Focus on Psoriasis

A report from the 2019 Annual Meeting of the American Academy of Dermatology, Washington, DC

By Kelsey Flood, MD & Kevin T. Savage, BA

More than 18,000 dermatologists from across the globe descended on Washington, DC, earlier this year for the 2019 American Academy of Dermatology Annual Meeting. Sessions showcased advances in medical and surgical treatment of dermatologic disease and offered fascinating insights into dermatology’s future. As in past meetings, psoriasis took center stage, with several presentations covering exciting preliminary results from groundbreaking studies that promise to revolutionize our understanding and treatment of this burdensome disease.

Contents and quick links

• Emerging therapies
• JAK inhibitors
  
• Inflammatory skin diseases & the translational revolution
  
• Biologic overload
  
• Controversies, difficult questions concerning biologics
  
• Psoriasis treatment updates
  
• Late-breaking sessions
  
• Comorbidities in psoriasis
  
• Systemic therapies: A comprehensive review
  
• Hand and foot psoriasis
  
• The pregnant pause
  
• References

emerging therapies

In this session, Dr. Leon Kircik of the Icahn School of Medicine at Mount Sinai, New York, discussed new treatments for psoriasis, including the tyrosine kinase 2 (TYK2) inhibitor BMS-986165. TYK2 is a member of the Janus kinase (JAK) family of enzymes. In a phase 2 study of BMS-986165, 75% of patients (33 of 44 patients) obtained a 75% or greater reduction in the Psoriasis Area and Severity Index (PASI) score, treated with 12 mg daily (P<0.001 vs. placebo). One case of melanoma was reported 96 days after the start of treatment. Interestingly, acne was also noted as an adverse event in the phase 2 trial, and 4 reports of acne were made in the 12-mg daily BMS-986165 treatment group.¹

The safety profile of JAK inhibitors is still being studied. Safety concerns with JAK inhibitors include increased risk of infection and potential malignancy risk. Additional longitudinal data are necessary to understand if there is an increased risk of malignancy associated with JAK inhibitors.² There may be a signal for increased risk of thromboembolism, although this also needs further study.³

Regarding biologics, Dr. Kircik reviewed ixekizumab use for genital psoriasis. In the IXORA-Q study, treatment with ixekizumab led to improvement in both genital psoriasis symptoms and the impact of genital psoriasis on sexual activity.⁴ He also discussed the IL-17 inhibitors brodalumab and bimekizumab. In the AMAGINE-2 and AMAGINE-3 phase 3 clinical trials, the cohort treated with 210 mg of brodalumab had significantly higher PASI 100 rates at week 12 compared to those treated with ustekinumab. With a lower dose of brodalumab (140 mg), the PASI 100 rates were significantly higher compared to ustekinumab in AMAGINE-3 but not AMAGINE-2.⁵

Bimekizumab, with a unique mechanism of action, targets 3 cytokines - IL-17A, IL-17F - and the IL-17A/F heterodimer. In a late-breaking session, Dr. Andrew Blauvelt of the Oregon Medical Research Center discussed 60-week extension results for bimekizumab treatment in psoriasis. In the BE ABLE1 study, 69-83% of patients achieved PASI 90 by week 60, including 90% of placebo patients who crossed over to bimekizumab.

Dr. Kircik also discussed tildrakizumab and risankizumab, biologics that target IL-23. In a study comparing risankizumab to secukinumab, 77% of patients achieved a PASI 90 score and 45% achieved PASI 100 in the pooled 90-mg and 180-mg risankizumab cohorts.⁶

Finally, Dr. Kircik discussed the application of agents that historically are used for other indications and have more recently been applied to psoriasis. Fumarates, such as dimethyl fumarate, which is FDA-approved for multiple sclerosis⁷ and has been used by some countries such as Germany for psoriasis in the past, was approved by the European Medicines Agency for psoriasis in 2017.8

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jak inhibitors

A presentation by Dr. April Armstrong of the Keck School of Medicine of the University of Southern California focused on JAK inhibitors. The JAK-STAT pathway, via IL-12 and IL-23 signaling, is significant in psoriasis pathogenesis. Two phase 3 clinical trials of BMS-986165, a TYK-2 inhibitor, are currently underway.

