Subcutaneous Immunotherapy with a Depigmented Polymerized Birch Pollen Extract – A New Therapeutic Option for Patients with Atopic Dermatitis

Background: Birch pollen is an important outdoor allergen able to aggravate symptoms in atopic dermatitis (AD). Specific immunotherapy (SIT), an established procedure for allergic airway diseases, might also represent an attractive therapeutic option for the causal treatment of allergen-triggered cutaneous symptoms in these patients. Studies with house dust mite SIT have already shown beneficial effects in AD patients, whereas the safety and efficacy of SIT with birch pollen extract in AD patients have not been studied so far. The aim of this study was to evaluate for the first time the safety and efficacy of SIT with a depigmented polymerized birch pollen extract in AD patients. Methods: Fifty-five adult patients with moderate-to-severe AD and clinically relevant sensitization to birch pollen received SIT for 12 weeks. SIT was continued during birch pollen season. The assessment of safety, the total SCORAD value, and the Dermatology Life Quality Index (DLQI) were evaluated. Results: The median total SCORAD value was reduced by 34% (p < 0.001) during the course of treatment and the mean DLQI improved by 49% (p < 0.001) despite strong simultaneous birch pollen exposure. Eight patients (14.5%) developed systemic reactions and 19 patients (34.5%) developed local reactions which were of mild intensity in most cases. No patient discontinued the study prematurely due to adverse drug reactions. Coseasonal treatment was well tolerated. Conclusion: SIT with a depigmented polymerized birch pollen extract leads to significant improvement of the SCORAD value and the DLQI in patients suffering from moderate-to-severe AD sensitized to birch pollen.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

Manifestation of palmoplantar pustulosis during or after infliximab therapy for plaque-type psoriasis: report on five cases

Infliximab is a monoclonal antibody directed against TNF-α. It has been approved for use in rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriatic arthritis and plaque-type psoriasis. In case reports, positive effects on pustular variants of psoriasis have also been reported. However, paradoxically, manifestation of pustular psoriasis and plaque-type psoriasis has been reported in patients treated with TNF antagonists including infliximab for other indications. Here, we report on 5 patients with chronic plaque-type psoriasis who developed palmoplantar pustulosis during or after discontinuation of infliximab therapy. In two of the five cases, manifestation of palmoplantar pustulosis was not accompanied by worsening of plaque-type psoriasis. Possibly, site-specific factors or a differential contribution of immunological processes modulated by TNF inhibitors to palmoplantar pustulosis and plaque-type psoriasis may have played a role

Dupilumab shows long-term safety and efficacy in patients with moderate to severe atopic dermatitis enrolled in a phase 3 open-label extension study

BACKGROUND: Significant unmet need exists for long-term treatment of moderate to severe atopic dermatitis (AD). OBJECTIVE: To assess the long-term safety and efficacy of dupilumab in patients with AD. METHODS: This ongoing, multicenter, open-label extension study (NCT01949311) evaluated long-term dupilumab treatment in adults who had previously participated in phase 1 through 3 clinical trials of dupilumab for AD. This analysis examined patients given 300 mg dupilumab weekly for up to 76 weeks at data cutoff (April 2016). Safety was the primary outcome; efficacy was also evaluated. RESULTS: Of 1491 enrolled patients (1042.9 patient-years), 92.9% were receiving treatment at cutoff. The safety profile was consistent with previously reported trials (420.4 adverse events/100 patient-years and 8.5 serious adverse events/100 patient-years), with no new safety signals; common adverse events included nasopharyngitis, conjunctivitis, and injection-site reactions. Sustained improvement was seen up to 76 weeks in all efficacy outcomes, including measures of skin inflammation, pruritus, and quality of life. LIMITATIONS: Lack of control arm, limited number of patients with 76 weeks or longer of treatment (median follow-up, 24 weeks), and patients not receiving the approved dose regimen of 300 mg every 2 weeks. CONCLUSION: The safety and efficacy profile from this study supports the role of dupilumab as continuous long-term treatment for patients with moderate to severe AD

Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis

BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known

Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial

Background: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has shown superior efficacy to etanercept with similar safety in moderate to severe plaque psoriasis (FIXTURE study). Objective: We sought to directly compare efficacy and safety of secukinumab versus ustekinumab. Methods: In this 52-week, double-blind study (NCT02074982), 676 subjects were randomized 1:1 to subcutaneous injection of secukinumab 300 mg or ustekinumab per label. Primary end point was 90% or more improvement from baseline Psoriasis Area and Severity Index (PASI) score (PASI 90) at week 16. Results: Secukinumab (79.0%) was superior to ustekinumab (57.6%) as assessed by PASI 90 response at week 16 (P &lt; .0001). The 100% improvement from baseline PASI score at week 16 was also significantly greater with secukinumab (44.3%) than ustekinumab (28.4%) (P &lt; .0001). The 75% or more improvement from baseline PASI score at week 4 was superior for secukinumab (50.0%) versus ustekinumab (20.6%) (P&lt; .0001). Percentage of subjects with the Dermatology Life Quality Index score 0/1 (week 16) was significantly higher with secukinumab (71.9%) than ustekinumab (57.4%) (P &lt; .0001). The safety profile of secukinumab was comparable with ustekinumab and consistent with pivotal phase III secukinumab studies. Limitations: The study was not placebo-controlled and of short-term duration. Conclusions: Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe psoriasis and improving health-related quality of life with a comparable safety profile over 16 weeks

