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Countdown to Clinical Knowledge of IL-17 Inhibitors in Psoriasis

  • Authors: Ulrich Mrowietz, MD; Laura Savage, MD
  • CPD Released: 9/16/2021
  • Valid for credit through: 9/16/2022, 11:59 PM EST
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Target Audience and Goal Statement

This educational activity is intended for an international audience of non-US dermatologists, pediatricians, and primary care physicians.

The goal of this activity is to relate data on interleukin (IL)-17 inhibitors to clinical practice and address broader issues in psoriasis (PsO) management, such as treatment goals and recommendations.

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • Benefit/risk profile for IL-17 inhibitors in PsO 
    • Key quality of life data for IL-17 inhibitors in psoriasis 


WebMD Global requires each individual who is in a position to control the content of one of its educational activities to disclose any relevant financial relationships occurring within the past 12 months that could create a conflict of interest.


  • Ulrich Mrowietz, MD

    Professor of Dermatology
    University Medical Center Schleswig-Holstein
    Kiel Campus, Germany


    Disclosure: Ulrich Mrowietz, MD, has the following relevant financial relationships:
    Advisor or consultant for: AbbVie; Aditxt; Almirall; Amgen; Aristea; Boehringer Ingelheim; Bristol Myers Squibb Company; Celgene; Dr. Reddy’s; Foamix; Formycon; Immunic; Janssen; LEO Pharma; Lilly; Medac; Novartis; Phi-Stone; Pierre Fabre; Sanofi-Aventis; UCB
    Speaker or a member of a speakers bureau for: AbbVie; Almirall; Amgen; Boehringer Ingelheim; Celgene; Foamix; Janssen; LEO Pharma; Lilly; Medac; Novartis; Sanofi-Aventis; UCB
    Grants for clinical research from: AbbVie; Almirall; Celgene; Janssen; Novartis; UCB


  • Laura Savage, MD

    Consultant Dermatologist
    Leeds Centre for Dermatology
    Honorary Senior Lecturer
    University of Leeds
    United Kingdom


    Disclosure: Laura Savage, MD, has the following relevant financial relationships:
    Advisor or consultant for: AbbVie; Almirall; Amgen; Biogen; Celgene; Janssen; LEO Pharma; Lilly; Merck Sharp & Dohme; Novartis; Pfizer; UCB
    Speaker or a member of a speakers bureau for: AbbVie; Almirall; Amgen; Biogen; Celgene; Janssen; LEO Pharma; Lilly; Merck Sharp & Dohme; Novartis; Pfizer; UCB
    Grants for clinical research from: Janssen; Pfizer


  • Alessia Piazza, PhD

    Medical Education Director, WebMD Global, LLC


    Disclosure: Alessia Piazza, PhD, has disclosed no relevant financial relationships.

  • Eloise Ballard, PhD

    Scientific Content Manager, WebMD Global, LLC


    Disclosure: Eloise Ballard, PhD, has disclosed no relevant financial relationships.

Content Reviewer

  • Stephanie Corder, ND, RN, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC


    Disclosure: Stephanie Corder, ND, RN, CHCP, has disclosed no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has disclosed no relevant financial relationships.

Accreditation Statements

    For Physicians

  • The Faculty of Pharmaceutical Medicine of the Royal Colleges of Physicians of the United Kingdom (FPM) has reviewed and approved the content of this educational activity and allocated it 0.25 continuing professional development credits (CPD).

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Countdown to Clinical Knowledge of IL-17 Inhibitors in Psoriasis

Authors: Ulrich Mrowietz, MD; Laura Savage, MDFaculty and Disclosures

CPD Released: 9/16/2021

Valid for credit through: 9/16/2022, 11:59 PM EST


Activity Transcript

Ulrich Mrowietz, MD: Hello, I'm Ulrich Mrowietz. I'm a professor of Dermatology at the Psoriasis Center at the Department of Dermatology at the University Medical Center Schleswig-Holstein, Kiel Campus. Welcome to this program, titled "Countdown to Clinical Knowledge of IL-17 Inhibitors in Psoriasis."

Joining me today is Laura Savage, who is a consultant dermatologist at the Leeds Center for Dermatology and an honorary senior lecturer at the University of Leeds in the UK. Welcome, Laura.

Laura Savage, MD: Hi, Ulrich.

Dr Mrowietz: This is a quickfire program and we'll have just 60, sometimes 90 seconds, to answer each question. So, let's start. Laura, which biologics, which different modes of actions, do we have for psoriasis patients?

Dr Savage: So, Ulrich, we now have 11 originator biologic agents, plus biosimilars, with a further agent, bimekizumab, to follow.

