Secukinumab demonstrated sustained retention, effectiveness and safety in a real-world setting in patients with moderate-to-severe plaque psoriasis: long-term results from an interim analysis of the SERENA study.

BACKGROUND: Randomized controlled trials of secukinumab have shown sustained efficacy and a favourable safety profile in multiple manifestations of psoriatic disease. OBJECTIVES: To assess the long-term, real-world retention, effectiveness and safety of secukinumab in routine clinical practice for the treatment of moderate-to-severe plaque-type psoriasis (PsO). METHODS: SERENA (CAIN457A3403) is a large, ongoing, longitudinal, observational study conducted at 438 sites and 19 countries for an expected duration of up to 5 years in adult patients with moderate-to-severe PsO, psoriatic arthritis and ankylosing spondylitis. Patients received ≥16 weeks of secukinumab treatment before enrolment. This interim analysis presents data from PsO patients, who were enrolled in the study between October-2016 and October-2018 and were observed for ≥2 years. RESULTS: In total, 1756 patients (67.3% male) with a mean age of 48.4 years and body mass index of 28.8 kg/m2 were included in the analysis. The secukinumab treatment retention rates after 1, 2 and 3 years in the study were 88.0%, 76.4% and 60.5%, respectively. Of the 648 patients who discontinued the study, the most common reasons included lack of efficacy (42.6%), adverse event (17.4%), physician decision (12.2%) and subject decision (11.6%). Mean ± SD absolute PASI was 21.0 ± 13.0 at the start of treatment (n = 1,564). At baseline, the mean ± SD PASI score reduced to 2.6 ± 4.8 and remained low at Year 1 (2.3 ± 4.3), Year 2 (1.9 ± 3.6) and Year 3 (1.9 ± 3.5). The safety profile of secukinumab during the SERENA study was consistent with its known safety profile, with no new safety signals reported. Particularly, low rates of inflammatory bowel disease (0.3%; Incidence Rate [IR]:0.15), candida infections (3.1%; IR:1.43) and MACE (0.9%; IR:0.37) were observed. CONCLUSIONS: Secukinumab showed high treatment persistence, sustained effectiveness and a favourable safety profile up to 3 years of follow-up in the real-world population of PsO patients observed in SERENA.

Biologic drug survival rates in the era of anti-interleukin-17 antibodies: a time-period-adjusted registry analysis.

BACKGROUND: Drug survival rates reflect efficacy and safety and may be influenced by the availability of alternative treatment options. Little is known about time-dependent drug survival in psoriasis and the effect of increasing numbers of biologic treatment options. OBJECTIVES: To determine whether drug survival is influenced by the availability of treatment options and by factors such as gender, psoriatic arthritis or previous biologic treatment. METHODS: This observational, retrospective, multicentre cohort study analysed data from patients registered in the Austrian Psoriasis Registry (PsoRA) who were treated with biologics between 1 January 2015 and 30 November 2019. RESULTS: A total of 1572 patients who received 1848 treatment cycles were included in this analysis. The highest long-term Psoriasis Area and Severity Index improvement was observed after treatment with ixekizumab, followed by ustekinumab and secukinumab, adalimumab and etanercept. Overall, ustekinumab surpassed all other biologics in drug survival up to 48 months. However, when adjusted for biologic naïvety, its superiority vanished and drug survival rates were similar for ixekizumab (91·6%), secukinumab (90·2%) and ustekinumab (92·8%), all of them superior to adalimumab (76·5%) and etanercept (71·9%) at 12 months and beyond. Besides biologic non-naïvety (2·10, P < 0·001), the introduction of a new drug such as secukinumab or ixekizumab (relative hazard ratio 1·6, P = 0·001) and female gender (1·50, P = 0·019) increased the risk of treatment discontinuation overall, whereas psoriatic arthritis did not (1·12, P = 0·21). CONCLUSIONS: The time-dependent availability of drugs should be considered when analysing and comparing drug survival. Previous biologic exposure significantly influences drug survival. Women are more likely to stop treatment.

Characteristics and outcomes of patients treated with apremilast in the real world: results from the APPRECIATE study.

