Antihistamine-resistant chronic spontaneous urticaria: 1-year data from the AWARE study.

BACKGROUND: Previous reports indicate that patients with chronic spontaneous urticaria (CSU) are undertreated and that physicians show poor adherence to guideline recommendations. Awareness of CSU has improved in recent years, but it remains unclear if this has improved the management of these patients in clinical practice. OBJECTIVE: To describe disease burden, quality of life (QoL), and treatment patterns of patients with H1 -antihistamine-refractory CSU in Germany. METHOD: A World-wide Antihistamine-Refractory chronic urticaria (CU) patient Evaluation (AWARE) is a global prospective, non-interventional study of CU in the real-world setting, supported by the manufacturer of omalizumab. Patients (18-75 years) were included who had H1 -antihistamine-refractory CSU for ≥2 months. Disease characteristics, pharmacological treatments, and QoL (dermatology life quality index [DLQI], CU-QoL questionnaire, and angioedema QoL questionnaire) are reported for patients enrolled in Germany. RESULTS: After 1 year in AWARE, CSU remained uncontrolled (urticaria control test [UCT] score <12) in 432 of 1032 (42.2%) patients. QoL impairment remained high after 1 year, with 28.2% of patients reporting that CSU had a moderate/very large/extremely large effect on the DLQI. Most patients did not receive guideline-recommended treatments at the end of the 1-year observation period. Changes in treatments were most evident at the first patient visit, with an increase in patients receiving omalizumab vs prior therapy from 8.5% to 21.4%, and a decrease in those receiving no treatment from 29.9% to 12.8%. These changes were associated with reduced hives, angioedema, UCT scores, and QoL scores at Month 3, but only modest improvements thereafter. Of 528 patients with uncontrolled CSU and who were eligible for treatment escalation, only 3% received up-dosing of H1 -antihistamines and only 5% were initiated on omalizumab during 1 year of treatment. CONCLUSIONS & CLINICAL RELEVANCE: This study highlights a significant discrepancy between recommendations for managing CSU in international guidelines, and in real-world clinical practice in Germany.

Quality of Life in Psoriasis Vulgaris: Use of the ItchyQoL Question-naire in a Secukinumab Phase III Trial in Patients with Psoriasis Vulgaris.

Chronic pruritus is a bothersome symptom in psoriasis vulgaris and can profoundly reduce quality of life (QoL). In this exploratory analysis of the PSORITUS study, the impact of pruritus on QoL in 130 subjects with moderate-to-severe psoriasis was assessed using the ItchyQoL questionnaire. The majority of patients (n = 127) had to scratch their itchy skin regularly, which led to painful skin and frustration (mean ± standard deviation; SD ItchyQoL scores; 4.50 ± 0.56; 3.80 ± 1.09 and 4.20 ± 0.87, respectively). Changes in either temperature or season led to a worsening of itching in most of the patients (n = 126; mean ± SD ItchyQoL score; 3.80 ± 1.02). Many patients felt ashamed (n = 125) or embarrassed (n = 127) due to their itchy skin (mean ± SD ItchyQoL scores; 3.90 ± 1.26 and 3.40 ± 1.19, respectively). The results demonstrated the ItchyQoL questionnaire as a validated tool responsive to treatment for detailed insights into chronic pruritus in patients with psoriasis.

Renal, efficacy and safety outcomes following late conversion of kidney transplant patients from calcineurin inhibitor therapy to everolimus: the randomized APOLLO study.

AIMS: The primary objective of this trial was to demonstrate, based on the estimated glomerular filtration rate (eGFR), superior renal function at month 12 after conversion of maintenance kidney transplant patients from calcineurin inhibitor (CNI) therapy to everolimus, compared to continuing a standard CNI regimen. MATERIALS AND METHODS: APOLLO was an open-label, 12-month, prospective, multicenter study in which 93 maintenance kidney transplant patients were randomized to convert from CNI to everolimus (n = 46) or remain on standard CNI-based immunosuppression (n = 47). The primary efficacy variable was eGFR (Nankivell formula) 12 months after randomization. The study was terminated prematurely due to slow recruitment and was thus underpowered. RESULTS: Mean time post-transplant was 83.5 months with everolimus and 70.1 months with CNI. Adjusted values for eGFR (Nankivell) at month 12 were 61.6 (95% CI 58.1, 65.1) mL/ min/1.73 m² with everolimus and 58.8 (95% CI 55.2, 62.3) mL/min/1.73 m² with CNI, a difference of 2.8 (95% CI -1.0, 6.7) mL/ min/1.73 m² (p = 0.145) i.e., the primary objective was not met. Using the modification of diet in renal disease (MDRD) formula, adjusted eGFR at month 12 was significantly higher with everolimus (p = 0.030). In the subpopulation who remained on the study drug (n = 52), the difference in the adjusted change from randomization was 6.6 (95% CI 1.5, 11.6) mL/min/1.73 m² (p = 0.013) in favor of everolimus. There was no biopsyproven acute rejection and no graft losses. Adverse events led to discontinuation of everolimus and CNI in 32.6% and 10.6% of patients, respectively. CONCLUSIONS: Conversion from CNI to everolimus to preserve renal function can be considered several years after kidney transplantation and does not compromise immunosuppressive efficacy.