The first to be introduced were those drugs targeting tumor necrosis factor (TNF), which remain a highly cost-effective part of our treatment armamentarium now that we have biosimilars available. Now, these were followed by the introduction of ustekinumab, which was the first and still is the only agent to target the p40 subunit shared by interleukin (IL)-12 and -23.

Then more efficacious agents, such as risankizumab, guselkumab, and tildrakizumab were developed to solely target IL-23 through the p19 subunit to prevent the activation and maintenance of pathogenic Th17 cells. So, that's 3 classes of biologics. The remaining 3 classes all target the IL-17 family of cytokines in some form.

Okay. So, Ulrich, perhaps, I can ask you a question. Why are new biologics needed when we have so many already?

Dr Mrowietz: Well, as you all know, we no longer regard psoriasis as a skin disease. The term "psoriasis disease" reflects at least 3 major domains of the disease. This is skin inflammation, bone/joint inflammation normally referred to as arthritis, and vascular inflammation. In addition, we have independent risk factors causing additional inflammation, such as obesity.

So, to have beneficial effects on all 3 domains of psoriasis disease, we need more biologics that have been shown to have beneficial effects on all these 3 domains.

Dr Savage: I fully agree with you, Ulrich. We need to be trying to treat the patients in their entirety and not just seeing psoriasis as a single disease entity.

Dr Mrowietz: Yes. Laura, what can be achieved with approved IL-17 inhibitors in psoriasis in terms of efficacy? And you have 90 seconds to answer.

Dr Savage: Each of the currently licensed drugs targeting IL-17 -- that being secukinumab, ixekizumab and brodalumab -- were investigated in head-to-head phase 3 studies against ustekinumab, which was the most efficacious drug on the market at the time. And all with a Psoriasis Area and Severity Index (PASI) 90 endpoint, which had raised the bar from PASI 75 in previous trials. And PASI 90 was achieved in over three-quarters of patients in the CLEAR, IXORA-S, and AMAGINE-2 and -3 clinical trials. And their effects were rapid with improvement seen in as little as 2 to 4 weeks.

And superiority of ixekizumab has also been demonstrated over guselkumab in the IXORA-R study at 12 weeks with PASI 100. And I think it's great to see increasing numbers of active comparator trials between these top-line, highly efficacious agents.

And as mentioned beyond the trunk and limbs, primary endpoint trials for IL-17 inhibitors in the scalp, the nail, palmoplantar, and genital psoriasis have also shown a sustained high efficacy.

Dr Mrowietz: Now, moving on to emerging IL-17 inhibitors, what can be achieved in terms of efficacy with bimekizumab?

Dr Savage: Bimekizumab is different to secukinumab and ixekizumab in that it not only targets IL-17A but also the F isoform, which like IL-17A is a key driver of human chronic tissue inflammation.

And in the extensive bimekizumab phase 3 program, superiority is demonstrated over placebo, ustekinumab and adalimumab for PASI 90 at week 16 in the BE READY, BE VIVID, and BE SURE phase 3 clinical trials, respectively. And non-inferiority is demonstrated against secukinumab in BE RADIANT.

The goalposts of clinical trials, I think, look set to change again with outstanding PASI 100 responses reported for bimekizumab. By week 48, 46% of participants treated with secukinumab 300 mg, 4- weekly, achieved complete skin clearance compared with 67% of those receiving bimekizumab 8-weekly. So, that's almost a third more patients achieving PASI 100.

Dr Mrowietz: Well, that was a little bit more than 60 seconds. So, Laura, for the next question, you need to be very short but nevertheless, precise. Do these therapies also show efficacy in psoriatic arthritis as you have already mentioned?

Dr Savage: Yes, they do. So, both secukinumab and ixekizumab have a license for the management of psoriatic arthritis, and bimekizumab is in clinical trials. Secukinumab and ixekizumab demonstrated near identical American College of Rheumatology (ACR) 20 and 50 responses to adalimumab in the EXCEED and SPIRIT-H2H clinical trials, respectively, but with much greater skin clearance for patients treated with the IL-17A inhibitor. Bimekizumab has also demonstrated a high threshold disease control in a recent phase 2B study, BE ACTIVE, with over 50% of bimekizumab treated patients achieving ACR 50 up to 3 years in the open-label extension.

And of course, we must not limit our thinking to just peripheral psoriatic arthritis. In the MAXIMISE trial, both secukinumab 300 mg and 150 mg, which is the licensed psoriatic arthritis dose, provided significant improvement in signs and symptoms of axial disease compared to placebo in patients with axial psoriatic arthritis, with inadequate response to non-steroidal anti-inflammatory drugs.