BACKGROUND: APPRECIATE is a multinational, observational, retrospective, cross-sectional study in patients treated for psoriasis with apremilast, an oral phosphodiesterase 4 inhibitor. OBJECTIVES: To describe the characteristics of patients with psoriasis treated with apremilast in the clinical setting, to evaluate real-world outcomes of psoriasis treatment with apremilast and to better understand the perspectives of patients and physicians on treatment outcomes. METHODS: In six European countries, patients with chronic plaque psoriasis treated in clinical practice who could be contacted 6 (±1) months after apremilast initiation were enrolled. Patient characteristics, Dermatology Life Quality Index (DLQI) and Psoriasis Area and Severity Index (PASI) were obtained from medical records when available. Outcomes were evaluated using patient/physician questionnaires. RESULTS: In 480 patients at treatment initiation, mean [median; 95% confidence interval (CI)] PASI and DLQI scores were 12.5 (10.7; 11.6-13.4) and 13.4 (13.0; 11.4-14.2), respectively. At 6 (±1) months, 72.3% of patients (n = 347) continued apremilast treatment [discontinuations: lack of efficacy (13.5%), safety (11.7%), other (2.5%)]. In patients continuing treatment, 48.6% achieved a ≥75% reduction in PASI score; mean (95% CI) DLQI score was 5.7 (4.5-6.9), and mean (SD) Patient Benefit Index score was 2.8 (1.2). Physicians perceived clinical improvement in 75.6% of patients. Physicians' perspective on overall success of apremilast in meeting expectations correlated with patients' perception of treatment benefit (r = 0.691). Most commonly reported adverse events (>5% of patients) were diarrhoea, nausea and headache. CONCLUSIONS: Patients in APPRECIATE reported high disease burden despite more moderate skin involvement than those who enrolled in clinical trials of apremilast. Findings from APPRECIATE demonstrate the real-world value of apremilast for psoriasis treatment, as 7 of 10 patients continued therapy and showed notable improvement in disease severity and quality of life 6 (±1) months after apremilast initiation.

EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris - Part 2: specific clinical and comorbid situations.

This evidence- and consensus-based guideline on the treatment of psoriasis vulgaris was developed following the EuroGuiDerm Guideline and Consensus Statement Development Manual. The second part of the guideline provides guidance for specific clinical and comorbid situations such as treating psoriasis vulgaris patient with concomitant psoriatic arthritis, concomitant inflammatory bowel disease, a history of malignancies or a history of depression or suicidal ideation. It further holds recommendations for concomitant diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or patients with a wish for a child in the near future. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.

EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris - Part 1: treatment and monitoring recommendations.

This evidence- and consensus-based guideline on the treatment of psoriasis vulgaris was developed following the EuroGuiDerm Guideline and Consensus Statement Development Manual. The first part of the guideline includes general information on the scope and purpose, health questions covered, target users and strength/limitations of the guideline. Suggestions for disease severity grading and treatment goals are provided. It presents the general treatment recommendations as well as detailed management and monitoring recommendations for the individual drugs. The treatment options discussed in this guideline are as follows: acitretin, ciclosporin, fumarates, methotrexate, adalimumab, apremilast, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab.

ALIGNed on adherence: subanalysis of adherence in immune-mediated inflammatory diseases in the DACH region of the global ALIGN study.

BACKGROUND: Non-adherence to medication is a challenging problem in daily clinical practice. OBJECTIVE: To assess reasons for non-adherence in patients with chronic immune-mediated inflammatory diseases (IMIDs) in a direct comparison including evaluation of treatment necessity and concerns. METHODS: ALIGN was a non-interventional, multicountry, multicentre, self-administered, cross-sectional, epidemiologic survey study. Here, we investigate the German, Austrian and Swiss (DACH) cohort. Six hundred thirty-one patients with different IMIDs (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn's disease and ulcerative colitis) under systemic therapies were evaluated concerning adherence, beliefs of necessity and concerns towards treatment in patients with IMIDs. RESULTS: The DACH cohort had significantly different levels of adherence depending on the IMID (P < 0.05) and the type of therapy (P < 0.05). Based on the significant influence of concerns on treatment adherence (P < 0.05) and the high belief of treatment necessity, patients could be classified in four attitudinal segments, which were unequally distributed throughout various IMIDs. High concerns had a significant influence on non-adherence, whereas necessity did not. Older age, female sex, TNFi mono-, conventional combination and TNFi combination therapy are positively associated with adherence. CONCLUSIONS: In the DACH region, patients are less concerned about medication and believe in the necessity of treatment. Therefore, we suggest adapting the communication in the various patient groups.