Update on the therapy of adult-onset Still's disease with a focus on IL-1-inhibition: a systematic review.

INTRODUCTION: The past decade has seen increasingly rapid advances in understanding the pathogenic nature of adult-onset Still's disease (AOSD) and its shared symptoms with the systemic juvenile idiopathic arthritis (sJIA). Interleukin-1 (IL-1) blocking agents are key elements in the treatment. In this updated systematic review, we focus on studies on efficacy and safety of IL-1 blockers published in the past 5 years and review on latest available therapies. METHODS: We conducted searches using Medline, Biosis, Embase, and Cochrane databases between 2016 and 2021 using the terms AOSD, IL1, IL-18, canakinumab, anakinra, tadekinig, and rilonacept and if applicable their trade names. Duplicates, case reports, and manuscripts with incomplete data were excluded. RESULTS: Of the 1013 screened publications, 17 were eligible after careful selection. We only found two published randomized controlled studies in the past 5 years. Review manuscripts of rare diseases, like our work, usually rely on retrospective studies and case series. Anakinra and canakinumab can be successfully used as first- or further-line treatment in patients with AOSD refractory to steroids. A homogeneous outcome is not established yet. Thus, a combination of clinical and laboratory tests can support the experienced clinician in the decision-making process. CONCLUSION: The approval of IL-1 inhibitors for AOSD brought us into a new era in the treatment of AOSD. The overall efficacy-safety profile of the IL-1 inhibitors is favorable reflecting a targeted approach as standard of care. We can expect that the successful treatment of AOSD with IL-1 inhibition will facilitate further clinical and basic research with impact on other auto-inflammatory and hyper-inflammatory conditions.

People-centered care for psoriasis and urticaria: Are we overlooking Internet addiction while only considering patients and physician settings?

Psoriasis and chronic urticaria (CU) are chronic skin diseases with a high impact on individuals' life and mental health. Some studies indicate a high prevalence of Internet addiction and many affected individuals seem not to utilize healthcare, but rather search for health-related information online. The aims of the study were to assess Internet addiction as a potential comorbidity in both diseases as well as identify differences in healthcare utilization between individuals with psoriasis and CU. This cross-sectional study is based on self-reported data from individuals with psoriasis and CU living throughout Germany using the framework of an online survey from 12/2018 to 01/2019. Advertisements on Google and Facebook were used to address Internet users who searched online for information on psoriasis or CU. The study questionnaire comprised questions on demographics, current contact with physicians, and disease history as well as validated screening tools for well-being and Internet addiction. Overall, 1686 participants (74.0% female, 38.5% psoriasis) with a mean age of 36.9 ± 12.9 years were analyzed. Participants with CU were more likely female (89.2% vs 49.8%, P < 0.001) and not in medical care compared to participants with psoriasis (60.3% vs 45.9%, P < 0.001). Sixteen percent of the participants overall were screened positive for Internet addiction. Furthermore, not utilizing medical care showed a significant association with being screened positive for Internet addiction in participants with CU (adjusted odds ratio [aOR] = 1.49, 95% confidence interval [CI] 1.10-2.02), but not in those with psoriasis. The study revealed a high proportion of affected individuals not being in medical care and a high prevalence of Internet addiction, with individuals with CU not utilizing medical resources having a higher chance of being screened positive for Internet addiction. This underlines the approach of people-centered care and highlights its importance for further research.

Patients with Chronic Urticaria Remain Largely Undertreated: Results from the DERMLINE Online Survey.

INTRODUCTION: Chronic urticaria (CU) is an unpredictable disease, with high disease burden and a significant negative impact on quality of life, especially in patients of working age. Many patients are undertreated, and there is poor awareness of strategies to manage patients with CU in the real-world setting. The current study aimed to gain a better understanding of CU from the patients' perspective, including the body areas most affected by wheals and angioedema, the disease burden and current use of the healthcare system. METHODS: A nationwide online survey was performed in Germany involving individuals who reported a diagnosis of CU and experienced symptoms within 3 months prior to inclusion. RESULTS: This self-report survey included 1037 participants (89.2% female), with a mean ± standard deviation (SD) age of 33.4 ± 11.0 years and a mean ± SD disease duration of 10.0 ± 9.4 years. On average, participants suffered from urticaria symptoms for 3.0 ± 4.3 years before diagnosis. In 73% of participants, symptoms worsened due to external factors, with the majority specifying stress in their personal life or work-related stress as eliciting factors. Within the previous 3 months, 87.4 and 44.1% of participants experienced wheals and angioedema, respectively, at multiple body areas, and most (79.6%) participants had uncontrolled symptoms as measured with the Urticaria Control Test. Despite the high burden of disease, 60.3% of participants stated that they were not currently receiving treatment. The most commonly used therapies to treat CU were oral (72.8%) and non-prescription (43.3%) and prescription (47.3%) topical drugs, with 18.0% of the participants receiving injectable/infused drugs. CONCLUSION: The majority of the participants responding to the survey reported that CU is not sufficiently controlled, thereby severely influencing a highly productive time in their life. The body areas most affected by wheals and angioedema are specified, based on data provided by a large group of affected participants. A greater awareness of disease burden and available treatment options is needed.

