WASHINGTON — Beyond clinical experience and judgment, few clear principles have emerged to help clinicians navigate the still-growing maze of biologic agents for psoriasis, according to a review presented here.
Depending on how efficacy is defined, all of the approved biologic agents are effective, and safety also is similar, as serious adverse events are uncommon with the drugs, said George Han, MD, PhD, of Mount Sinai Beth Israel Hospital in New York City, at the American Academy of Dermatology (AAD) meeting. All of the drugs have activity against psoriasis in problematic body areas, such as the scalp and hands.
Clinical trial results offer little guidance to clinical practitioners, said Han. The most widely used instrument for assessing efficacy is the Psoriasis Area and Severity Index (PASI), which is essentially a research tool.
“Who in here has sat down and done a PASI score on their patients in the clinic?” he asked, as he scanned the AAD audience for raised hands. “For the vast majority of us, we don’t use PASI, because you literally have to take out pen and paper, do a worksheet, start doing the math and things we’ve tried to forget from elementary school. In practice, we usually just look at the patient and do more of a global assessment.”
To illustrate the point, Han displayed side-by-side photos of two different patients, before and after treatment. By visual inspection, the two patients had similar baseline disease status, and both patients had substantial clearance of psoriasis after treatment, with only minor differences by observation. The patients’ baseline PASI scores differed by about 20%. At the post-treatment assessment, one patient had a PASI score of 1.5 and the other had a PASI score of 4.0 — a 150% difference.
Evolving PASI Data
For years, 75% improvement in baseline PASI status (PASI75) represented the standard definition for response to treatment. Older drugs achieve PASI 75 in about half of patients. Newer biologic agents achieve that level of improvement in a higher proportion of patients, reaching 80%-90% in some studies.
However, even patients who do not achieve a PASI75 response might derive substantial benefit from treatment. As an example, Han showed photos of patients whose treatment outcome was expressed as the mean change PASI score. Treated with etanercept (Enbrel), the patient had a 70% mean change in PASI score from baseline.
“This is an average patient on the ‘dud’ of our biologics, and it’s still pretty darn good,” said Han. “In reality, I think we’re talking about fairly minor differences between drugs.”
Newer biologic agents have set the response bar higher. As many as 80% of patients treated with newer biologics attain PASI90 and half achieve PASI100, said Han. To date, limited comparative data have emerged to help gauge the relative efficacy of the newer agents.
Biologics differ with respect to speed of improvement. Tumor necrosis factor (TNF) inhibitors work “pretty fast,” but drugs that target interleukin (IL)-17 work the fastest, providing noticeable improvement within a week or two. In contrast, drugs that work through the IL-12/IL-23 pathway take a little longer to reach peak efficacy, said Han.
Examination of the safety profiles of biologic drugs offers little guidance in drug selection. Infection often is cited as a risk of biologic therapy, but Han said, “How much of that is real and how much of it is theoretical? If you look at most of the trials, rates of upper respiratory infections are not that far off from placebo.”
No signal related to cardiovascular risk has emerged, he continued. Concern about a potential risk of inflammatory bowel disease (IBD) with drugs that inhibit interleukin (IL)-17 and IL-23 has turned out to be theoretical.
With respect to malignancy, a small but real risk of nonmelanoma skin cancer associated with inhibitors of tumor necrosis factor-alpha is emerging, said Han. Such associations take a long time to clarify, and data on the topic continue to accumulate.
The Arthritis Factor
One factor that does influence the choice of biologic agents is concurrent psoriatic arthritis (PsA), said Kristina Callis-Duffin, MD, of the University of Utah in Salt Lake City, in a separate AAD presentation. Not all biologic agents have approval for both psoriasis and PsA.
“If a patient has psoriatic arthritis, or has signs or symptoms of psoriatic arthritis, this changes the possibilities,” she said.
About 30% of patients with psoriasis also have PsA. Clinicians should evaluate every patient with psoriasis for PsA, as studies have shown that a delay in diagnosis of PsA of as little as 6 months is associated with worse long-term outcomes.
One logical approach would be the “two birds, one stone” strategy, said Callis-Duffin. Nine systemic/biologic agents have approval for both psoriasis and PsA:
- Apremilast (Otezla)
- Etanercept (Enbrel)
- adalimumab (Humira)
- Infliximab (Remicade)
- Certolizumab pegol (Cimzia)
- Secukinumab (Cosentyx)
- Ixekizumab (Taltz)
- Ustekinumab (Stelara)
Tofacitinib (Xeljanz) and golimumab (Simponi) have approval for PsA but not psoriasis.
The American College of Rheumatology (ACR) and National Psoriasis Foundation (NSF) recommend TNF inhibitors as first- and second-line therapy for PsA. However, in a recent randomized trial of patients with PsA, ixekizumab (an IL-17A antagonist) led to significantly higher rates of joint and skin improvement as compared with the TNF inhibitor adalimumab, Callis-Duffin noted.
PsA with axial disease is once exception to the TNF inhibitor-first approach, she continued. The ACR/NSF guideline recommends an initial trial of nonsteroidal anti-inflammatory drugs and physical therapy. If the condition does not improve, a TNF inhibitor is preferred, followed by an IL-17 inhibitor. Neither methotrexate nor IL-12/IL-23 inhibitors are recommended.
Several other exceptions elevate the status of IL-23 inhibition in PsA: patients with IBD, as ustekinumab has an indication for Crohn’s disease; psoriasis flare related to TNF inhibition; inadequate skin response to TNF inhibition; contraindications to TNF; and IL-17 inhibition.
Han disclosed relevant relationships with Celgene, Eli Lilly, Janssen, Pfizer, Regeneron, Sanofi, Sonoma Pharmaceuticals, and Sun Pharmaceuticals.
Callis-Duffin disclosed relevant relationships with AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and Sienna Biopharmaceuticals.