Dr. Armstrong also discussed tofacitinib, a JAK inhibitor, approved by the US Food and Drug Admimnistration for treating psoriatic arthritis. In the OPAL Broaden phase 3 clinical trial, the American College of Rheumatology (ACR) 20 (>20% improvement) response rates were 50% and 61% in the tofacitinib 5-mg, twice-daily (BID) and 10-mg BID cohorts, respectively.⁹ For psoriasis, phase 3 clinical trials demonstrated noninferiority of 10 mg BID tofacitinib to 50 mg of etanercept twice weekly, although this was not replicated for the 5-mg BID cohort. In a phase 2b clinical trial of the JAK inhibitor baricitinib, 43% (8 mg daily) and 54% of patients (10 mg daily) achieved PASI 75 rates.¹⁰

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inflammatory skin diseases & the translational revolution

Dr. Mark Lebwohl of the Icahn School of Medicine at Mount Sinai discussed the history of psoriasis treatment, highlighting recent achievements in pathogenic understanding and their impact on therapeutic development. Dr. James Krueger, of The Rockefeller University, New York, provided an update on psoriasis pathogenesis and therapies, including a discussion of the aberrant IL-23/T-helper (Th)-17 signaling axis responsible for disease development and maintenance.¹¹ He posited that psoriasis represents the most successful case of molecular therapeutic targeting altering a human disease, and noted the “molecular scar” of abnormal gene expression following treatment appears to be shrinking with each new treatment.

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biologic overload

Dr. George Han of the Icahn School of Medicine noted that IL-12/23 and IL-17 inhibitors’ success has minimized disparities in biologic regimen choice. He discussed infections in biologic-treated patients, noting similar infection rates with both biologics and placebo, suggesting rates of serious infection with biologics are lower than previously thought.

Dr. Jeffrey Weinberg, also of the Icahn School of Medicine, provided an update on the biologic development pipeline. He expressed encouragement regarding results for risankizumab, an anti-IL-23 antibody, and bimekizumab, a dual anti-IL-17A and IL-17F antibody. Specifically, he mentioned phase 2b trial data for bimekizumab, in which 50-60% of the highest-dosing groups achieved PASI 100 by week 12, a level never seen before.¹² He also discussed nonbiologic options, including the TYK2 inhibitor BMS-986165, which offers significant clearance and fewer side effects compared to JAK inhibitors such as tofacitinib.

Dr. Russell Cohen of South Nassau Dermatology, New York, discussed alternative treatments to biologics including phototherapy, methotrexate, and cyclosporine. He reviewed sometimes overlooked options such as phototherapy (PASI 75 rates between 63-80%) and methotrexate (PASI 75 rates of 36% after 4 months¬). He also discussed cyclosporine, which is a useful tool as a bridge to other treatment options. Additionally, acitretin is efficacious for palm and sole involvement, whereas apremilast is effective for scalp and nail disease.

Dr. Kristina Callis Duffin of the University of Utah presented on the 2018 American College of Rheumatology/National Psoriasis Foundation guidelines for treating psoriatic arthritis. In treatment-naïve patients, first-line therapy is a tumor necrosis factor (TNF) inhibitor. If symptoms persist, the guidelines recommend trying a different TNF inhibitor. Interestingly, in the SPIRIT-H2H trial, patients treated with ixekizumab, compared to adalimumab, were more likely to achieve ACR 50 and PASI 100.¹³

Dr. Kenneth Gordon of the Medical College of Wisconsin reviewed challenging psoriasis cases. In pregnancy, concern exists that biologics may impact a newborn’s immune system and response to vaccination. Despite exposure to anti-TNF therapy in utero, however, data suggest maternal biologic use does not seem to affect the infant. Therefore, Dr. Gordon suggested, it is likely safe to continue treatment with TNF inhibitors during pregnancy.

For patients with psoriasis and psoriatic arthritis, he recommended tailoring treatment to tackle both conditions. For patients with psoriasis, psoriatic arthritis, and inflammatory bowel disease, he recommended anti-TNF therapy or tofacitinib and ustekinumab as nontraditional options.

Dr. Abby Van Voorhees of Eastern Virginia Medical School summarized considerations when starting patients on biologic therapies. She cautioned against anti-IL-17 use in patients with inflammatory bowel disease and highlighted living situation as a key determinant when deciding between oral or biologic therapy.

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controversies, difficult questions concerning biologics

In this presentation, Dr. Kenneth Gordon challenged the applicability of a new, stringent psoriasis treatment recommendation made by National Psoriasis Foundation, setting a target of <1% body surface area (BSA) at 6 months of treatment during the maintenance period.14 He posited that this recommendation is acceptable on a population scale, but falters on an individual basis, citing the neutral cardiovascular risk in patients under 10% BSA. Instead, Dr. Gordon argued that below 10% BSA, psoriasis should be viewed and treated as a Quality of Life (QoL) issue to avoid unnecessary patient cost and risk.

