Hidradenitis suppurativa affects approximately 1% of the population.
Highlighting the relevance of self-management-competency as a new therapeutic target.
258 patients from the 'Epidemiology and Care ...in Acne inversa (EpiCAi)' project were included in the study. Disease burden was measured by patient-rated questionnaires in terms of disease activity, pain, quality of life, depression and insomnia and correlated with the domains of the health education impact questionnaire (heiQ) measuring self-management-competency.
66 male (25.6%) and 192 female (74.4%) patients, with a mean age of 40.3 ± 10.24 years were included. Mean scores of pain on the numeric rating scale (NRS), Dermatology Life Quality Index (DLQI) and Hospital Anxiety and Depression Scale (HADS) were 5.11 ± 2.68, 11.35 ± 7.79 and 13.71 ± 7.57, respectively. The Insomnia severity index (ISI) showed a mean of 9.58 ± 5.76. The HADS has the highest increased total risk across all heiQ domains. With respect to the heiQ domains, the highest exposure can be attributed to improving constructive attitudes and approaches as well as decreasing emotional distress.
There is a clear association of self-management-competency with overall disease burden, which underlines the need for psychoeducational support. This study provides ideas to develop new possible strategies of care.
Background
An objective of the phase 3 HELP Study was to investigate the effect of lanadelumab on health‐related quality of life (HRQoL) in patients with hereditary angioedema (HAE).
Methods
Patients ...with HAE‐1/2 received either lanadelumab 150 mg every 4 weeks (q4wks; n = 28), 300 mg q4wks (n = 29), 300 mg every 2 weeks (q2wks; n = 27), or placebo (n = 41) for 26 weeks (days 0–182). The Angioedema Quality of Life Questionnaire (AE‐QoL) was administered monthly, consisting of four domain (functioning, fatigue/mood, fears/shame, nutrition) and total scores. The generic EQ‐5D‐5L questionnaire was administered on days 0, 98, and 182. Comparisons were made between placebo and (a) all lanadelumab‐treated patients and (b) individual lanadelumab groups for changes in scores (day 0–182) and proportions achieving the minimal clinically important difference (MCID, −6) in AE‐QoL total score.
Results
Compared with the placebo group, the lanadelumab total group demonstrated significantly greater improvements in AE‐QoL total and domain scores (mean change, −13.0 to −29.3; p < 0.05 for all); the largest improvement was in functioning. A significantly greater proportion of the lanadelumab total group achieved the MCID (70% vs 37%; p = 0.001). The lanadelumab 300 mg q2wks group had the highest proportion (81%; p = 0.001) and was 7.2 times more likely to achieve the MCID than the placebo group. Mean EQ‐5D‐5L scores at day 0 were high in all groups, indicating low impairment, with no significant changes at day 182.
Conclusion
Patients with HAE‐1/2 experienced significant and clinically meaningful improvements in HRQoL measured by AE‐QoL following lanadelumab treatment in the HELP Study.
In the phase 3 HELP Study, HRQoL (health‐related quality of life) of patients with HAE (hereditary angioedema)‐1/2 was evaluated using the angioedema‐specific AE‐QoL (Angioedema Quality of Life Questionnaire). After 26 weeks, lanadelumab‐treated patients experienced significantly greater HRQoL improvements than placebo‐treated patients. Patients receiving lanadelumab 300 mg q2wks (every 2 weeks) were most likely to see clinically meaningful benefit, with 81% reaching the MCID (minimal clinically important difference) and seven times greater odds vs placebo for this achievement.
Abbreviations: AE‐QoL, Angioedema Quality of Life Questionnaire; HAE, hereditary angioedema; HRQoL, health‐related quality of life; MCID, minimal clinically important difference; q2wks, every 2 weeks; q4wks, every 4 weeks.
