Strategies for Systemic Therapy for Moderate to Severe Psoriasis

“When we get into groups, it’s always really powerful because we can look at and talk about objective data,” said Andrew Mastro, MS, PA-C, during a recent Dermatology Times Case-Based Roundtable event in Chicago, Illinois.

Mastro, a physician assistant at Illinois Dermatology Institute, moderated the roundtable discussion by presenting 3 complex cases of moderate to severe psoriasis to fellow colleagues to discuss treatment decisions.

Case 1

A 36-year-old man presented with a 6-month history of plaque psoriasis involving the scalp, arms, and lower legs, affecting approximately 10% body surface area (BSA), with moderate pruritus. Despite prior use of triamcinolone 0.1% cream and clobetasol shampoo prescribed by his primary care provider, he reported minimal improvement and ongoing impact on self-confidence and work performance. Given his busy schedule as a landscaper, frequent sun exposure, and desire for rapid and sustained clearance, the dermatology clinician initiated bimekizumab (Bimzelx; UCB), an IL-17 inhibitor, for convenient maintenance dosing every 8 weeks and potential for faster skin improvement compared with traditional topical or systemic therapies.

“Among biologics, IL-17s are definitely the fastest,” said an attendee.

Another attendee countered with: “I think the reason why some of the IL-17s on the market aren’t as durable as the IL-23s is because there are so many more IL-17 sectors than there are in IL-23.”

With the first case, Mastro presented data from the BE RADIANT study (NCT03536884) where adults with moderate to severe plaque psoriasis (PASI ≥12, BSA ≥10%, IGA ≥3) were randomly assigned 1:1 to receive bimekizumab, 320 mg, every 4 weeks or secukinumab (Cosentyx; Novartis), 300 mg, weekly for 4 weeks followed by once every 4 weeks.¹

At week 16, patients receiving bimekizumab were re-randomized 1:2 to continue every 4 weeks dosing or switch to every 8 weeks. The most common adverse events for both treatment groups were upper respiratory tract infection, oral candidiasis, and urinary tract infection. Overall, 61.7% of patients receiving bimekizumab320 mg every 4 weeks achieved PASI 100 by week 16 compared with 48.9% of patients receiving secukinumab300 mg every 4 weeks.¹

As one attendee mentioned, patients oftentimes come in with expectations that a biologic will clear their psoriasis in 2-3 weeks. Many of the attendees pointed out that it is crucial to set realistic expectations with patients started biologics and that they won’t necessarily have the speed of high-potency topical steroids, but biologics will work longer and better over time.

“This case presented a great example of when speed and efficacy must meet in order to satisfy the patients' needs. This taught the group how to approach a patient who is caught in a treatment cycle with little benefit, and how to approach the psychosocial end. We also discussed the mechanistic differences with the IL-17 class, and teasing out the IL17A/F vs just A,” Mastro said.

Case 2

A 41-year-old man with longstanding plaque psoriasis presented with worsening plaques involving approximately 8% BSA on the arms and legs, along with new-onset nail pitting and onycholysis. He had been treated with ustekinumab (Stelara; Janssen) for 2 years, achieving initial skin clearance before losing response. Persistent nail involvement and diminishing efficacy led to frustration, as his symptoms interfered with work-related typing and piano playing. After reviewing available biologic options, the dermatology clinician transitioned therapy to risankizumab (Skyrizi; AbbVie), an IL-23 inhibitor, for its potential to improve both skin and nail disease and provide convenient 12-week maintenance dosing.

For the group discussion, Mastro discussed the UltIMMA-1 (NCT02684370) and UltIMMA-2 (NCT02684357) studies, which included adults with moderate to severe plaque psoriasis who were randomly assigned 3:1:1 to receive risankizumab, 150 mg, ustekinumab, 45 mg or 90 mg, or placebo. After 16 weeks, patients assigned to placebo switched to risankizumab, 150 mg. As Mastro noted, results from UltIMMA-2 were similar to UltIMMA-1. The most frequently reported adverse events were upper respiratory infection, urinary tract infection, influenza, and headache. By week 16, 36% of patients receiving risankizumab achieved PASI 100 compared with 12% of patients receiving ustekinumab. By week 52, 56% of patients receiving risankizumab achieved PASI 100 compared with 21% of patients receiving ustekinumab.²

“This case presents a great example of a high-impact area like the nails, and how much of a burden this can be for our patients. This also presents an opportunity for us to advance their therapy to a biologic, recognizing that the changes in the nails likely require it. The concept of flare vs failure is a take home point, which can be hard to differentiate. However, the discussion on differences with IL-23 and IL-17 was key, especially the idea that IL-23 is the class with durability, which I think was challenged with what we discussed for bimekizumab,” Mastro said.

