Sustained resolution of nail psoriasis through five years with ixekizumab
Today's report also covers comorbidities in generalized pustular psoriasis patients, systemic treatments affecting new onset AD and psoriasis, and more (1,800 words, 9 minutes, 10 seconds)
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Good morning and welcome to the fifth issue of Special Reports: Skin Spectrum Weekly presents “Vender on Psoriasis.” This series is based on Dr. Vender’s popular column appearing in each edition of The Chronicle of Skin & Allergy, which offers expert commentary and opinions on current clinical developments in PsO. We’d love to get your feedback and suggestions and invite you to be in touch. Please write to us at email@example.com
Sustained resolution of nail psoriasis through five years with ixekizumab
This post-hoc analysis from UNCOVER-3 investigated the effect of continuous treatment with the interleukin-17A inhibitor ixekizumab on nail psoriasis. The results show that approximately six out of 10 patients achieved and maintained clearance of their fingernail psoriasis through 264 weeks, regardless of the severity of nail psoriasis, according to Acta Dermato Venereologica (Oct. 10, 2022).
Parameters at baseline included 385 patients who received ixekizumab and had either any degree of nail psoriasis (Nail Psoriasis Severity Index [NAPSI] >=1) or significant nail psoriasis (fingernail NAPSI ≥16 and ≥4 fingernails involved). Efficacy outcomes reported through week 264 included the mean percentage improvements from baseline in NAPSI score and the proportion of patients achieving nail psoriasis resolution (NAPSI=0). In UNCOVER-3, 56.9% (219/385) of patients had nail psoriasis at baseline; of those, 61.2% (134/219) had significant nail psoriasis. According to the authors, at week 60 a total of 66.9% and 59.1% of patients with baseline nail psoriasis and significant baseline nail psoriasis, respectively, reported complete clearance of nail psoriasis, which was sustained through week 264. This analysis demonstrates that continuous treatment with ixekizumab in adult patients with moderate-to-severe-psoriasis through 264 weeks was associated with improvements and clearance of fingernail psoriasis, irrespective of the severity of nail psoriasis at baseline.
The authors report that these findings support the long-term efficacy of ixekizumab for the treatment of nail psoriasis, which is a chronic, difficult-to-treat, and often debilitating condition with a high disease burden and considerable impairment in a patient’s quality of life.
Comment: Nail psoriasis is extremely difficult to treat. The appendage only has a blood supply to the matrix and nail bed making it difficult for effective medications to reach the area of difficulty. Unfortunately, topical therapies do not help for nail psoriasis. Injecting the nail matrix with a corticosteroid is extremely painful and can lead to secondary infection. In addition, traditional systemic therapies rarely improve nail psoriasis and some can even make it worse, such as acitretin that can soften the nails.
Since biologics have been available for psoriasis patients, the general correlation is that the efficacy in nails is no better than it is in improving the skin. For example, as good as the biologic works for the skin is as good as it will work for the nails. So far, no biologic has stood out as the best for nail psoriasis treatment. This study, however, is encouraging because there is a great chance for improvement when using an effective and safe biologic such as ixekizumab. Most clinical studies use this post analysis to determine improvement of nails. Secukinumab has performed its own study with respect to nail psoriasis showing results similar to this study.
Comorbidities in patients with generalized pustular psoriasis (GPP)
This population-based register study used the Swedish National Patient Register (NPR) to study the comorbidity profile of GPP compared to the general population and patients with psoriasis vulgaris (PV). GPP has higher rates of Crohn's disease, type 2 diabetes, peptic ulcer disease, celiac disease, sinusitis, and stroke, although the researchers noted some observed associations have a high degree of uncertainty.
The researchers identified 1,093 GPP cases during 2004-2015. These cases were matched (1:3) to PV controls (without GPP), and (1:5) to general population controls. The mean age in all study groups was 56 years and 60% were female. The investigators report that among the GPP cases, 53% had also PV. A subgroup analysis including only GPP cases without PV (n=514) and corresponding PV controls (n=1,518) was also performed, according to the Journal of the American Academy of Dermatology (Oct. 10, 2022). In general, the study indicates a higher comorbidity burden in GPP in Sweden compared to the general population and PV.