Pharmacokinetics and Clinical Outcomes of Generic Tacrolimus (Hexal) Versus Branded Tacrolimus in De Novo Kidney Transplant Patients: A Multicenter, Randomized Trial.

BACKGROUND: Scrupulous comparison of the pharmacokinetic and clinical characteristics of generic tacrolimus formulations versus the reference drug (Prograf) is essential. The pharmacokinetics of the Tacrolimus Hexal (TacHexal) formulation is similar to Prograf in stable renal transplant patients, but data in de novo patients are lacking. METHODS: De novo kidney transplant patients were randomized to generic tacrolimus (TacHexal) or Prograf in a 6-month open-label study. RESULTS: The primary end point, the dose-normalized area under the curve0-12h at month 1 posttransplant, was similar with TacHexal or Prograf; back-transformed geometric means of adjusted log-transformed values (analysis of variance) were 18.99 ng·h·L (TacHexal) and 20.48 ng·h·L (Prograf) (ratio, 1.08; 90% confidence interval, 0.84-1.38; P = 0.605). The dose-normalized peak concentration geometric means at month 1 was also comparable between treatments (ratio, 1.16; 90% confidence interval, 0.88-1.54; P = 0.377). There were no relevant differences in other pharmacokinetic parameters at month 1 or in area under the curve0-4h and trough concentration when measured at months 3 and 6. The adjusted change in mean estimated glomerular filtration rate from baseline to month 6 (Nankivell) was noninferior for TacHexal versus Prograf using observed values (47.7 vs 38.6 mL/min per 1.73 m, P < 0.001) and was superior based on observed values (P = 0.044) but not using last observation-carried forward method. Rates of biopsy-proven acute rejection (5.7% vs 7.9%), adverse events, and serious adverse events were similar with TacHexal or Prograf. CONCLUSION: Tacrolimus pharmacokinetics is similar with TacHexal and Prograf early after kidney transplantation. Efficacy and safety in this limited data set were comparable, with at least equivalent graft function under TacHexal.

Renal function to 5 years after late conversion of kidney transplant patients to everolimus: a randomized trial.

BACKGROUND: Few trials have investigated late preemptive conversion of kidney transplant patients from a calcineurin inhibitor (CNI) to an mTOR inhibitor. METHODS: In an open-label, 12-month, prospective, randomized, parallel-group study, maintenance kidney transplant patients (>6 months post-transplant) either switched from CNI to everolimus or continued their current CNI regimen. Patients who completed the core study were followed to 5 years post-randomization. RESULTS: Of 93 randomized patients, 78 completed the core study and 67 attended the final 60-month study visit. Mean time post-transplant at baseline was 82.6 months and 70.5 months in the everolimus and CNI groups, respectively. At month 60, adjusted mean eGFR (Nankivell) was 63.0 (95% CI 57.8, 68.2) mL/min/1.73 m(2) in the everolimus group versus 57.9 (95% CI 52.6, 63.1) mL/min/1.73 m(2) in the CNI group, a difference of 5.1 (95% CI -0.6, 10.8) mL/min/1.73 m(2) (p = 0.076). Among patients who remained on randomized study drug at month 60, mean eGFR (Nankivell) was 71.6 (95% CI 64.2, 79.0) mL/min/1.73 m(2) in everolimus-treated patients (n = 21) versus 60.6 (95% CI 55.1, 66.1) mL/min/1.73 m(2) in CNI-treated patients (n = 29) (mean difference 11.0; 95% CI 3.6, 18.5 mL/min/1.73 m(2); p = 0.005). No cases of BPAR occurred from randomization to month 60 in either group. Graft loss occurred in three everolimus-treated patients and one CNI-treated patient. No unexpected safety concerns were observed in either group. CONCLUSION: Late preemptive conversion of maintenance kidney transplant patients from CNI to everolimus may be associated with improved long-term renal function and preserves immunosuppressive efficacy. Patient numbers were low, but these findings merit further investigation.