Summary
Background
Basal cell carcinoma (BCC) represents the most common nonmelanoma skin cancer worldwide, affecting mainly adult, fair‐skinned individuals. The World Health Organization ...distinguishes aggressive and nonaggressive forms, of which prototypical variants of the latter are primary nodular and superficial BCC.
Objectives
To demonstrate noninferiority of BF‐200 ALA (a nanoemulsion gel containing 5‐aminolaevulinic acid) compared with MAL (a cream containing methyl aminolaevulinate) in the treatment of nonaggressive BCC with photodynamic therapy (PDT). Noninferiority of the primary efficacy variable (overall patient complete response 12 weeks after last PDT) would be declared if the mean response for BF‐200 ALA was no worse than that for MAL, within a statistical margin of Δ = −15%.
Methods
The study was a randomized, phase III trial performed in Germany and the U.K. with ongoing 5‐year follow‐up. Of 281 randomized patients, 138 were treated with BF‐200 ALA and 143 with MAL. Patients received two PDT sessions 1 week apart. Remaining lesions 12 weeks after the second PDT were retreated. Illumination was performed with a red light source (635 nm, 37 J cm−2). The results shown include clinical end points and patients’ reassessment 12 months after the last PDT. The study was registered with EudraCT (number 2013‐003241‐42).
Results
Of the BF‐200 ALA‐treated patients, 93·4% were complete responders compared with 91·8% in the MAL group. The difference of means was 1·6, with a one‐sided 97·5% confidence interval of −6·5, establishing noninferiority (P < 0·0001). The results for secondary efficacy parameters were in line with the primary outcome. Recurrence rates 12 months after the last treatment were ≤ 10%.
Conclusions
Treatment of nonaggressive BCC with BF‐200 ALA‐PDT is highly effective and well tolerated with proven noninferiority to MAL‐PDT. It demonstrates low recurrence rates after 1 year of follow‐up.
What's already known about this topic?
Photodynamic therapy (PDT) using BF‐200 aminolaevulinic acid (ALA) gel is registered and highly effective in the treatment of mild‐to‐moderate actinic keratosis and field cancerization.
BF‐200 ALA gel was recently approved for the treatment of superficial and/or nodular basal cell carcinoma (BCC) unsuitable for surgical treatment.
PDT using methyl aminolaevulinate (MAL) cream is approved for the treatment of thin or nonhyperkeratotic and nonpigmented actinic keratoses, Bowen disease, and superficial and nodular BCCs when other therapies are considered less appropriate.
What does this study add?
BF‐200 ALA‐PDT is confirmed to be significantly noninferior to MAL‐PDT for the treatment of nonaggressive BCC.
Treatment‐emergent adverse events were comparable between the two patient groups, with similar or slightly lower recurrence rates for BF‐200 ALA gel compared with MAL cream after 12 months.
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Hereditary angioedema due to C1 inhibitor (C1 esterase inhibitor) deficiency (types I and II HAE-C1-INH) is a rare disease that usually presents during childhood or adolescence with intermittent ...episodes of potentially life-threatening angioedema. Diagnosis as early as possible is important to avoid ineffective therapies and to properly treat swelling attacks. At a consensus meeting in June 2011, pediatricians and dermatologists from Germany, Austria, and Switzerland reviewed the currently available literature, including published international consensus recommendations for HAE therapy across all age groups. Published recommendations cannot be unconditionally adopted for pediatric patients in German-speaking countries given the current approval status of HAE drugs. This article provides an overview and discusses drugs available for HAE therapy, their approval status, and study results obtained in adult and pediatric patients. Recommendations for developing appropriate treatment strategies in the management of HAE in pediatric patients in German-speaking countries are provided.
Conclusion
Currently, plasma-derived C1 inhibitor concentrate is considered the best available option for the treatment of acute HAE-C1-INH attacks in pediatric patients in German-speaking countries, as well as for short-term and long-term prophylaxis.
