those swarms of messenger compounds that allow the various parts of the immune system to communicate. So far 36 different interleukins have been described. These remarkable proteins promote the differentiation of T and B lymphocytes and hematopoietic cells and influence numerous other pathways. They interact in an amazingly complex manner throughout the immune system. Teasing out their individual roles is almost as difficult as trying to isolate the sound of one instrument in the New York Philharmonic.
Ixekizumab, sold as Taltz, is the latest biologic to be approved. It is a humanized IgG4 monoclonal antibody that selectively binds with interleukin 17A and, in so doing, inhibits its interaction with the IL-17 receptor. It is hitting the market with three randomized, double-blind, multicenter phase 3 studies under its belt, two of which compared results against etanercept in treating psoriasis.
Taltz is indicated for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. It is delivered as a subcutaneous injection. Dosing starts with two 80-mg injections the first week, followed by 80-mg injections at Weeks 2, 4, 6, 8, 10, 12 and then an 80-mg injection every four weeks. This schedule makes it a bit more complicated to use than some of the competitors, at least for the first three months.
The agent comes as either a pre-filled syringe or an autoinjector and can be self-injected after proper training and with physician supervision.
Taltz is accompanied by a warning about an increased risk of infections including upper respiratory tract infections, oral candidiasis, conjunctivitis, and tinea (ringworm). It does not, however, have the black box warning common to many drugs used to treat autoimmune diseases. As is usual, patients should be evaluated for tuberculosis prior to and after initiating treatment, and Taltz is contraindicated in those with active tuberculosis who are not undergoing treatment.
During the clinical trials, serious hypersensitivity reactions included angioedema and urticaria (hives), but they were rare, each occurring no more than one-tenth of 1% of the time. Crohn’s disease and ulcerative colitis also occurred at a greater frequency in the Taltz group (0.1% and 0.2% respectively) than in patients assigned to the placebo group (0%).
Other adverse events included injection-site reactions (primarily pain and erythema), most of which did not lead to discontinuation of the drug. Neutropenia occurred in 11% of Taltz subjects compared with 3% treated with placebo, but it was not accompanied by an increase in infections. Thrombocytopenia also occurred, but almost all instances were grade 1.
Perhaps of more concern to those managing care and making coverage decisions might be the immunogenicity; 22% of subjects treated during the 60-week treatment period developed antibodies to Taltz. Those with higher antibody titers demonstrated decreased clinical response as well as decreased drug concentration. About 2% of subjects developed antibodies that were termed “neutralizing,” resulting in loss of efficacy. The manufacturer pointed out that the test for neutralizing antibodies has limitations, and this number may be misstated and comparison to other drugs may be misleading.
The three randomized studies of Taltz collectively enrolled 3,866 subjects 18 years of age or older with plaque psoriasis with a minimum body surface area involvement of 10%, a static Physician Global Assessment (sPGA) score of >3 in overall assessment of plaque thickness, induration, erythema and scaling (scale of 0–5) and a Psoriasis Area and Severity Index (PASI) score of >12. The trials assessed the changes from baseline to Week 12. The primary endpoints were a PASI score that was reduced by at least 75% and a sPGA score of 0 or 1, meaning total clearing or minimal involvement.
The combined result for 82% of patients was an sPGA score of 0 or 1, and about 88% demonstrated a PASI score of 75. More amazing was that about 70% achieved a PASI score of 90.
In short, this drug rocks!
Other drugs also demonstrate high efficacy but due to differences in selection criteria and study design it is virtually impossible to directly compare two different drugs for psoriasis (or any other disease for that matter) based on separate trials. This is where Taltz stands out because of the two pivotal trials that included an etanercept arm. Those two trials randomized subjects to a dosing schedule of either every two weeks or every four weeks for Taltz, placebo, or etanercept. Remember that the FDA approval for Taltz sets the dosage frequency at every four weeks after the initial period of more frequent injections.
In an article published in Lancet last year, Christopher E. M. Griffiths and his colleagues reviewed both of the head-to-head studies. They found that Taltz demonstrated greater efficacy than the placebo and etanercept over the 12-week study period. The comparison of the study subjects that experienced complete resolution is telling: 35% of those receiving Taltz every four weeks and 38% to 41% of those getting it every two weeks achieved complete resolution as compared with 5% to 7% of those receiving etanercept (p<0.0001). Obvious differences in response between Taltz and etanercept occurred as early as Week 1.
To be fair, the new drug does have a slight downside. Griffiths and company noted that overall infections occurred more frequently in patients taking Taltz than those randomized to receive etanercept or placebo. Twenty-six percent of those taking Taltz developed an infection compared with 22% in the etanercept group and 21% in the placebo group. However, the authors note that less than 1% of patients in all the treatment groups had serious infections and there were no notable differences among them.
Using the GoodRx app with Atlanta as the location, the monthly maintenance price of Taltz is about $4,200 per 80-mg syringe. That’s about 10% more expensive than the price that GoodRx had for etanercept.
While cost remains a challenge, things are changing fast in the treatment of psoriasis. The approval of Taltz suggests that the bar for treatment is getting set higher, so patients (and their doctors) may soon be expecting, if not complete remission, then something very close to it.