Long-term follow-up of 22 psoriatic patients treated with ixekizumab after failure of secukinumab

Switching of biologic agents in treatment of plaque psoriasis is a common strategy. Only a few studies are available on switching between IL17A-blockers. In a retrospective study, we identified 22 psoriasis patients who, after failing secukinumab as a first IL17A-blocker received ixekizumab with an observation period of at least 24 weeks. At last observation 10/22 patients had a good response (PASI75 or PASI<3) using ixekizumab therapy. None of five patients with primary non-response to secukinumab reached a good, durable response to ixekizumab. In conclusion, ixekizumab appears to be a therapeutic option as a second IL17A-blocker in psoriasis patients who did not show a primary non-response to secukinumab

Analysis of a functional serotonin transporter promoter polymorphism in psoriasis vulgaris

Serotonin is a monoamine acting as a neuromediator in the central and peripheral nervous system. Recently, serotonin has also been shown to influence T- and B-cell function. The serotonin transporter is central in the regulation of the serotonergic system and widely expressed on cells of the immune system. A functional length polymorphism in the promoter of the serotonin transporter gene (5-HTTLPR) has been implicated in the genetic background of depression. Psoriasis is a complex disease with a polygenetic inheritance. In light of the role of T-cell mediated inflammation in psoriasis and the increased prevalence of depression in psoriatic patients, we analyzed the 5-HTTLPR polymorphism in 309 patients with psoriasis vulgaris and 315 healthy control individuals. No significant differences in genotype distribution and allele frequencies were found. There was also no difference in the score of the Hamilton Rating Scale for Depression in patients with psoriasis (n = 137) characterized by carriage of different 5-HTTLPR genotypes. These findings argue against a major contribution of the 5-HTTLPR polymorphism to psoriasis susceptibility and the occurrence of depressive symptoms among psoriatic patients

Polymorphisms in the ATG16L1 Gene are associated with psoriasis vulgaris

Letter to the Edito

Balanced carving turns in alpine skiing

In this paper, we analyse the model of pure carving turns in alpine skiing and snowboarding based on the usual assumption of approximate balance between forces and torques acting on the skier during the turn. The approximation of torque balance yields both lower and upper limits on the skier speed, which depend only on the sidecut radius of skis and the slope gradient. We use the model to simulate carving runs on slopes of constant gradient and find that pure carving is possible only on slopes of relatively small gradient, with the critical slope angle in the range of 8∘−20∘. The exact value depends mostly on the coefficient of snow friction and to a lesser degree on the sidecut radius of skis. Comparison with the practice of ski racing shows that the upper speed limit and the related upper limit on the slope gradient set by the model are too restrictive and so must be the assumption of torque balance used in the model. A more advanced theory is needed

Venlafaxine’s therapeutic reference range in the treatment of depression revised: a systematic review and meta-analysis

Introduction The selective serotonin and norepinephrine reuptake inhibitor venlafaxine is among the most prescribed antidepressant drugs worldwide and, according to guidelines, its dose titration should be guided by drug-level monitoring of its active moiety (AM) which consists of venlafaxine (VEN) plus active metabolite O-desmethylvenlafaxine (ODV). This indication of therapeutic drug monitoring (TDM), however, assumes a clear concentration/effect relationship for a drug, which for VEN has not been systematically explored yet. Objectives We performed a systematic review and meta-analysis to investigate the relationship between blood levels, efficacy, and adverse reactions in order to suggest an optimal target concentration range for VEN oral formulations for the treatment of depression. Methods Four databases (MEDLINE (PubMed), PsycINFO, Web of Science Core Collection, and Cochrane Library) were systematically searched in March 2022 for relevant articles according to a previously published protocol. Reviewers independently screened references and performed data extraction and critical appraisal. Results High-quality randomized controlled trials investigating concentration/efficacy relationships and studies using a placebo lead-in phase were not found. Sixty-eight articles, consisting mostly of naturalistic TDM studies or small noncontrolled studies, met the eligibility criteria. Of them, five cohort studies reported a positive correlation between blood levels and antidepressant effects after VEN treatment. Our meta-analyses showed (i) higher AM and (ii) higher ODV concentrations in patients responding to VEN treatment when compared to non-responders (n = 360, k = 5). AM concentration-dependent occurrence of tremor was reported in one study. We found a linear relationship between daily dose and AM concentration within guideline recommended doses (75–225 mg/day). The population-based concentration ranges (25–75% interquartile) among 11 studies (n = 3200) using flexible dosing were (i) 225–450 ng/ml for the AM and (ii) 144–302 ng/ml for ODV. One PET study reported an occupancy of 80% serotonin transporters for ODV serum levels above 85 ng/ml. Based on our findings, we propose a therapeutic reference range for AM of 140–600 ng/ml. Conclusion VEN TDM within a range of 140 to 600 ng/ml (AM) will increase the probability of response in nonresponders. A titration within the proposed reference range is recommended in case of non-response at lower drug concentrations as a consequence of VEN’s dual mechanism of action via combined serotonin and norepinephrine reuptake inhibition. Drug titration towards higher concentrations will, however, increase the risk for ADRs, in particular with supratherapeutic drug concentrations

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