Background
Hereditary angioedema (HAE) due to C1 inhibitor deficiency manifests as recurrent swelling attacks that can be disabling and sometimes fatal. Long‐term prophylaxis with twice‐weekly ...intravenous injections of plasma‐derived C1‐inhibitor (pdC1‐INH) has been established as an effective treatment. Subcutaneous (SC) administration of pdC1‐INH has not been studied in patients with HAE.
Methods
This open‐label, dose‐ranging, crossover study (COMPACT Phase II) was conducted in 18 patients with type I or II HAE who received two of twice‐weekly 1500, 3000, or 6000 IU SC doses of highly concentrated volume‐reduced CSL830 for 4 weeks each. The mean trough plasma levels of C1‐INH functional activity, C1‐INH and C4 antigen levels during Week 4, and overall safety and tolerability were evaluated. The primary outcome was model‐derived steady‐state trough C1‐INH functional activity.
Results
After SC CSL830 administration, a dose‐dependent increase in trough functional C1‐INH activity was observed. C1‐INH and C4 levels both increased. The two highest dose groups (3000 and 6000 IU) achieved constant C1‐INH activity levels above 40% values, a threshold that was assumed to provide clinical protection against angioedema attacks. Compared with intravenous injection, pdC1‐INH SC injection with CSL830 showed a lower peak‐to‐trough ratio and more consistent exposures. All doses were well tolerated. Mild‐to‐moderate local site reactions were noted with pain and swelling being the most common adverse event.
Conclusions
Subcutaneous volume‐reduced CSL830 was well tolerated and led to a dose‐dependent increase in physiologically relevant functional C1‐INH plasma levels. A clinical outcome study of SC CSL830 in patients with HAE warrants further investigation.
Background
Lanadelumab demonstrated efficacy in preventing hereditary angioedema (HAE) attacks in the phase 3 HELP Study.
Objective
To assess time to onset of effect and long‐term efficacy of ...lanadelumab, based on exploratory findings from the HELP Study.
Methods
Eligible patients with HAE type I/II received lanadelumab 150 mg every 4 weeks (q4wks), 300 mg q4wks, 300 mg q2wks, or placebo. Ad hoc analyses evaluated day 0‐69 findings using a Poisson regression model accounting for overdispersion. Least‐squares mean monthly HAE attack rate for lanadelumab was compared with placebo. Intrapatient comparisons for days 0‐69 versus steady state (days 70‐182) used a paired t test for continuous endpoints or Kappa statistics for categorical endpoints.
Results
One hundred twenty‐five patients were randomized and treated. During days 0‐69, mean monthly attack rate was significantly lower with lanadelumab (0.41‐0.76) vs placebo (2.04), including attacks requiring acute treatment (0.33‐0.61 vs 1.66) and moderate/severe attacks (0.31‐0.48 vs 1.33, all P ≤ .001). More patients receiving lanadelumab vs placebo were attack free (37.9%‐48.1% vs 7.3%) and responders (85.7%‐100% vs 26.8%). During steady state, the efficacy of lanadelumab vs placebo was similar or improved vs days 0‐69. Intrapatient differences were significant with lanadelumab 300 mg q4wks for select outcomes. Lanadelumab efficacy was durable—HAE attack rate was consistently lower vs placebo, from the first 2 weeks of treatment through study end. Treatment emergent adverse events were comparable during days 0‐69 and 70‐182.
Conclusion
Protection with lanadelumab started from the first dose and continued throughout the entire study period.
During days 0‐69, lanadelumab‐treated patients had a significantly lower mean monthly hereditary angioedema (HAE) attack rate vs placebo and were more likely to be responders and attack free. Protection starts early and is sustained; during steady state, lanadelumab efficacy was similar or improved vs days 0‐69. Prophylactic agents with rapid onset, sustained effect, and convenient dosing frequency can improve HAE management plans. Abbreviations: HAE, hereditary angioedema; q2wks, every 2 weeks.