[Anaphylactic reaction to camomile tea]. / Anaphylaxie auf Kamillentee.

The case of a man with type I allergy after the intake of camomile tea is presented. About 30 min after consumption he was hospitalised with palmar pruritus, swelling of the eyelids, upper lip and nasal mucosa as well as narrowness of the throat. Hereditary angioedema was excluded. The skin prick test confirmed the diagnosis of a type I allergy due to camomile tea.

[Intradermal metal deposits in an industrial worker]. / Intradermale Metalleinsprengungen bei einem Industriearbeiter.

CASE REPORT: We describe a 75-year-old patient with asymptomatic grey pigmentation on the face and fingers. He had worked over two decades in cutting high-voltage cables. The cutting procedures were performed without a face shield or protection gloves. The patient presented with gray punctate lesions beside some homogeneously stained zones. DIAGNOSTICS: Histologically, the deposits presented in the dermal tissue in a horse-shoe, oval, or splinter-like shape. The foreign body material was embedded by a few CD68-positive macrophages. Undyed histological sections were investigated via two-dimensional micro-synchrotron X-ray fluorescence analysis (SRXRF). The deposits were identified as zinc (Zn), copper (Cu), nickel (Ni), and strontium (Sr), which were strongly associated with maximal sulfur (S) concentrations. This association is presumably induced by complex binding between thiol groups and metal ions such as Zn, Ni etc. However, the iron (Fe) distribution patterns were quite different to those of Zn, Cu, or Ni. These heavy metals are major components of the metal wires that the patient worked with in his profession. CONCLUSION: To the best of our knowledge, this is the first case report in the dermatological literature of intradermal metal deposits identified via SRXRF analysis.

Adalimumab in the treatment of moderate-to-severe chronic plaque psoriasis in patients switching from other biologics.

BACKGROUND: Ample evidence shows that switching from one biological agent to another may prove effective when response to the first one is inadequate. Nevertheless, there are little data so far showing the efficacy and safety of adalimumab in patients with plaque psoriasis who previously received another biologic agent. OBJECTIVE: We evaluated the 1-year effectiveness, safety and quality-of-life outcomes patients with psoriasis who had switched to adalimumab from other biologic therapies. METHODS: Forty-two patients who participated in this Austrian multicenter study were treated with adalimumab over a 1-year period, after switching from efalizumab, infliximab or etanercept. Effectiveness was assessed using standardized tools for measurement of disease severity [Psoriasis Area and Severity Index (PASI) and Nail Psoriasis Severity Index (NAPSI)] and quality of life [Dermatology Life Quality Index (DLQI)]. The study endpoints were evaluated using the all-treated population. RESULTS: The mean percentage of improvement at the end of the study was 74.3% for PASI, 81.6% for DLQI and 83.6% for NAPSI, demonstrating a considerable benefit of treatment with adalimumab. The safety profile observed was consistent with previous clinical trials for adalimumab, and no new safety signals were observed. CONCLUSION: Adalimumab therapy in patients with plaque psoriasis previously treated with other biologic agents demonstrates effectiveness, safety and improvement in quality of life.

Real-world effectiveness of anti-interleukin-23 antibodies in chronic plaque-type psoriasis of patients from the Austrian Psoriasis Registry (PsoRA).

With the introduction of the latest class of biologic drugs targeting interleukin (IL)-23p19, three new, highly effective drugs can be used for the treatment of chronic plaque psoriasis. However, poorer skin improvement as well as higher rates of serious adverse events have been reported for patients under real-world conditions (outside clinical trials). This accounts especially for patients who have already been treated with biologic drugs. We therefore aimed to determine effectiveness and safety of IL-23p19 inhibitors in real-world patients by analysing data from the Psoriasis Registry Austria (PsoRA) in this observational, retrospective, multicentre cohort study. Data for 197 patients (52.3% biologic-non-naïve), who were treated with anti-IL-23p19 antibodies (127 guselkumab, 55 risankizumab and 15 tildrakizumab) for at least 3 months, were eligible for analysis. In general, biologic-non-naïve patients displayed a less favourable response to anti-IL-23 treatment as compared to biologic-naïve patients. However, after correction for previous biologic exposure, few differences in PASI improvement were detected among biologic-naïve and -non-naïve patients treated with different IL-23p19 inhibitors. This indicates that treatment effectiveness is not related to the class of the previously administered therapy in biologic-non-naïve patients. Therefore, IL-23p19 inhibitors represent a promising treatment alternative for patients who have not responded to previous biologics. However, as with other biologic agents (including IL-17 inhibitors), we did not observe an entirely satisfactory treatment response (i.e. PASI < 3 and/or PASI 75) to anti-IL-23 treatment in one out of four to five patients. Adverse events (mainly non-severe infections) were observed in 23 (11.7%) patients with no major differences regarding the administered IL-23 inhibitor or previous biologic exposure.

