Guselkumab: the First Selective IL-23 Inhibitor for Active Psoriatic Arthritis in Adults.

INTRODUCTION: Guselkumab is a subcutaneously administered human monoclonal antibody, selectively blocking IL-23 through binding to its p19 subunit. It was initially approved for the treatment of patients with moderate-to-severe plaque-psoriasis who are candidates for systemic therapy or phototherapy. Pubmed and Embase databases were searched for publications, using the following search terms: psoriasis, psoriatic arthritis, guselkumab, risankizumab, tildrakizumab, p19, interleukin 23, guidelines, treatment recommendations, DISCOVER, ECLIPSE, and VOYAGE. AREAS COVERED: Accumulating evidence suggests that the IL-23/Th17 pathway is important in the pathogenesis of both psoriasis and psoriatic arthritis. Following a successful development program in psoriasis, guselkumab was evaluated for its efficacy and safety in psoriatic arthritis in a comprehensive clinical trial program, comprising one phase-2 study and two phase-3 studies (DISCOVER-1 and -2). Complementary data on pharmacokinetics and safety exist from pre-clinical experiments and pooled analyses from two long-term studies in psoriasis (VOYAGE-1 and -2). Based on the DISCOVER-1 and -2 data, guselkumab was approved by the FDA for the treatment of active psoriatic arthritis in 2020. EXPERT OPINION: Guselkumab is the first selective IL-23 inhibitor approved to treat adults with active psoriatic arthritis, broadening therapeutic options in the field through a novel mode of action.

[Fumarates - far more than a dietary supplement]. / Dermatologie Fumarates ­ bien plus qu'un additif alimentaire.

Fumaric acid has an important role in the citric acid cycle. Its esters were first used by a German chemist to treat his own psoriasis, hypothesizing that the disease may be related to disturbances in this very cycle. Meanwhile, the mechanisms underlying its anti-inflammatory efficacy are much better understood. A monosubstance derived from the mix of esters used originally is now being authorized for treating multiple sclerosis, and in 2017 dimethylfumaric acid ester became a globally available option to treat psoriasis. This very practical therapeutic will most likely become quite popular amongst patients. Therefore, general practitioners might need to familiarize themselves with the profile of this drug, including its potential risks and some very rare but potentially important adverse effects.

L'acide fumarique joue un rôle important dans le cycle de Krebs. Ses esters ont été utilisés pour la première fois par un chimiste allemand pour traiter son propre psoriasis dans l'hypothèse d'une implication du cycle de Krebs. Depuis, les mécanismes anti-inflammatoires des esters d'acide fumarique ont été mieux décrits. Une mono-substance dérivée du mélange d'esters original est désormais autorisée pour traiter la sclérose en plaques. En 2017, le diméthylfumarate a été ainsi reconnu globalement comme une option thérapeutique pour le psoriasis. Très pratique, ce médicament deviendra probablement très populaire chez les patients. Pour cette raison, les médecins généralistes devraient se familiariser avec son profil pharmacologique, y compris ses risques potentiels et certains effets indésirables rares mais potentiellement dangereux.

Platelet P-selectin reflects a state of cutaneous inflammation: possible application to monitor treatment efficacy in psoriasis.

Haemostasis-maintaining platelets are also recognized as important modulators in the regulation of immune response. Activated platelets expressing P-selectin (CD62P) are involved in the extravasation of leucocytes. This study evaluated platelet P-selectin expression as a biomarker for cutaneous inflammation. P-selectin expression was assessed by flow cytometry in 147 successive patients suffering from an inflammatory or infectious skin condition at the day of admission for in-patient treatment as well as a day prior to demission. Forty-one patients admitted for allergy testing served as controls. A commercially available ELISA was used in 17 patients to determine soluble P-selectin in the plasma. In patients with psoriasis, the Psoriasis Area and Severity Index (PASI) was documented as a measure for disease severity. We observed a significant increase in platelet P-selectin expression in patients with inflammatory or infectious disorders, when compared to the control group (3,01% vs. 1,46%; P < 0.000001). Successful treatment resulted in a significant decrease in P-selectin expression to the level of the control group. In the case of psoriasis (n = 47), we found highly significant correlation between P-selectin and PASI (r = 0.51; P < 0.000001), as well as between the change in the PASI and the change in P-selectin expression (r = 0.4; P = 0.006). Platelet P-selectin expression as determined by flow cytometry correlated well with the results of soluble P-selectin, determined by ELISA (r = 0.63; P < 0.01). Thus, platelet P-selectin expression may be used as an efficacy biomarker to monitor treatment success in psoriasis. As platelet P-selectin correlates with soluble P-selectin in patient plasma, which can be measured by ELISA, the latter is feasible also for routine use.