Dr Mrowietz: Well, Laura, we just heard about the physicians' reported outcomes, such as a PASI and of course the rheumatology scores we are using, but what about patient-reported outcomes or quality of life data? What can we achieve with available and emerging IL-17 inhibitors?

Dr Savage: So, most data for quality of life relate to the Dermatology Life Quality Index (DLQI) responses and correlation analyses demonstrate how the mean reduction in DLQI usually correlates with the mean percentage reduction in PASI. In the CLEAR head-to-head clinical trial of secukinumab against ustekinumab, 73% of patients achieving PASI 90 achieved normalization of their quality of life measured by a DLQI of 0 or 1 compared with just 45% of those with a 75% to 89% reduction in their PASI score from baseline, which highlights the importance of aiming for clear or almost clear skin for our patients.

And similar findings have been shown outside of clinical trials and in real-world registries such as DERMBIO, which include patients treated with secukinumab and ixekizumab.

Now, we must be mindful, of course, that DLQI may not capture the full patient disease perspective. And for future trials, additional measures are needed.

In the phase 3 BE SURE clinical trial, the Psoriasis Symptoms and Impacts Measure (P-SIM) was used to evaluate patients with perceived pain, itching, and scaling. And a ≥ 4 point reduction from baseline in P-SIM is considered clinically meaningful and was achieved in 65 to 70% of patients treated with bimekizumab compared with 45% to 48% of patients treated with adalimumab at week 24.

Dr Mrowietz: Well, thank you, Laura, for this very comprehensive quickfire overview, and I’ll hand over to you now.

Dr Savage: Okay, great. So, in terms of safety, what do you think are the key aspects that we need to be considering with approved and emerging agents?

Dr Mrowietz: Well, from the mode of action and from clinical trials, not only in psoriasis but also in other indications, we've learned that patients with a pre-existing and known inflammatory bowel disease are probably not the ideal candidates for IL-17-based drugs.

We also learned that according to the mechanism of action and the physiological role of IL-17 cytokine family members, Candida infections are more often seen in patients treated with IL-17 inhibitors.

What is quite reassuring is the long-term data that are available right now for the existing IL-17 drugs. These include new data in the large cohort of samples with over 10,000 patients regarding malignancies, and there is no signal indicating increased risk of malignancies in IL-17 treated patients. Also, it is reassuring that in systematic reviews, there were no cases of TB re-activation in patients treated with IL-17 inhibitors in psoriasis. And this suggests that IL-17 inhibitors may be safely used in patients with latent TB who receive an appropriate latent tuberculosis infection (LTBI) treatment.

Dr Savage: Thank you. That's a really comprehensive answer. So, what do you think are the implications of these data on safety, and which patients do you consider as candidates for systemic therapy with IL-17 inhibitors, particularly in light of recent literature, consensus papers, or guidelines?

Dr Mrowietz: Well, I regard patients with moderate to severe plaque psoriasis with known or suspected psoriatic arthritis as candidates for anti-IL-17 inhibitors as well as those with a known cardiovascular co-morbidity.

So, it's an interesting question to discuss what really is moderate to severe psoriasis. And there have been a lot of consensus statements, Delphi's, and guideline recommendations, some saying, for example, diseases involving special areas, failure of topical therapy, such as the consensus of the International Psoriasis Council.

What I regard as particularly important is to keep an eye on what we call impactful disease, and this can be done by using the Upgrade Criteria of the European Consensus. And the Upgrade Criteria defines, for example, involvement of visible areas, involvement of major parts of the scalp that is the itchiest side of the body, involvement of palms and soles, of genitals, and onycholysis or onychodystrophy of at least 2 fingernails, itch leading to scratching, and the presence of treatment-resistant plaques as Upgrade Criteria, although the PASI may be < 10 and the body surface area (BSA) may be < 10. But as this is impactful disease, those patients have moderate to severe disease and need to be treated by effective drugs, such as IL-17 inhibitors.

Dr Savage: Okay, great. And perhaps I could ask you now what are your goals of treatment in psoriasis? And can those goals be achieved using IL-17 inhibitors?

Dr Mrowietz: Yes, I think they can be achieved because what I regard important is a beneficial effect of those inhibitors on all 3 domains of psoriatic inflammation.

In my personal opinion, I think the best treatment goal, in the future at least, would be an absolute PASI. And it's going to be PASI ≤ 2 or ≤ 3. And the second best, in my personal view, is a Physician Global Assessment of 0 or 1. That means clear, almost clear because this is a real, achievable goal.

