Focus on Psoriasis

A report from the 2018 Annual Meeting of the American Academy of Dermatology, San Diego, California

By Nicole M. Golbari, MD

Drawing more than 18,000 registrants from 100 countries, the 2018 American Academy of Dermatology’s annual meeting, which took place in February at the San Diego Convention Center, was a vibrant assembly of the novel and compelling innovations in dermatology over the last year. The numerous scientific sessions dedicated to recent advancements in psoriasis gathered large audiences, eager to hear about topics such as the efficacy of emerging biologic treatments, the treatment of psoriasis throughout pregnancy, biologic efficacy on the treatment of cardiovascular inflammation in psoriasis, and more.

Contents and quick links

• Approach to evaluating patients with psoriasis
• Updates in psoriasis
• Psoriasis treatment guidelines
• Emerging treatments
• Late-breaking research
• References

Approach to evaluating patients with psoriasis

Dr. Kristina Callis-Duffin, from the University of Utah and Dr. Joseph Merola from Harvard Medical School presented useful clinical tools for assessing patients with psoriasis. Dr. Callis-Duffin reviewed how to efficiently use body surface area (BSA), physician global assessment (PGA), and the psoriasis area and severity index (PASI) to evaluate disease status in clinic, and introduced the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) phone application as an easy and effective tool for use in the clinical setting. Dr. Merola focused on how dermatologists should assess patients for psoriatic arthritis (PsA), looking for dactylitis, enthesitis, and axial spondyloarthritis,¹ as well as using laboratory monitoring and imaging to help identify an inflammatory arthritic process.

Next, Dr. Bruce Strober from the University of Connecticut discussed psoriasis patient expectations in the context of the rising efficacies of novel therapies. Dr. Strober addressed the dichotomy between the patient and provider approach to treatment decision-making² and affirmed the importance of patient-reported outcomes in the assessment of treatment efficacy. Patients with PASI 100, or completely clear skin, achieve significantly better dermatology life quality index (DLQI) scores than those who achieve almost clear skin.^3,4 Additionally, once patients’ skin is clear, regression of disease can lead to profound and disproportionate quality of life (QoL) impact. Dr. Strober presented data showing that the same PASI score predicts worse DLQI score if the patient has previously experienced clearance of psoriasis than if they had never been clear.⁵ This data suggests that practitioners should be mindful of QoL impact when considering dose reduction or discontinuation of treatment.

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Updates in psoriasis

Dr. Mark Lebwohl, chairman of the department of dermatology at Icahn School of Medicine at Mount Sinai, New York City, began the session with a presentation addressing how to decide which systemic psoriasis treatments are most appropriate for a given patient, focusing on treatment in patients with systemic lupus erythematosus, multiple sclerosis, Crohn’s disease, hepatitis infection and HIV.

Meanwhile, Dr. Joel Gelfand from the University of Pennsylvania Perelman School of Medicine, Philadelphia, addressed the increased cardiovascular risk in psoriasis patients. While observational studies have suggested that methotrexate and TNF-alpha inhibitors have a protective effect on the risk of cardiovascular events, the data currently available for other biologic agents are less suggestive.⁶ Dr. Gelfand presented results from a recent randomized control trial that failed to demonstrate any difference in the vascular inflammation of the aorta and carotid arteries secondary to TNF-alpha treatment.⁷ However, newer studies, including the Vascular Inflammation in Psoriasis (VIP) Trials, are currently underway and may elucidate the effects of adalimumab (NCT01553058), ustekinumab (NCT02187172), and secukinumab (NCT02690701) on systemic inflammation and cardiovascular risk factors patients with moderate to severe psoriasis. (See section on “Late breaking research”)

Dr. Kenneth Gordon, chair of dermatology and the Medical College of Wisconsin, Milwaukee, and Dr. Richard Langley, from Dalhousie University, Nova Scotia, Canada, engaged in a lively debate over which agents should be used first in psoriasis treatment: traditional systemic agents or biologics. Dr. Gordon argued that not only are traditional systemic agents cheaper than biologics, but some agents, such as methotrexate, are also able to achieve PASI 75 efficacy in up to 40% of patients.⁸ Dr. Langley contended that systemic agents should be bypassed for biologic treatment that is “immediate, durable and convenient.” He presented data from the ERASURE and VOYAGE1 trials, which demonstrated that Interleukin (IL)-17 and IL-23 inhibition is able to achieve PASI 75 in up to 90% and PASI 100 in almost 50% of patients.^9,10 Ultimately, while the majority of attendees agreed that biologics are the preferred first agent for treatment, Dr. Gordon was able to convince a portion of their audience to change their votes to support a trial of traditional systemic agents before escalating to biologics.

Following the debate, Dr. Alan Menter, chair of dermatology at Baylor University, Dallas, Texas, and founding president of the IPC, and Dr. Boni Elewski, chair of dermatology at University of Alabama at Birmingham, presented an updated overview of genital and nail psoriasis, respectively. While both genital and nail psoriasis demonstrate a unique impact on quality of life, few studies focus on these areas as the primary endpoint. To date, ixekizumab is the only biologic agent studied for genital psoriasis and Dr. Menter presented new data showing that ixekizumab was able to achieve significant improvement in QoL scores and a static PGA score of clear or almost clear in 73% of subjects.