Dr. Jashin Wu, Dermatology Research and Education Foundation, California, discussed active comparator trials for BMS-986165, touting its narrow range of inhibition as an advantage over other JAK inhibitors. He presented data showing that 69% of patients treated with BMS-986165 ≥ 3 mg twice daily achieved PASI 75 at 12 weeks, which is superior to methotrexate, acitretin, and apremilast, and on par with several biologics.¹

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psoriasis treatment updates

Dr. Mark Lebwohl discussed biologics in patients with complex comorbidities. For patients with hepatitis C, he suggested etanercept, which when used in conjunction with antivirals results in less liver scarring and better viral control.¹⁵ He also discussed TB reactivation. As TNF is involved in clearing mycobacterial infections, reactivation is observed with TNF inhibitors.¹⁵ TB reactivation has not been reported with IL-23 and IL-17 blockers,¹⁵ although screening is still encouraged. Methotrexate and high-dose cyclosporine have been associated with TB reactivation.¹⁵ Dr. Lebwohl also reviewed the ATTACH trial, in which high-dose infliximab was associated with more frequent hospitalizations and deaths in patients with class III or IV heart failure.¹⁶

Dr. Andrew Blauvelt discussed novel therapeutic agents. He described the UltIMMa-1 and UltIMMa-2 trials investigating risankizumab, in which 80% of patients achieve PASI 90 rates at 1 year.¹⁷ He also discussed data for other emerging biologics including bimekizumab, mirikizumab, and BMS-986165.

In her presentation, Dr. Alexa Boer Kimball of Beth Israel Deaconess Medical Center in Massachusetts discussed psoriasis treatment in pregnancy. Pregnancy outcomes are worse in patients with psoriasis, and this risk is higher in patients with greater disease severity.¹⁸ Although disease control may hypothetically abate negative pregnancy outcomes, treating pregnant patients is difficult. Because pregnant women are excluded from clinical trials, prohibiting data-gathering on safety in pregnancy, pregnancy risk is poorly established for many agents.¹⁹

Dr. Kimball noted that ultraviolet B (UVB) radiation therapy has no FDA pregnancy risk category, whereas topical steroids and calcipotriol are pregnancy category C (drugs should be given only if the potential benefit justifies the potential risk to the fetus). Many biologics are transferred from the mother to the infant via the placenta, and IgG levels in the fetal circulation correspond with gestational age.²⁰ Concern exists that maternal biologic use will promote newborn immunosuppression, although this potential risk needs to be further investigated. Nonetheless, live vaccines should be avoided in infants exposed to biologics in utero. Certolizumab is thought to be safer in pregnancy as it is pegylated, which results in less maternal-fetal transfer across the placenta.²¹ Finally, Dr. Kimball discussed use of biologics during breastfeeding. TNF inhibitors, for example, are likely safe for use in breastfeeding patients as miniscule amounts are secreted into human breast milk and are also likely minimally absorbed by the infant.

Dr. Kelly Cordoro of the University of California San Francisco discussed pediatric psoriasis and stressed the importance of identifying triggers, especially strep infections. For limited disease, steroids and vitamin D analogues are first-line therapy. Data supporting use of topical calcineurin inhibitors are sparse. Phototherapy is another first-line choice. Systemic therapies administered to children are similar to those given to adults: methotrexate, cyclosporine, acitretin and biologics. FDA-approved biologics for children include etanercept and ustekinumab. However, Dr. Cordoro explained that all biologics can be considered and used to individualize treatment.

Dr. Wu reviewed studies demonstrating that treatment of psoriasis can impact cardiovascular comorbidities. Ustekinumab, for example, led to improvement in vascular inflammation.²² He also discussed evidence that improvement in psoriasis was associated with a concurrent decrease in non-calcified coronary plaque burden.²³ Additionally, anti-TNF biologic treatment has been associated with decreased major adverse cardiovascular events.²⁴

Dr. Kenneth Gordon and Dr. Richard Langley of Dalhousie University, Canada, followed with a debate on treating to a standardized target. Dr. Gordon argued that this method is ineffective as it is not individualized to the patient. Further, he argued that treating to a standard target is costly and may require unnecessary exposure to multiple drugs before finding an effective agent. Dr. Langley countered that treating to a clinically relevant endpoint provides focus, allows for progress to be measured, and improves patient outcomes. For example, greater improvement in PASI scores correlates with a greater improvement in quality of life.

