The availability of treatments like brodalumab and guselkumab in the u.S. in 2017, and the anticipated commercial availability of these agents in Canada, will broaden the therapeutic choices in the treatment of moderate-to-severe psoriasis.
Various data on the use of IL-17 inhibitors and IL-23 inhibitors were presented this fall in Geneva at the annual meeting of the european Association of Dermatology and Venereology (eADV).
Dr. Melinda Gooderham, dermatologist and medical director of the Skin Centre for Dermatology in Peterborough, ont., presented data at the eADV meeting regarding dosing of ixekizumab in patients with moderate-to-severe plaque psoriasis, showing every two-week dosing to be superior to every four-week dosing over 52 weeks.
Data on secukinumab, which targets IL-17A, were also presented at the eADV meeting and demonstrated that the biologic provided skin clearance in patients with moderate-tosevere plaque psoriasis at five years. Specifically, the majority of patients who achieved Psoriasis Area Severity Index (PASI) 90 and 100 maintained their response out to five years. Similar long-term data on the efficacy and safety of ixekizumab up to two years were presented.
These biologics that target the IL-17 pathway are offering great efficacy as well as robust safety, said Dr. Charles Lynde, director of the Lynde Institute for Dermatology in Markham, ont., and associate professor, Department of Medicine, university of Toronto.
Enhanced management of psoriasis
The remarkable efficacy of those agents is consistent with treat-to-target recommendations for psoriasis and psoriatic arthritis as developed by Canadian leaders in dermatology and rheumatology. Canadian dermatologists and rheumatologists published recommendations earlier this year on the enhanced management of the two chronic conditions in daily practice after conducting a needs assessment among Canadian physicians managing the diseases as well as a literature review on outcomes in clinical trials and practice (J Rheumatol 2017 Apr; 44(4):519– 534).
Adverse events such as Candida infections have been reported with the use of IL-17 inhibitors in patients being treated for psoriasis and psoriatic arthritis, when compared to patients treated with placebo or ustekinumab (Br J Dermatol 2017 Jul; 177(1):47–62).
Accordingly, it has been recommended that patients undergoing anti-IL-17 therapy be monitored for fungal infections and be appropriately managed if these infections occur, but it has not been recommended that patients discontinue IL-inhibition therapy because the Candida infections are mild-to-moderate and can be managed with standard therapy.
Recently, an extremely rare instance of psoriasiform eruption occurred with secukinumb therapy that involved the fingertips and nails but it was found to resolve with ustekinumab and topical methotrexate, underlining that other biologics can be considered when patients experience disease flares with another class of biologics (JAMA Dermatol 2017 Aug 2).
Brodalumab, which was evaluated in three, randomized, controlled clinical trials involving more than 4,300 patients, carries a black-box warning in the U.S. with regard to an observed risk for suicidal thoughts and actions.
Different mechanisms of action
Because brodalumab acts on the IL-17 receptor, it may prove to have a different impact than other IL-17 inhibitors like secukinumab and ixekizumab, explained Dr. David n. Adam, medical director, Baywood Dermatology, lead investigator, CCA Medical research, assistant professor, university of Toronto, active staff, St. Michael’s hospital in Toronto, and president, Dermatology Association of Ontario.
“The real question is if the different mechanism of action ends up making a difference in overall efficacy or duration of response,” said Dr. Adam. “If you have a sub-optimal response to a monoclonal antibody that targets soluble IL-17, would targeting the receptor improve that response? We know that brodalumab blocks signalling through all of the IL-17 cytokine family, A through F.”
The emerging therapies that selectively target IL-23, such as guselkumab, risankizumab, and tildrakizumab, are impressive in their efficacy and safety, said Dr. Lynde.
“It is good for Canadian dermatology and our patients to have all these options,” said Dr. Lynde.
“These new drugs can offer hope for people who have previously failed biologics.”
An emerging therapy like guselkumab may present an alternative to patients who do not experience success with ustekinumab. A randomized, double-blind, Phase III investigation found that patients who did not have an adequate response to ustekinumab by week 16 obtained benefit to being switched to 100 mg of guselkumab (Br J Dermatol 2017 Jun 21).
In addition, guselkumab may prove effective outside of the treatment of psoriasis. results from a Phase 2a study presented at the eADV meeting pointed to the positive and significant impact of guselkumab on joint symptoms, physical function, and psoriasis in patients who had active psoriatic arthritis with a minimum of 3% body surface area affected.
Other treatment options available
Traditional treatments for psoriasis remain viable choices. Phototherapy, for example, is a choice for patients who do not want to be exposed to any systemic treatment, said Dr. Catherine Zip, a dermatologist in Calgary and clinical associate professor at the university of Calgary.
“Some patients do not want to take anything internally,” said Dr. Zip. “For some patients, it’s great. It’s time-consuming, however, to come in for phototherapy treatment two or three times weekly for months.”
For pregnant women with extensive psoriasis, phototherapy is also the preferred treatment, said Dr. Zip. “narrow-band uVB is the treatment of choice for widespread psoriasis during pregnancy.”
In patients with milder cases of psoriasis, where less than 10% of the body surface area is affected, a therapy like apremilast is an appropriate option, noted Dr. Lynde. “There is a good niche for this drug,” he said.
Indeed, some of the advantages of apremilast include the fact that it does not require ongoing monitoring to evaluate for any organ toxicity, is administered orally, and produces weight loss (Am J Clin Dermatol 2017 Jun 8).
Despite all the novel therapies emerging to treat psoriasis, roadblocks to access may exist depending on the decisions of payers to reimburse the costs of the therapies, according to Dr. Lynde. “We do not know where biosimilars will fit [in clinical practice],” he said.
The integration of biosimilars into dermatology is not a uniquely Canadian challenge. The International Psoriasis Council has recommended that dermatologists take an active role in proposing prescribing policies vis-a-vis biosimilars in their respective jurisdictions (Br J Dermatol 2017 Jun 24).
Originally published in The Chronicle of Skin & Allergy (Oct./Nov. 2017;23(7):page 1, 4,6)