Dr. Alexa Kimball, professor of dermatology at Harvard Medical School and current president of the IPC, closed the session with a lecture on psoriasis treatment in pregnant and lactating patients, focusing on emerging data regarding biologic therapy during pregnancy. While risk of congenital anomaly is typically highest in first trimester of pregnancy, data available on the use of ustekinumab, certolizumab pegol, ixekizumab, tofacitinib, and etanercept in pregnant patients is reassuring as risks of major congenital malformations is not higher than in the U.S. General Population. Similarly, case reports for infliximab and etancercept, and studies on certolizumab pegol demonstrate minimal transfer from plasma to breast milk. However, active transfer of IgG across the placenta is highly efficient in the third trimester of pregnancy and live vaccines such as the rotavirus inoculation should perhaps be avoided, as there is the potential for neonatal immunosuppression in biologic-treated mothers. Dr. Kimball presented data suggesting that etanercept and certolizumab have the least placental transfer of the TNF-alpha agents and might be considered for mothers seeking treatment throughout their pregnancies. ^11,12

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Psoriasis treatment guidelines

Dr. Craig Elmets, from the University of Alabama at Birmingham and chair of a session on psoriasis treatment guidelines, began the discussion by presenting an overview of the current understanding of psoriasis pathogenesis, elucidating why the TNF-alpha, IL-17, IL-12, IL-23, PDE-4 and JAKSTAT pathways are appropriate targets for psoriasis drug development.

Continuing the session, Dr. Lebwohl presented the current guidelines for monitoring patients on systemic therapy. For patients on methotrexate, bone marrow, renal, and liver function must be monitored. Dr. Lebwohl specifically addressed how guidelines for liver biopsy have eased over time, emphasizing that risks involved with biopsy are not nominal. Biopsy should be considered strongly for high-risk patients such as those with alcoholism, preexisting liver disease, diabetes, or obesity. Dr. Lebwohl also reviewed the guidelines for cyclosporine monitoring. He discussed the risk of nephrotoxicity and hypertension, citing an article that demonstrated minimal hypertension and reduced creatinine levels in transplant patients on cyclosporine who were concurrently treated with amlodipine. ¹³ Nevertheless, blood pressure, creatinine, lipids, and blood counts should be monitored in psoriasis patients treated with cyclosporine.

Dr. Henry Lim of the Henry Ford Health System in Detroit and outgoing president of the AAD, reviewed the guidelines for phototherapy treatment, specifically protocol for narrow band-UVB (ultraviolet light B), PUVA (psoralen and ultraviolet light A), and targeted phototherapy with 308-nm excimer laser. Dr. Lim underscored the advantages of phototherapy, in particular how targeted phototherapy is ideal for patients with <10% BSA who are resistant to other treatments.

Lastly, Dr. Craig Leonardi, from Saint Louis University, Missouri, summarized the recommendations from the 2011 American Academy of Dermatology Work Group guidelines updates,¹⁴ focusing on cases of recalcitrant psoriasis and difficult-to-manage comorbidities.

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Emerging treatments

In the same Sunday morning session, Dr. Alice Gottlieb of New York Medical College, Valhalla, New York, presented data on emerging biologic therapies for psoriatic arthritis. She highlighted the importance of effectively treating both joint and skin disease to achieve optimal health-related QoL, ultimately concluding that while tofacitibib (Janus kinase inhibitor), abatacept (which targets T-cell activiation), and TNF-alpha, IL-17, and IL-23 inhibitors have all shown efficacy in the treatment of symptoms of peripheral arthritis, tofacitibib and abatacept show less efficacy in the treatment of skin disease.

Dr. Menter, who chaired the session with Dr. Elmets, presented an enlightening overview of the emerging psoriasis therapies currently in the pipeline, including promising biologics such as risankizumab, tildrakizumab (IL-23 inhibitors) and certolizumab (TNF-alpha inhibitor), which are currently in phase 3 trials. Dr. Menter concluded his talk with a practical discussion about biosimilars in psoriasis. Given the difficulty in generating biologic agents, the integrity and consistency of biologic biosimilars must be considered, as there is the potential for variation in pharmacokinetic and pharmacodynamic performance.¹⁵

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Late-breaking research

During the session on late-breaking research in clinical trials, Dr. Kristian Reich from Georg-August-University Göttingen and the Dermatologikum in Hamburg, Germany, presented data from the VOYAGE 2 trial on the long-term efficacy of guselkumab treatment. Approximately 86% of patients who received continuous guselkumab therapy for the 76-week study were able to maintain PASI 90. Of the patients who were randomly withdrawn from the treatment group after 28 weeks, 88% were able to regain a PASI 90 response after reinitiating treatment. Dr. Reich noted that these results are reassuring for patients who need to interrupt treatment, as these data demonstrate that they can regain excellent disease response rates. Dr. Reich also addressed the potential for disease modification, as patients who maintained disease response after withdrawal of treatment demonstrated suppressed serum levels of IL-17A, IL-17F and IL-22.