Response of vitiligo to once- vs. twice-daily topical tacrolimus: a controlled prospective, randomized, observer-blinded trial.

BACKGROUND: A few studies on the treatment of vitiligo with topical tacrolimus have been published and showed promising results. However, most of these trials were uncontrolled. OBJECTIVE: This study aims to assess the response of vitiligo to once- or twice-daily treatment with 0.1% tacrolimus in a controlled, randomized, observer-blinded study. METHODS: Seventeen patients with generalized vitiligo were enrolled in this study. In each patient, two lesions were selected and randomized to treatment with either once- or twice-daily application of 0.1% tacrolimus for a total period of 6 months. In 10 patients, a third patch was left untreated to serve as a control. RESULTS: Fifteen patients with 40 target lesions completed the study. Twice-daily treatment induced excellent (> 75%) repigmentation in two lesions, moderate (> 25-50%) and poor (1-25%) repigmentation in four lesions each, and no response in five lesions. Once-daily treatment resulted in moderate repigmentation in two lesions and poor repigmentation in five lesions, whereas no effect was observed in the remaining eight lesions. One out of 10 control lesions developed moderate spontaneous repigmentation, the other nine remained unchanged. Besides the frequency of tacrolimus application, the treatment outcome was determined by the localization of the affected areas with the facial region showing the best response. CONCLUSIONS: Tacrolimus ointment appears to be an effective treatment option for facial vitiligo. A guarded prognosis is advisable for vitiliginous lesions on other localizations. Treatment must be applied twice daily for optimum response.

Clinical profile of a new hormone replacement therapy containing 2 mg 17 beta-estradiol and 10 mg dydrogesterone.

OBJECTIVE: Patient's acceptability, compliance, and effectiveness of a new sequential hormone replacement regimen containing 2 mg 17beta-estradiol and 10 mg dydrogesterone, were assessed in a 3-month, open, multicentre study involving 110 menopausal women. METHODS: A specially designed menopause score was used to assess the severity of menopausal symptoms, each symptom being graded at baseline and after 3 months on a four-point scale. Bleeding data were recorded by the patient on a diary card. Serum hormone levels including FSH, LH, E2, P, PRL, DHEA-S, T, SHBG were checked at the initial visit and at the end of the study. RESULTS: After 3 months of treatment, all but four of the 34 climacteric symptoms investigated showed a significant improvement. There were no significant changes noted in body weight. The average duration and flow of bleeding showed no significant changes during hormone replacement therapy (HRT). There were no serious adverse events related to treatment. CONCLUSION: The 17beta-estradiol/dydrogesterone combination HRT reduced effectively climacteric symptoms, showed no significant changes in endometrial thickness as determined by transvaginal ultrasonography and provided excellent cycle control.

The influence of hormone replacement therapy on skin ageing: a pilot study.