Then maybe, in addition, that we should use the DLQI, but as you know, it's not really psoriasis-specific, but it's maybe something which is nice to have. And a DLQI of 0 or 1, I think, is another good patient-reported outcome to look at. For me, PASI 100 is an artificial goal, and we have to remember that this came from industry, not from dermatologists.

Well, Laura, next question goes to you. What is the effect of high-impact lesions on quality of life, as we have just alluded to? Are there any data?

Dr Savage: So, psoriasis at visible sites, such as the scalp, the nails, and the palms, or in intimate areas has a profound impact on all aspects of a patient's life, including their self-esteem, interpersonal relationships, and their ability to work.

April Armstrong and colleagues presented some interesting data at the European Academy of Dermatology and Venereology (EADV) meeting last autumn, demonstrating how total DLQI scores varied by body size involvement. And scores were higher for patients with involvement at high-impact areas, such as the nails, the palms, the soles, and the genitals, than the arms and legs when compared with those without psoriasis in that body site.

And this is why most treatment guidelines now advocate that patients should be eligible for biologic therapy if the psoriasis is severe at localized sites and associated with significant functional impairment or high levels of stress.

So, you've already mentioned the Delphi consensus statement from the International Psoriasis Council, whereby the definition of psoriasis severity, basically defined patients with disease involving special areas as candidates for systemic therapy, in addition to those patients that we usually more traditionally think of as candidates for systemic therapy with a body surface area of > 10%.

Dr Mrowietz: Well, that means we need to really have an eye on these impactful areas and impactful disease probably more in the future than we did before. Thanks for this comprehensive overview, Laura.

Dr Savage: No problem. I could ask you now, in clinical practice, in a patient with moderate to severe psoriasis, which key factors steer you to choose an IL-17 inhibitor?

Dr Mrowietz: Well, that's a very important question and I think, for me, it's most important to see, first of all, a benefit in safety, tolerability, plus efficacy of the drug but not in the short-term but in the long-term, because what we want to achieve is a long-term control of our systemic inflammatory scenario.

So, what I regard as very important data are, of course, real-world data, and they are generated from our registries. And for the IL-17 group, of course, there are limited data because they are newer drugs, but the data show a very favorable drug survival of the IL-17s and that's what I need, for example, to choose a drug. In addition, I would like to have, and I mentioned this before, some data about the effect on other domains of the disease.

And you alluded earlier to the fact that IL-17 drugs are efficacious for the skin but also for bones and joints. And there are data, at least for secukinumab, showing in a clinical trial that there is an improvement of perivascular inflammation but also of endothelial cell function when those patients are treated over one year with secukinumab. So, this long-term treatment paradigm is most important for managing these patients.

Dr Savage: Perfect timing. Absolutely succinct. Thank you, Ulrich.

Dr Mrowietz: Thanks, Laura. Next question goes again to you. In clinical practice, in a patient with moderate to severe psoriasis, which factors make you choose a treatment other than an IL-17 inhibitor?

Dr Savage: Okay. So, as you've alluded to, there are several patient- and disease-related factors to consider when selecting a biologic therapy.

So, I usually begin with considering their co-morbidities, and I would choose a treatment other than an IL-17 inhibitor if the patient had a personal or family history of inflammatory bowel disease, or if they had had recurrent fungal infections. I'd also discuss family planning considerations with a female of childbearing age and select an alternative such as certolizumab if she was hoping to conceive in the next 12 months.

And then lifestyle and posology are also important to consider to maximize compliance. And the patient may prefer an IL-23p19 inhibitor dosed every 8 or 12 weeks over a drug dosed every 2 to 4 weeks and as those agents targeting IL-17 are currently. Although that will change with the introduction of bimekizumab, which will be dosed every 8 weeks as no advantage was seen in clinical trials in dosing every 4 weeks.

Dr Mrowietz: Thanks a lot, Laura. This was a very clear guidance, and we are at the end of our expert quickfire. And I would like just to make some concluding remarks.

So, we were discussing the impact of IL-17 inhibitors in the treatment of psoriatic disease. And I think the IL-17 inhibitors are, today, a major part of this biologic drug spectrum we have. They are beneficial for all major domains of psoriatic disease. They are proven to be efficacious in short-, and most importantly, long-term treatment.

They all show a favorable benefit-risk profile. And let’s not forget, they all have a label for first-line treatment.

Laura, thank you very much for this great discussion, and thank you for participating in this activity. And please continue to answer the questions that follow and complete the evaluation.

This transcript has been edited for style and clarity.

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