Dr. Gordon presented exciting efficacy and safety data from phase 3 trials on risankizumab, an IL-23 inhibitor. Risankizumab has shown excellent efficacy with 75% of patients achieving PASI 90 at week 16 compared to 5% who were on placebo and 42% on ustekinumab. Additionally, more than 50% of patients on risankizumab achieved PASI 100 at week 52, the highest PASI 100 response reported yet.

Finally, Dr. Gelfand presented preliminary results from a VIP phase 4 trial examining the effect of ustekinumab on cardiovascular inflammation in psoriasis. The information presented demonstrated that, in addition to efficacy in skin, ustekinumab showed a 6.6% reduction in aortic vascular inflammation, a statistically significant reduction compared with those who received placebo. While it was previously thought the TNF-alpha inhibitors were the most effective agents for reducing cardiovascular risks, recent studies with positron emission tomography-computed tomography have demonstrated no improvement in vascular inflammation for patients treated with adalimumab.⁷ This VIP study, still ongoing, suggests that ustekinumab, an IL-12 and IL-23 inhibitor, may be effective in reducing vascular risk in patients with psoriasis.

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References

1. Cohen JM, Husni ME, Qureshi AA, Merola JF. Psoriatic arthritis: it’s as easy as “PSA”. J Am Acad Dermatol 2015; 72: 905-6.
2. Tan J, Stacey D, Barankin B, et al. Support needed to involve psoriasis patients in treatment decisions: survey of dermatologists. J Cutan Med Surg 2011; 15(4):192-200.
3. Edson-Heredia E, Banerjee S, Zhu B et al. A high level of clinical response is associated with improved patient-reported outcomes in psoriasis: analyses from a phase 2 study in patients treated with ixekizumab. J Eur Acad Dermatol Venereol 2016; 30:864–5.
4. Revicki DA, Willian MK, Menter A, Saurat JH, Harnam N, Kaul M. Relationship between clinical response to therapy and health-related quality of life outcomes in patients with moderate to severe plaque psoriasis. Dermatology 2008;216:260-270.
5. Poulin Y, Sheth P, Gu Y, Teixeira HD. Health-related quality of life worsens eisproportionately to objective signs of psoriasis after withdrawal of adalimumab therapy. Dermatol Ther (Heidelb) 2014; 4: 33–42.
6.  Rungapiromnan W, Yiu ZZN, Warren RB, Griffiths CEM, Ashcroft DM. Impact of biologic therapies on risk of major adverse cardiovascular events in patients with psoriasis: systematic review and meta-analysis of randomised controlled trials. Br J Dermatol 2017;176(4):890–901.
7. Bissonnette R, Harel F, Krueger JG, et al. TNF-α antagonist and vascular inflammation in patients with psoriasis vulgaris: a randomized placebo-controlled study. J Invest Dermatol, 2017;137:1638-1645.
8. Warren RB, Mrowietz U, von Kiedrowski R, et al. An intensified dosing schedule of subcutaneous methotrexate in patients with moderate to severe plaque-type psoriasis (METOP): a 52 week, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2016; 389(10068):528-537.
9.  Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis: results of two phase three trials. N Engl J Med 2014 371:326-338.
10. Blauvelt, A., Papp, K., Griffiths, CE, et al. Efficacy and safety of guselkumab, an anti-IL-23 monoclonal antibody, compared with adalimumab for the continuous treatment of moderate-to-severe psoriasis: results from the phase III VOYAGE 1 trial. J Am Acad Dermatol. 2017;76:405–417.
11. Berthelsen BG, Fjeldsøe-Nielsen H, Nielsen CT, Hellmuth E. Etanercept concentrations in maternal serum, umbilical cord serum, breast milk and child serum during breastfeeding. Rheumatology (Oxford) 2010;49:2225–2227.
12.  Mariette X, Förger F, Abraham B, Flynn AD, Moltó A, et al. Lack of placental transfer of certolizumab pegol during pregnancy: results from CRIB, a prospective, postmarketing, pharmacokinetic study. Ann Rheum Dis 2018;77(2):228-233.
13. Venkat Raman G, Feehally J, Coates RA, Elliott HL, Griffin PJ, et al. Renal effects of amlodipine in normotensive renal transplant recipients. Nephrol Dial Transplant. 1999;14(2):384-8.
14. American Academy of Dermatology Work Group, Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 6. Guidelines of care for the treatment of psoriasis and psoriatic arthritis: case-based presentations and evidence-based conclusions. J Am Acad Dermatol 2011;65(1):137-74.
15. Strober BE, Armour K, Romiti R, et al. Biopharmaceuticals and biosimilars in psoriasis: what the dermatologist needs to know. J Am Acad Dermatol 2012;66(2):317-322.

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