Biologic therapies for psoriasis. A systematic review.

Alefacept, efalizumab, etanercept, and infliximab are currently approved for the treatment of adults with moderate to severe plaque psoriasis, and phase 3 trials for adalimumab are ongoing. The high level of evidence from large randomized, double-blind, placebo-controlled clinical studies for each of these biologics allows high-grade recommendations and helps define uncertainties, one of which is longterm safety. For tumor necrosis factor-a blocking agents, safety profiles are available from clinical experience in other indications. In general, biologics are safe and effective in the treatment of psoriasis, with potential to address unmet medical needs. Their distinct profiles allow dermatologists to match the biologic agent to individual characteristics of patients who are candidates for systemic therapy or phototherapy. In this evidence-based review of the literature, we assess the effects on psoriasis of induction therapy with 5 biologics and provide preliminary treatment guidelines.

Narrowband UVB and cream psoralen-UVA combination therapy for plaque-type psoriasis.

BACKGROUND: Psoralen-UVA (PUVA) and narrowband UVB (311-nm) therapy are considered to be first-line phototherapies for patients with moderate to severe psoriasis. To reduce side effects as a result of systemic resorption of psoralens, topical PUVA therapies have been developed and proven to be effective in the treatment of psoriasis. OBJECTIVE: We sought to evaluate the combination therapy of narrowband UVB plus cream PUVA on selected psoriatic plaques compared with narrowband UVB or cream PUVA alone. METHODS: A total of 30 patients (Psoriasis Area and Severity Index score of 8-15) were included in the randomized study. The combination therapy consisting of narrowband UVB whole-body irradiation followed by cream PUVA therapy for selected psoriatic plaques was evaluated in 10 patients with chronic plaque-stage psoriasis. For comparison, the therapeutic efficacy, number of treatments, and cumulative UV doses until remission (Psoriasis Area and Severity Index score < 4) of cream PUVA therapy or narrowband UVB alone was determined in 10 patients, respectively. RESULTS: Both monotherapies induced clearance of psoriatic lesions in all patients within 5 to 7 weeks. Mean number of treatments for cream PUVA was 24 +/- 5; for narrowband UVB was 21 +/- 3. The mean cumulative UVA dose was 45.0 +/- 16.3 J/cm(2) and the mean cumulative UVB dose was 17.1 +/- 4.1 J/cm(2). Combination therapy resulted in complete clearance of lesions in all patients after 3 to 4 weeks. Mean number of treatment was 14 +/- 2, mean cumulative UVA dose was 18.7 +/- 4.7 J/cm(2), and mean cumulative UVB dose was 8.2 +/- 3.3 J/cm(2). The number of treatments (P <.001, analysis of variance), UVA dose (P <.001, t test), and UVB dose (P <.001, t test) were significantly reduced compared with both monotherapies. CONCLUSIONS: Our results indicate that a combination therapy of narrowband UVB plus cream PUVA appears to have a significantly higher efficacy compared with either monotherapy. The cumulative UV doses were significantly lower in the combination therapy. We conclude that cream PUVA can be used in addition to narrowband UVB for areas that tend to clear less quickly than the rest of the body.

Narrowband UV-B phototherapy in the treatment of cutaneous graft versus host disease.

Graft versus host disease (GVHD) is an important problem following allogenic bone marrow transplantation (BMT). The beneficial effects of photochemotherapy with psoralens plus UVA irradiation (PUVA) have been described repeatedly; however, PUVA is limited by a wide range of unwanted effects. A novel improved form of UV-B phototherapy, narrowband UV-B, has been proven to be very effective in T-cell mediated dermatoses. Therefore, we investigated the effect of narrowband UV-B phototherapy (5 times per week) in 10 patients with cutaneous GVHD (grade 2-3) resistant to standard immunosuppressive drugs. It was tolerated well by all patients, and no side effects were observed. Skin lesions showed complete clearance in 7 out of 10 patients within 3 to 5 weeks. 3 patients showed significant improvement of GVHD. We suggest that narrowband UV-B phototherapy is a nonaggressive treatment that may benefit patients with cutaneous GVHD who already take high doses of immunosuppressive drugs.