Dr. Lebwohl concluded the session by discussing malignancy risk with biologics. Adalimumab treatment is associated with an increased signal for lymphoma and nonmelanoma skin cancer. However, cumulative risk for all malignancies appears not to increase. He reported that IL-23 and IL-17 biologics appear to be safer to use in cancer patients. Methotrexate and cyclosporine are associated with increased risk of cancer, whereas acitretin is safe in patients with malignancy.

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late-breaking sessions

Dr. Sascha Gerdes of the University Medical Center Schleswig-Holstein in Germany discussed the IL-17 inhibitor secukinumab’s impact on quality of life (QoL) in patients with psoriasis as demonstrated in the PROSE study. All study groups – treatment naïve, prior systemic therapy, and prior biologic therapy – showed marked QoL improvement at week 16, with 70.8% of patients achieving a Dermatology Life Quality Index score of 0-1.

Dr. Joel Gelfand of the University of Pennsylvania presented preliminary results of the Vascular Inflammation in Psoriasis (VIP) secukinumab trial using 18FDG-PET-CT to quantify secukinumab’s effect on aortic wall inflammation. Secukinumab offered significant skin clearance at week 12 (74% scored PASI 75). However, no difference in vascular inflammation was found compared to placebo.

Dr. Mary Spellman from the biopharmaceutical company Menlo Therapeutics Inc. presented results from the PSORIXA phase 2 trial of the agent serlopitant, a small-molecule neurokinin 1 (NK1) receptor antagonist, which the company developed to control psoriasis-associated pruritus. Serlopitant offered a significantly greater reduction in itch numeric rating scale compared to placebo (33.3% vs. 21.1%) with no major side effects.

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comorbidities in psoriasis

Dr. Ronald Prussick of George Washington University, Washington, DC, reviewed comorbidities in psoriasis, discussing increased all-cause mortality in patients with >10% BSA.²⁵ He urged clinicians to proactively counsel patients on weight loss and exercise, stressing the high rate of nonalcoholic fatty liver disease and metabolic syndrome in patients with psoriasis.^26,27 Given TNF inhibitors’ ability to reduce depression risk, he recommended screening all patients for depression.²⁸

Dr. Nehal Mehta, a cardiologist from the National Institutes of Health, Bethesda, Maryland, characterized cardiovascular risk in psoriasis patients, citing a 2-fold risk of myocardial infarction between the ages of 40-50 years. While observational studies support an increased risk of cardiovascular disease in patients with psoriasis, Dr. Mehta cautioned that randomized clinical trial data are unclear, as the Vascular Inflammation in Psoriasis (VIP) Extension (using adalimumab) and VIP-secukinumab studies failed to find decreased aortic vascular inflammation compared to placebo. Encouragingly, he presented findings of an 8-12% reduction in coronary artery plaque volume in biologic-treated patients compared to a net increase in non-biologic treated patients.

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systemic therapies: a comprehensive review

Dr. Martina Porter of Beth Israel Deaconess Medical Center, Massachusetts, presented useful pearls for managing biologic-treated patients with psoriasis. She discussed important laboratory monitoring, including baseline tuberculosis (TB) and hepatitis screening, followed by annual TB testing. Due to increased risk of nonmelanoma skin cancer, patients treated with TNF inhibitors should also receive yearly total body skin examinations.

Dr. Sonal Shah of the University of California San Francisco discussed her vaccination approach in patients receiving systemic immunosuppression to treat psoriasis. She underscored the absolute contraindication for live vaccines, but noted that killed or subunit vaccines may be given if necessary. Varicella status should be ascertained either by history or serologic immunity and varicella zoster vaccination should be provided prior to immunosuppression. Pneumococcal vaccination is recommended with either the 23-valent polysaccharide vaccine prior to initiation or the 13-valent conjugated vaccine followed by the 23-valent polysaccharide vaccine 8 weeks later in those whose immune system is already suppressed.