OBJECTIVES: We studied the effect of hormonal treatment on skin ageing in menopausal women. METHODS: Twenty-four patients (45-68 years; mean age, 54.9 years) without hormone treatment for at least 6 months were included. Patients were assigned to three therapy groups: 1, oestrogen only (Estraderm TTS 50) (n=6); 2, transdermal oestrogen and progesterone (Estraderm TTS 50 and 0.4 mg progesterone vaginal suppository) (n=7); and 3, oral oestrogen and progesterone (2 mg Progynova and 0.4 mg progesterone vaginal suppository) (n=8). One group without therapy was included as a control group (n=3). Treatment was continued for 6 months. Three patients, one from group 2 and two from group 3, discontinued therapy before the study endpoint. The following skin parameters were measured at monthly intervals during treatment: skin surface lipids, epidermal skin hydration, skin elasticity and skin thickness. Concomitant clinical evaluation included a subjective clinical evaluation form, a patient questionnaire and laboratory tests for oestradiol, progesterone and follicle stimulating hormone. RESULTS: Mean levels of epidermal skin moisture, elasticity and skin thickness were improved at the end of treatment based on both subjective and objective evaluation in patients with hormone replacement therapy (HRT). Skin surface lipids were increased during combined HRT, which may reflect stimulatory effects of the progestagen component on sebaceous gland activity, while oestrogen alone has a sebum-suppressive action. In the HRT groups, the questionnaire for climacteric complaints demonstrated significant improvements, while laboratory tests showed increases in oestradiol and progesterone and decreases in FSH. CONCLUSIONS: HRT with the mentioned regimes significantly improved parameters of skin ageing.

[Leucocytoclastic eosinophilic vasculitis with Löffler syndrome]. / Leukozytoklastische eosinophile Vaskulitis bei eosinophilem Lungeninfiltrat "Löffler"

Histologically, leukocytoclastic vasculitis (LV) presents with neutrophilic granulocytes with leukocytoclasia and erythrocyte extravasation, associated with variable counts of lymphocytes, plasma cells and eosinophilic granulocytes. The association of a LV with eosinophilic granulocytes and eosinophilic pneumonia was first described by Chan et al. in 1982. Our case represents the second report in the literature of this rare disease: a 85 year old patient with LV and numerous eosinophilic granulocytes in association with intermittent blood eosinophilia and Löffler syndrome (eosinophilic pulmonary infiltrates). The recurrent episodes were treated successfully with oral corticosteroids.

A prospective, randomized, double-blind, placebo-controlled study on the influence of a hormone replacement therapy on skin aging in postmenopausal women.

BACKGROUND: There is mounting evidence that menopause affects some functions of the skin. Hormone replacement therapy (HRT) appears to limit some of the climacteric aspects of cutaneous aging. OBJECTIVE: In the light of a growing interest in the endocrinological influence of skin, we performed a study evaluating the effects of HRT on skin aging in postmenopausal women. METHODS: Forty non-hysterectomized, postmenopausal women were included in this prospective, randomized, double-blind, placebo-controlled study on the influence of oral sequential treatment with a combination of 2 mg 17beta-estradiol/10 mg dydrogesterone (Femoston) for seven 28-day cycles. Skin elasticity, skin surface lipids, skin hydration and skin thickness were measured by non-invasive methods, and both adverse-event profile and clinical-dermatological status were evaluated. RESULTS: After 7 months of HRT, skin elasticity increased significantly at the right ramus of the mandible, while skin hydration tended to improve significantly at the right upper arm (inner side); skin thickness improved significantly but skin surface lipids did not. Absolute effects did not differ significantly between HRT and placebo patients. A dermatological evaluation was largely consistent with measurement results. Safety and tolerability of HRT were positive. CONCLUSION: The results showed improvements in the parameters involved in skin aging in the HRT group as compared to baseline. While skin aging is no indication for systemic hormone supplementation, a positive effect on aging skin can be observed.

Clinical evidence of the endocrinological influence of a triphasic oral contraceptive containing norgestimate and ethinyl estradiol in treating women with acne vulgaris. A pilot study.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the efficacy of a triphasic combination oral contraceptive (OC) containing norgestimate and ethinyl estradiol in the treatment of women with acne vulgaris. METHODS: 12 female patients were included and 10 completed the trial. Over a period of 6 months, efficacy was assessed by means of facial acne lesion counts, by an investigator's global assessment, by patients' self-assessments and by measuring epidermal moisture and skin surface lipids. In addition, a photo documentation was compiled and hormone levels were measured. RESULTS: After 6 months of therapy, the number of acne counts improved. The success of treatment was rated positively both by the investigator and by all patients but one who did not report any changes. Skin surface lipids were significantly reduced while skin hydration showed no significant change. Testosterone and progesterone decreased, and sex-hormone-binding globulin increased, significantly. CONCLUSION: Our data show that an OC containing norgestimate and ethinyl estradiol is a good therapeutic option for women of fertile age suffering from mild to moderate acne vulgaris.