GRAPPA Fellows Symposium Adjacent to the European Academy of Dermatology and Venereology (EADV) Congress, Istanbul, 2013: a meeting report

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) organized its second Fellows Symposium adjacent to the European Academy of Dermatology and Venereology (EADV) congress in Istanbul in October 2013. Wolf-Henning Boehncke from Geneva, Brian Kirby from Dublin, and Diamant Thaci from Lübeck formed the faculty. The 9 best-ranked abstracts submitted to this symposium were presented and discussed in detail. Five abstracts focused on comorbidities in patients with psoriasis or psoriatic arthritis; summaries of all abstracts are included herein

Calcipotriol solution for the treatment of scalp psoriasis: evaluation of efficacy, safety and acceptance in 3,396 patients

BACKGROUND: Psoriasis of the scalp is a very common disease, cosmetically disturbing and therapeutically difficult to manage. OBJECTIVE: The aim of our study was to investigate the efficacy, safety and cosmetic acceptance of calcipotriol solution in a large number of patients with mild to moderate scalp psoriasis and to compare this treatment with previous therapies used. METHODS: In this multicentre prospective observational cohort study 3,396 patients were treated with calcipotriol solution (50 microg/ml) twice daily over an 8-week period either alone or in combination with other treatments. The psoriasis scalp severity index (PSSI) and investigator/patient global assessment were used for the evaluation of clinical response. RESULTS: All psoriasis severity parameters measured were reduced with a significant decrease in PSSI scores from 18.4 to 5.6 after 8 weeks of therapy (p < 0.001). About 80% of the patients showed very good or good clinical improvement. Combination of calcipotriol solution with other treatment modalities e.g. corticosteroids or salicylic acid, showed an increased treatment response. In only 2.4% of the patients side effects occurred (e.g. irritation). CONCLUSION: Calcipotriol solution is an effective, safe, well-tolerated and cosmetically acceptable treatment modality. By patients and physicians, this treatment was found to be a valuable supplement to previously available and established treatments for scalp psoriasis

Treatment of psoriasis with alefacept in patients with hepatitis C infection: a report of two cases

Alefacept is a fully human fusion protein for use in adult patients with moderate to severe chronic plaque psoriasis. Its dual mechanism of action involves inhibition of T-cell activation and selective reduction of memory T cells. We report the clinical course of two patients with hepatitis C virus (HCV) infection who have received alefacept for psoriasis. Consistent with its mechanism of action, administration of alefacept led to transient decreases in CD4+ and CD8+ T-cell counts. However, these reductions were not associated with an increase in HCV viral load or exacerbation of infection. Liver enzymes remained stable throughout the treatment and follow-up periods. Alefacept has a selective mechanism of action that specifically targets memory T cells and this selectivity may account for its safety and tolerability in patients with hepatitis

Efficacy of dexpanthenol in skin protection against irritation: a double-blind, placebo-controlled study

Dexpanthenol is popular in treating various dermatoses and in skin care, but few controlled clinical trials have been performed. We investigated the efficacy of dexpanthenol in skin protection against irritation in a randomized, prospective, double-blind, placebo-controlled study. 25 healthy volunteers (age 18-45 years) were treated for the inner aspect of both forearms with either Bepanthol Handbalsam containing 5% dexpanthenol or placebo x2 daily for 26 days. From day 15-22, sodium lauryl sulfate (SLS) 2% was applied to these areas x2 daily. Documentation comprised sebumetry, corneometry, pH value and clinical appearance (photographs). 21 volunteers completed the study, 3 were excluded because of non-compliance and 1 experienced a non-study-related, severe, adverse event. Only corneometry yielded a statistically significant difference, with decreased values following SLS challenge at the placebo sites (P < 0.05). Intraindividual comparisons showed superior results at the dexpanthenol-treated sites in 11 cases and in only 1 case at the placebo site. 6 volunteers experienced an irritant contact dermatitis, with more severe symptoms at the placebo site in 5 cases. In conclusion, dexpanthenol exhibits protective effects against skin irritation. The initiation of a study to evaluate the efficacy of dexpanthenol in preventing irritant occupational contact dermatitis under real workplace conditions is validated

Microdialysis documents changes in the micromilieu of psoriatic plaques under continuous systemic therapy

Microdialysis is a novel technique suitable to analyse soluble mediators in the skin compartment. We applied this methodical approach to monitor changes in the micromilieu of psoriatic plaques under therapy. Tissue fluid was collected from lesional and non-lesional skin of three patients with severe plaque-type psoriasis prior to as well as after 12 weeks of continuous oral therapy with fumaric acid esters. Concentrations of a spectrum of cytokines and adipokines were measured using a commercial fluorescent bead immunoassay. The procedure was well tolerated even without local anaesthesia. Prior to initiation of therapy, we found elevated levels for IL-2, IL-6, IL-18, IL-23, and resistin in lesional versus non-lesional skin, whereas adiponectin levels were higher in non-lesional skin. All patients showed significant clinical improvement under treatment, paralleled by reduced concentrations of IL-6, IL-18, IL-23, and resistin, but not IL-2 and adiponectin in lesional skin. Thus, we were able to demonstrate through microdialysis a shift in the micromilieu of psoriatic plaques, characterized by reduced levels of pro-inflammatory mediators in three patients under effective systemic anti-inflammatory therapy with fumaric acid esters. Our observations need to be confirmed by larger studies. This approach is limited by practical aspects as it is very time-consuming, but suitable to directly explore pathomechanisms causing the psoriatic phenotype in general and insulin resistance in the skin compartment in particular