Among GPP cases, 70% had any of the noted comorbidities, compared to 46% of the general population controls and 63% of PV controls. The most prevalent conditions in GPP were hypertension, psoriatic arthritis, type 2 diabetes, and hyperlipidemia. GPP cases had significantly higher odds ratios (ORs) for any of the selected comorbidities compared to both the general population controls and PV controls. The largest significant differences between GPP cases and general population controls were for allergic contact dermatitis, Crohn’s disease, non-alcoholic fatty liver disease, nephritic non-hypertensive disease, and obesity. Compared to PV controls, the largest differences were for nephritic non-hypertensive disease, Crohn’s disease, chronic renal failure, diabetes type 1 and 2, peptic ulcer disease, and psoriatic arthritis. Among these, Crohn’s disease, diabetes type 2, and peptic ulcer disease remained significantly elevated in subgroup analyses. Also, excluding GPP cases with concurrent PV increased the odds for celiac disease (OR:2.82, CI:1.05-7.56), sinusitis (OR:2.57; CI: 1.37-4.83), and stroke (OR:1.72; 95% CI: 1.14-2.59).
The researchers concluded there is a higher comorbidity burden in GPP in Sweden compared to both the general population and PV.
Comment: Generalized pustular psoriasis, also known as GPP, is a severe condition that consists of red sterile pustules with pustular plaques. It can be associated with increased white cell count, high markers of inflammation such as CRP, fatigue, malaise, fevers, and extreme discomfort. The course is extremely unpredictable with lows and highs and flares and remissions. It is associated with strong genetic factors such as IL 36 RN. Plaque psoriasis already has many associated comorbidities however, as shown in this study, GPP has even more comorbidities of significance such as stroke, sinusitis, and, interestingly, celiac disease. Celiac disease is uncommon in psoriasis and has its own skin condition known as dermatitis herpetiformis. Treating these patients includes pain reduction and to look for other medical conditions such as cardiac complications, renal complications, and respiratory problems. Luckily, new treatments targeting the IL 36 pathway such as spesolimab, not yet approved in Canada, will be a great benefit for patient suffering from this horrible disorder.
New onset atopic dermatitis and psoriasis in the same patients under biologic treatments: The role of systemic treatments as a possible trigger
Typically, atopic dermatitis (AD) and psoriasis (PsO) are reported as two diseases that do not coexist in the same patient because that would require the activation of opposing inflammatory pathways, specifically Th2 in AD and Th1 in PsO. However, some reports have emerged that highlight how AD and PsO may coexist in the same patient or develop consequently, according to Dermatologic Therapy (Sep. 11, 2022).
Researchers from Milan identified 12 patients who developed new AD or PsO. Eight patients (n=8; 3M:5F) with a previous diagnosis of PsO developed AD (mean time of onset, 71.5 months). Of these eight patients, four were being treated with ustekinumab, one with ixekizumab, two with adalimumab, and one with guselkumab. The new onset AD cases were treated topically, except for one case treated with dupilumab.
Conversely, four patients with baseline AD developed PsO with a mean time of onset of 25 months. Two of the patients who developed AD were treated with dupilumab, while the other two patients were treated with topicals.
The study authors note that both conditions are chronic relapsing inflammatory diseases, which may require numerous specialist check-ups and various topical and systemic treatments. They report that AD and PsO are not mutually exclusive diseases, and clinicians should carefully evaluate any changes in these patients to reach a correct diagnosis and offer appropriate treatments.
Comment: This concept of two opposite diseases occurring in one patient is extremely interesting. As noted in this study, a clinician would not expect this whatsoever when treating psoriasis. We often hear patients say that they had eczema as a baby and then develop psoriasis. We very rarely hear that they had psoriasis as a child and then developed eczema as adults. However, the biologics may be changing the course of disease by modifying the pathways that individuals experience when developing specific diseases. It seems that the typical immunological rules no longer apply due to this immune modulation. The important point is that if a patient calls and says that their psoriasis or dermatitis is flaring, and adjustments are made verbally without seeing the exact eruption or flare that has occurred, then a clinician could miss this paradoxical conversion to a different or opposite disease state. Changes should be assessed visually with close physical examination and potential biopsies to determine the new disease eruption. Unfortunately, a diagnosis of psoriasisiform dermatitis often is reported in pathology reports which leads to management confusion. One would rarely see the diagnoses of dermatitic psoriasis. However, this study is extremely important showing that these two diseases can coexist in one patient or even change clinical expression to the other.
If you find the contents of this newsletter interesting, please check out the Vender on Psoriasis podcast. It’s available at Apple iTunes, Stitcher, Spotify, or wherever you get your podcasts.
Dr. Ron Vender is a Hamilton-based certified dermatologist with 31 years of clinical practice experience and over 100 clinical trials in psoriasis. He is founder and director of Venderm Innovations in Psoriasis, a centre of excellence for Psoriasis offering a comprehensive management solution for individuals with psoriasis.
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