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hand and foot psoriasis

Dr. Robert Bissonnette of Innovaderm Research Inc, a Canadian clinical research firm specializing in dermatology, explained the controversy surrounding palmoplantar pustulosis and palmoplantar pustular psoriasis as separate disease entities and highlighted recent data suggesting a potential bacterial role in pustule formation.^29,30 He recommended that physicians evaluating patients with palmoplantar pustulosis test for thyroid disease yearly, encourage smoking cessation, test for anti-gliadin antibody titers, and suggest a gluten-free diet in recalcitrant patients.³¹

Dr. Bruce Strober of the University of Connecticut expounded on the therapeutic challenge of pustular psoriasis. He proposed that all patients with palmoplantar pustular disease be considered moderate to severe, given the condition’s dramatic impact on quality of life. Dr. Strober advocated for a combination approach to treatment and noted that secukinumab’s failure in the 2PRECISE study to adequately treat palmoplantar disease should preclude its use.³²

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the pregnant pause

In discussing psoriasis and pregnancy, Dr. Strober dispelled misconceptions about treatment during pregnancy, asserting that many classic adverse effects are more aptly explained by severe underlying systemic disease rather than the medications themselves. He noted that TNF inhibitors have the most pregnancy data – specifically etanercept and infliximab – and are all likely safe, especially certolizumab-pegol which does not cross the placenta.³³ Although data are limited for the IL-12/23 and IL-17 classes, they appear safe thus far as well. Overall, Dr. Strober was comfortable with most psoriasis treatments in pregnancy, excluding methotrexate.