Case 3

A 47-year-old woman with a 10-year history of plaque psoriasis involving approximately 5% BSA, primarily on the scalp and elbows, presented with persistent pruritus and discomfort localized to the scalp. Despite adherence to secukinumab therapy for 18 months, she experienced only partial improvement on the elbows and minimal response on the scalp. The patient expressed dissatisfaction with her disease control and reported being self-conscious about visible scalp plaques. She also noted joint stiffness, which she attributed to aging but warranted further evaluation for psoriatic arthritis (PsA).

Following assessment and a discussion, secukinumab was discontinued and bimekizumab 320 mg was initiated. The decision was based on evidence demonstrating superior efficacy of dual IL-17A and IL-17F inhibition in achieving high levels of skin clearance, including in difficult-to-treat areas such as the scalp. The patient was referred to a rheumatologist for PsA workup and will be monitored for skin response and symptom improvement over the next 12 to 16 weeks.

“I have a patient who has failed 2 different IL-17s. I just started her on an IL-17A/F inhibitor and she said after her visit check-in that her hands don’t hurt anymore, related to her psoriatic arthritis,” said one attendee.

Mastro reviewed pooled data from the BE RIGHT (NCT03598790) and BE RADIANT (NCT03536884) open-label extension (OLE) studies which analyzed by patient subgroups, including patients with self-reported PsA signs/symptoms (PASE ≥ 47); patients with significant nail involvement (mNAPSI > 10); patients with moderate or severe scalp involvement (scalp IGA ≥ 3); and patients with 3 or more risk factors for PsA.³

During the OLEs, 75.7% of patients receiving bimekizumab achieved PASI 100 by week 48, 73.6% by week 96, and 70.2% by week 144.³

“This case provided a great example of another high impact/low BSA example, which can be difficult on the documentation end, but also whether we approach the biologic convo 2/2 to the stigma of only being for high BSA patients. The larger take home point was the concept of PsA and how we approached, graded, asked questions, and referred to rheumatology. Here we also dug a lot into the safety of the IL-17 class, which is critical from our patient narrative side but also how we look at them relative to the other classes of biologics,” Mastro said.

Final Thoughts

Mastro highlighted the value of observing how expert dermatology clinicians frame patient discussions when considering advanced psoriasis therapies. He noted that while much of the dialogue focused on familiar themes—safety considerations, class selection, and patient communication—the nuanced perspectives shared during the IL-23 vs IL-17 discussion offered particularly engaging clinical insights, even if not entirely new.

“The value of Case-Based Roundtables is huge. The setting allows for a free-flowing, stress-free conversation on best practices, preferences, and open-form Q/A. When a great case is the basis of discussion, it’s not just the science that can be explored, but the nuance of our patient conversation. We can learn the science anywhere; it’s having the time to truly discuss how we talk about these concepts with patients is what’s unique. What you learn in a setting like this is far stickier than a didactic lecture,” Mastro concluded.

References

1. Reich K, Warren RB, Lebwohl M, et al. Bimekizumab versus secukinumab in plaque psoriasis. N Engl J Med. 2021;385(2):142-152. doi: 10.1056/NEJMoa2102383
2. Gordon KB, Strober B, Lebwohl M, et al. Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo-controlled and ustekinumab-controlled phase 3 trials. Lancet. 2018;392(10148):650-661. doi: 10.1016/S0140-6736(18)31713-6
3. Gisondi P, Merola J, Thaci D, et al. Bimekizumab efficacy in patients with psoriasis and risk factors for psoriatic arthritis: 3‑year results from 5 phase 3/3b studies. Poster presented at: International Congress of Dermatology. June 18-21, 2025. Rome, Italy.