At his session, “Psoriasis: Biologics,” presented at the AAD annual meeting 2022, Jashin J Wu, MD, FAAD, presented updates and what’s down the pipeline for biologics used to treat psoriasis.

His lecture focused on 3 major points:

• IL-17 inhibitor update;
• IL-23 inhibitor update; and
• Precision medicine in psoriasis.

For the IL-17 updates, Dr Wu started with secukinumab—a recombinant, high-affinity, fully human immunoglobulin G1κ monoclonal antibody that selectively binds and neutralizes IL-17A. He highlighted that the recommended dose is 300 mg via subcutaneous injection during weeks 0, 1, 2, 3, and 4 with a follow-up of 300 mg every 4 weeks. He stressed that physicians should screen for tuberculosis, and to use caution when prescribing to patients with active inflammatory bowel disease as flares could occur.

Next was ixekizumab which is a humanized IgG4 monoclonal antibody that neutralizes IL‑17A (IL-17) which was approved on March 22, 2016, for moderate-to-severe plaque psoriasis, and was approved for psoriatic arthritis (PSA). Dr Wu shared that the recommended dose is 160 mg with 80 mg injections distributed twice at week 0. This is followed by another 80 mg at weeks 2, 4, 6, 8, 10, and 12 with a transition to 80 mg every 4 weeks.

He then presented brodalumab, a human anti–interleukin-17 receptor A monoclonal antibody approved for moderate to severe plaque psoriasis. While the recommended dose is 210 mg at weeks 0, 1, and 2 followed by 210 mg every 2 weeks, Dr Wu stressed there was a contraindication regarding crohn’s disease in which there’s no warning on ulcerative colitis. He also noted that there was a box warning for suicidal ideation and behavior (SIB); therefore, brodalumab is only available through a restricted program, namely the Risk Evaluation and Mitigation Strategy (REMS), which requires:

• Prescribers be certified within the program and counsel patients about SIB risk
• Patients sign a Patient-Prescriber Agreement Form and are aware of the risk for SIB
• Pharmacies be certified with the program

The final IL-17 biologic Dr Wu introduced was bimekizumab.

“What's really exciting, to me, is bimekizumab. Bimekizumab is an upcoming interleukin-17A and 17F inhibitor,” Dr Wu stated. “It's had some recent data where it went head-to-head against secukinumab up to week 48, and it's been shown that it's effective.”

“More effective than secukinumab in pretty much all time points in terms of PASI 100, PASI 90, and PASI 75,” he continued.

Dr Wu then transitioned into updates on IL-23 inhibitors starting with guselkumab. Guselkumab is a human monoclonal antibody against IL-23 that was approved for adults with moderate-to-severe plaque psoriasis who are already candidates for systemic therapy or phototherapy psoriasis.

Next was tildrakizumab, a humanized antibody targeting IL-23 approved for moderate-to-severe plaque psoriasis with a recommended dose of 100 mg at week 0, week 4 and then every 12 weeks. This is given by a health care professional via 100 mg/mL in a single-dose prefilled syringe.

Dr Wu proceeded to risankizumab, a humanized monoclonal antibody targeting IL-23 that was approved for moderate-to-severe psoriasis.

“It has some really nice data that shows that it is very effective for psoriatic arthritis as well,” Dr Wu stated referencing risankizumab’s recent approval for treating PsA announced January 21, 2022. It has a recommended dose at 150 mg at week 0, week 4 and then every 12 weeks via a single-dose prefilled syringe or pen.

Concluding the IL-23 updates, Dr Wu brought up the question, “11 biologics and 4 oral meds- which to pick?”

“Well, IL-23 inhibitors are my first-line biologics for those 70% without psoriatic arthritis,” Dr Wu shared. “IL-17 inhibitors, certolizumab, or adalimumab are my first-line biologics for those 30% with psoriatic arthritis,” he added.

He also noted that, when it comes to utilization, IL-23 inhibitors should be prioritized over IL-17 inhibitors due to dosing and fewer AEs such as candida infections and IBD. However, if quicker clearance of psoriasis needed, and there is PsA together with psoriasis, then IL-17 inhibitors should be prioritized over IL-23 inhibitors.

Finally, Dr Wu touched upon his final topic point: precision in medicine. He stated that the current psoriasis biologics paradigm is broken noting that when physicians have no predictive tool to select appropriate treatment with patients who are not responding optimally to therapeutics, this inevitably leads to frustrated patients. The payer is also affected when they often pay for wrong biologic that then must be switched especially when they had the desires to initially pay for least costly, efficacious biologic. All of this inevitably leads to suboptimal outcomes where patients don’t clear, and there’s a delay in meeting patient expectations; therefore, playing a part in negatively impacting patients’ quality of life.

How to counter this? Dr Wu introduced Mind.Px™ which deals with correlating RNA to drug response. This is the missing predictive link between a patient’s genetic markers and response to different drug classes. It prospectively predicts individual patient response to TNFa, IL-17 and IL-23 inhibitors.

“Precision medicine tests will take the guesswork out of picking the first biologic,” he concluded.

Reference
Wu J. Psoriasis: biologics. Presented at: AAD Annual Meeting; March 25-28, 2022; Boston, MA.