47 research outputs found
Therapieansprechen der palmoplantaren Pustulose auf Upadacitinib: eine Fallserie von fünf Patienten
No full textExpression of CD152 (CTLA-4) on T lymphocytes in melanoma and in blood after hyperthermia
No full textIm ersten Teil dieser Arbeit wurde gezeigt, dass ein Großteil der tumorinfiltrierden Lymphozyten (TIL) bei Primärmelanomen hohe Expressionswerte des anti-inflammatorischen T-Zellmarkers CTLA-4 aufweist. Der in klinischen Studien bereits gezeigte stimulierende Effekt für die Tumorantwort durch die Blockade von CTLA-4 mittels monoklonaler Antikörper mag daher zumindest teilweise durch die Reaktivierung dieser TIL bedingt sein. Ob es sich bei den beschriebenen TIL um regulatorische T-Zellen (Treg) handelt, ist noch zu zeigen.
Im zweiten Teil dieser Arbeit wurde die CTLA-4-Expression von PBL (periphere Blutlymphozyten) von Hyperthermie-behandelten Tumorpatienten gemessen. Dabei zeigte sich ein Expressionsmaximum am sechsten Tag nach Hyperthermie. Eine zusätzliche therapeutische CTLA-4-AK-Gabe nach Hyperthermie sollte daher an diesem Tag oder früher erfolgen, um einen größtmöglichen therapeutischen Nutzen zu erzeugen.
Im dritten Teil dieser Arbeit wurde ein Computer-gestütztes Messsystem für die CTLA-4-Expression von PBL etabliert, welche eine Alternative zur bislang manuellen Auszählung darstellt.We could show that a major part of tumor infiltrating lymphocytes (TIL) of primary melanoma shows a high expression of the anti-inflammatory molecule CTLA-4. The (by clinical studies well-known known) immunostimulatory effect of monoclonal antibodies against CTLA-4 might be (at least partly) explained by reactivation of these TIL. If the decribed TIL are regulatory T cells (Treg) has still to be shown.
Furthermore we measured the CTLA-4 expression of periphery blood lymphocytes (PBL) of hyperthermia treated tumor patients. We could detect a peak of CTLA-4 expression at day 6 after hyperthermia. If an additional CTLA-4 antibody therapy was planned in hyperthermia patients, we consequently suggest the application at day 6 after hyperthermia to reach best therapeutic results.
Finally we established a computer based measurement system for CTLA-4 expression on PBL. That system might be an alternative to the manual method
Efficacy and safety of topical tacrolimus microemulsion applied twice daily in patients with mild to moderate scalp psoriasis
No full textIntroduction:
Involvement of the scalp is common in psoriasis and severely affects the quality of life of those affected. It is difficult to treat and places special demands on the galenics of a drug formulation. Tacrolimus is a calcineurin inhibitor and is approved as an ointment formulation for the treatment of atopic dermatitis. The efficacy and safety of topically applied tacrolimus have also been studied and proven for psoriasis. However, no proprietary pharmaceutical product is currently approved for this indication.
Methods:
A multicenter, double-blind, vehicle-controlled phase 3 study was conducted to evaluate the efficacy and safety of 0.1% tacrolimus microemulsion when applied topically twice daily in 128 patients independently of sex with scalp psoriasis.
Results:
The primary efficacy analysis showed a scalp Investigator Global Assessment (s-IGA) of 0 (absence of disease) or 1 (very mild disease) at 8 weeks in 28.6% of subjects in the tacrolimus group, indicating a significantly better response (p = 0.0476, chi-square test) versus 12.7% of subjects in the placebo group (difference of 15.9%-points). The Dermatology Life Quality Index (DLQI) improved over time and was more pronounced in the group treated with tacrolimus-containing microemulsion than in the placebo group, but showed no statistically significant difference after 8 weeks of use (p = 0.193, ANCOVA). The safety analysis revealed no evidence of cutaneous side effects other than those known. Toxicologically relevant serum levels of tacrolimus could be excluded.
Conclusion:
The study data show that 0.1% tacrolimus microemulsion has good efficacy and safety in the treatment of scalp psoriasis
Brodalumab Versus Guselkumab in Patients with Moderate-to-Severe Psoriasis with an Inadequate Response to Ustekinumab: A Randomized, Multicenter, Double-Blind Phase 4 Trial (COBRA)
No full textAbstract Introduction Despite improved treatment options for plaque psoriasis within the last decades, some patients still have an inadequate response to treatment. Direct clinical evaluation between therapies used after biologic failure could facilitate physicians’ choice of treatment. Methods COBRA (NCT04533737) was a randomized (1:1), blinded (patient and assessor), 28-week, active-comparator trial conducted in Europe from December 2020 to December 2022. The objective was to compare the efficacy and safety of brodalumab versus guselkumab in adults with moderate-to-severe plaque psoriasis and inadequate response to ustekinumab. Patients received either brodalumab 210 mg or guselkumab 100 mg. The primary [having Psoriasis Area and Severity Index (PASI)-100 response at week 16] and key secondary (time to PASI-100 response) endpoints were tested in a fixed sequence. Results Due to delays and enrollment challenges, recruitment was terminated with 113 patients enrolled of 240 planned. The proportion of patients having PASI-100 at week 16 for brodalumab was 53.4% compared with 35.9% for guselkumab [odds ratio (OR) 2.05; 95% confidence interval (CI) 0.95, 4.44; p = 0.069]. As this was not statistically significant, the hierarchical testing procedure was stopped. All other secondary PASI endpoints had nominal p-values below 0.05 in favor of brodalumab. In the time to PASI response analyses, brodalumab separated from guselkumab in estimated cumulative incidence of patients achieving a response from week 2 onward, suggesting fast onset of action with brodalumab. Quality of life measures improved in both treatment groups. The safety findings were consistent with the known safety profiles. Conclusions Brodalumab showed a tendency toward better and earlier effect than guselkumab in patients who had failed ustekinumab. Thus, this trial provides important information in assisting physicians in their choice of therapy for patients who have failed their prior anti-interleukin (IL)-12/23 treatment. Trial Registration ClinicalTrials.gov identifier NCT04533737
The option of compassionate use in metastatic melanoma â way out of a therapeutic dilemma?
No full textA Comparative Analysis of the Predictors, Extent and Impacts of Self-stigma in Patients with Psoriasis and Atopic Dermatitis
No full textThe impact of dermatological diseases goes beyond symptoms and often includes psychosocial burden. Self-stigmatization plays a key role in this relationship and was compared in patients with psoriasis and atopic dermatitis to evaluate the validity of cross-disease stigmatization models. In total, 101 patients per indication were included in this cross-sectional study. Besides sociodemographic and clinical data, patient-reported outcome measures relating to self-stigmatization, depression, anxiety, and quality of life were compared across groups. Sociodemographic and clinical factors were tested for their moderating effects between self-stigmatization and quality of life. Group mean comparisons yielded no significant differences in self-stigmatization between patient groups. In both diseases, self-stigmatization significantly predicted depression and anxiety symptoms as well as quality of life. Current symptoms, not having close social relationships, and lower age predicted self-stigma in patients with psoriasis, whereas the involvement of sensitive body areas, the sum of previous treatments, and female sex were predictors in patients with atopic dermatitis. In both groups, symptoms had significantly moderating effects. The results underline the relevance of self-stigmatization in patients with chronic skin diseases. Awareness should be raised, screening implemented, and psychosocial support offered early on. Assessments, conceptual models of self-stigma, and interventions are probably applicable for both diseases