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References

1. Papp K, Gordon K, Thaçi D, et al. Phase 2 Trial of Selective Tyrosine Kinase 2 Inhibition in Psoriasis. N Engl J Med. 2018; 379:1313-21.
2. Winthrop KL. The emerging safety profile of JAK inhibitors in rheumatic disease. Nat Rev Rheumatol. 2017 Apr;13(4):234-43.
3. Verden A, Dimbil M, Kyle R, Overstreet B, Hoffman KB. Analysis of Spontaneous Postmarket Case Reports Submitted to the FDA Regarding Thromboembolic Adverse Events and JAK Inhibitors. Drug Saf. 41, 357–61 (2018). 2018 Apr;41(4):357-61.
4. Yosipovitch G, Foley P, Ryan C, et al. Ixekizumab Improved Patient-Reported Genital Psoriasis Symptoms and Impact of Symptoms on Sexual Activity vs Placebo in a Randomized, Double-Blind Study. J Sex Med. 2018 Nov;15(11):1645-52.
5. Lebwohl M, Strober B, Menter MA, et al. Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis. N Engl J Med. 2015;373:1318-28.
6. Papp KA, Blauvelt A, Bukhalo, et al. Risankizumab versus Ustekinumab for Moderate-to-Severe Plaque Psoriasis. N Engl J Med. 2017; 376:1551-60.
7. Biogen. TECFIDERA(dimethyl fumarate) delayed-release capsules. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204063lbl.pdf.
8. Dimethyl fumarate for psoriasis. Drug Ther Bull. 2017 Dec;55(12):141–144.
9. Mease P, Hall S , FitzGerald O, et al. Tofacitinib or Adalimumab versus Placebo for Psoriatic Arthritis. N Engl J Med. 2017;377:1537-50
10. Papp KA, Menter MA, Raman M, et al. A randomized phase 2b trial of baricitinib, an oral Janus kinase (JAK) 1/JAK2 inhibitor, in patients with moderate-to-severe psoriasis. Br J Dermatol. 2016 Jun;174(6):1266-76.
11. Hawkes JE, Chan TC, Krueger JG. Psoriasis pathogenesis and the development of novel targeted immune therapies. J Allergy Clin Immunol. 2017 Sep;140(3):645-53.
12. Papp KA, Merola JF, Gottlieb A, et al. Dual neutralization of both interleukin 17A and interleukin 17F with bimekizumab in patients with psoriasis: Results from BE ABLE 1, a 12-week randomized, double-blinded, placebo-controlled phase 2b trial. J Am Acad Dermatol. 2018 Aug;79(2):277-86.e10.
13. Franki L. Positive results reported for ixekizumab versus adalimumab in PsA. MDedge Rheumatology. 2018 December.
14. Armstrong AW, Siegel MP, Bagel J, et al. From the Medical Board of the National Psoriasis Foundation: Treatment targets for plaque psoriasis. J Am Acad Dermatol. 2017 Feb;76(2):290-98.
15. Kaushik SB, Lebwohl MG. Psoriasis: Which therapy for which patient: Psoriasis comorbidities and preferred systemic agents. J Am Acad Dermatol. 2019 Jan;80(1):27-40.
16. Chung ES, Packer M, Lo KH, et al. Randomized, Double-Blind, Placebo-Controlled, Pilot Trial of Infliximab, a Chimeric Monoclonal Antibody to Tumor Necrosis Factor-α, in Patients With Moderate-to-Severe Heart Failure. Circulation. 2003 Jul 1;107(25):3133-40.
17. 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 Aug 25;392(10148):650-61.
18. Bröms G, Haerskjold A, Granath F, Kieler H, Pedersen L, Berglind IA. Effect of Maternal Psoriasis on Pregnancy and Birth Outcomes: A Population-based Cohort Study from Denmark and Sweden. Acta Derm. Venereol. 98, 728–734 (2018).
19. Flood, KS, Porter ML, Kimball AB. Use of biologics in pregnancy: limitations stemming from clinical trials and registry experience. J Eur Aca. Dermatol Venereol. jdv.15552 (2019). doi:10.1111/jdv.15552
20. Malek A, Sager R, Kuhn P, Nicolaides K H, Schneider H. Evolution of maternofetal transport of immunoglobulins during human pregnancy. Am J Reprod Immunol. 1996 Nov;36(5):248-55.
21. Porter ML, Lockwood SJ, Kimball AB. Update on biologic safety for patients with psoriasis during pregnancy. Int J Womens Dermatol. 2017 Mar; 3(1): 21–25.
22. Kim BS, Lee WK, Pak K, et al. Ustekinumab treatment is associated with decreased systemic and vascular inflammation in patients with moderate-to-severe psoriasis: Feasibility study using 18F-fluorodeoxyglucose PET/CT. J Am Acad Dermatol. 2018 Mar 17. pii: S0190-9622(18)30461-4.
23. Lerman JB, Joshi AA, Chaturvedi A, et al. Coronary Plaque Characterization in Psoriasis Reveals High-Risk Features That Improve After Treatment in a Prospective Observational Study. Circulation. 2017 Jul 18;136(3):263-76.
24. Wu JJ, Joshi AA, Reddy SP, et al. Anti-inflammatory therapy with tumour necrosis factor inhibitors is associated with reduced risk of major adverse cardiovascular events in psoriasis. J Eur Acad Dermatol Venereol. 2018 Mar 24.
25. Noe MH, Shin DB, Wan MT, Gelfand JM. Objective Measures of Psoriasis Severity Predict Mortality: A Prospective Population-Based Cohort Study. J Invest Dermatol. 2018 Jan;138(1):228-30.
26. Miele L, Vallone S, Cefalo C, et al. Prevalence, characteristics and severity of non-alcoholic fatty liver disease in patients with chronic plaque psoriasis. J Hepatol. 2009 Oct;51(4):778-86.
27. Danielsen K, Wilsgaard T, Olsen AO, et al. Elevated odds of metabolic syndrome in psoriasis: a population-based study of age and sex differences. Br J Dermatol. 2015 Feb;172(2):419-27.
28. Strober B, Gooderham M, de Jong EMGJ, et al. Depressive symptoms, depression, and the effect of biologic therapy among patients in Psoriasis Longitudinal Assessment and Registry (PSOLAR). J Am Acad Dermatol. 2018 Jan;78(1):70-80.
29. Masuda-Kuroki K, Murakami M, Tokunaga N, et al. The microbiome of the "sterile" pustules in palmoplantar pustulosis. Exp Dermatol. 2018 Dec;27(12):1372-1377.
30. Bissonnette R, Suárez-Fariñas M, Li X, et al. Based on Molecular Profiling of Gene Expression, Palmoplantar Pustulosis and Palmoplantar Pustular Psoriasis Are Highly Related Diseases that Appear to Be Distinct from Psoriasis Vulgaris. PLoS One. 2016 May 6;11(5):e0155215.
31. Michaëlsson G, Kristjánsson G, Pihl Lundin I, Hagforsen E. Palmoplantar pustulosis and gluten sensitivity: a study of serum antibodies against gliadin and tissue transglutaminase, the duodenal mucosa and effects of gluten-free diet. Br J Dermatol. 2007 Apr;156(4):659-66.
32. Mrowietz U, Bachelez H, Burden AD, et al. Secukinumab for moderate-to-severe palmoplantar pustular psoriasis: Results of the 2PRECISE study. J Am Acad Dermatol.2019 Feb 1. pii: S0190-9622(19)30177-X.
33. Mariette X, Förger F, Abraham B, et al. Lack of placental transfer of certolizumab pegol during pregnancy: results from CRIB, a prospective, postmarketing, pharmacokinetic study. Ann Rheum Dis. 2018 Feb;77(2):228-33.

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