Background
Mastocytosis is a heterogeneous disease characterized by a clonal expansion of mast cells in various organs. The vast majority of patients affected suffer from signs and symptoms caused by ...mediator release from mast cells. Although the disease burden is high, there is currently no specific instrument to measure health‐related quality of life (HRQoL) impairment in patients with mastocytosis.
Objective
The aim of this study was to develop and validate a disease‐specific tool to assess HRQoL impairment in patients with cutaneous and indolent systemic mastocytosis, the Mastocytosis Quality of Life Questionnaire (MC‐QoL).
Methods
Sixty‐two potential MC‐QoL items were developed in a combined approach consisting of semi‐structured patient interviews, expert input and literature research. Item selection was performed by impact analysis with 76 patients and a final review for face validity. The resulting MC‐QoL was tested for validity, reliability and influence factors. In parallel, an US American‐English version of the MC‐QoL was developed.
Results
A total of 158 patients (41 CM, 41 MIS and 76 ISM) took part in the MC‐QoL validation study. The final 27‐item questionnaire was found to have a four‐domain structure (‘symptoms’, ‘emotions’, ‘social life/functioning’ and ‘skin’), a valid total score and an excellent test–retest reliability. Multiple regression analysis revealed disease duration, but not age, gender or skin involvement to be a significant determinant of HRQoL impairment in mastocytosis.
Conclusions
The MC‐QoL is the first disease‐specific HRQoL questionnaire for adult patients with cutaneous and indolent systemic mastocytosis. This short, validated and reliable instrument will serve as a valuable tool in future clinical studies and in routine patient care.
Background: Skin swellings are the most frequent symptoms in hereditary angio‐oedema (HAE) arising out of C1‐inhibitor (C1‐INH) deficiency. They may be painful and impact daily activities of ...patients. Detailed clinical data concerning the treatment of skin swellings by C1‐INH concentrate have not been reported yet.
Methods: From 1976 through 2007, a total of 2104 skin‐swelling attacks in 47 patients with HAE were treated with the C1‐INH concentrate. Time to relief and duration of the swellings were documented during personal interviews using standardized questionnaires. The results were compared with 9046 untreated skin swellings in the same patients.
Results: The first clinical sign of efficacy was a slowdown of progress of symptoms accompanied by a decreased feeling of tension and pain in the swollen area. The mean time to the first relief of symptoms was 1.1 ± 1.4 h in treated skin swellings and 50.4 ± 33 h in untreated skin swellings. Improvement of facial skin swellings took longer than swellings of the extremities, genitals or trunk. The duration of treated skin swellings was 1.7 day in treated and 3.2 day in untreated ones. In treated swellings, there was long‐lasting control and no rebound within the 48 h following the drug administration and no laryngeal oedema following facial oedema were observed. No severe side‐effects occurred.
Conclusions: The C1‐INH concentrate has proven to be highly effective and safe for treating skin swellings in patients with HAE arising out of C1‐INH deficiency.
Summary
Background Chronic urticaria (CU), one of the most common skin disorders, is characterized by spontaneous recurrent bouts of weals and pruritus and associated with severely impaired quality ...of life (QoL).
Objectives To determine what aspects of life quality are affected and to characterize the factors that impact on QoL in CU patients.
Subjects and methods This interdisciplinary interview/questionnaire‐based study included 100 patients admitted to a University Hospital Dermatology Department for the identification of underlying causes of CU; 96 healthy subjects matched for age and sex were used as controls. QoL was assessed using Skindex‐29, a validated instrument to measure the effects of skin disease on overall QoL (composite score) and three defined QoL aspects (emotions, symptoms, functioning).
Results CU patients exhibited markedly reduced overall QoL compared with healthy control subjects. CU had distinct effects on the three QoL aspects assessed (functioning = emotions > symptoms). The age or sex of patients, the absence or presence of angio‐oedemas, and the duration or cause of CU did not significantly influence QoL impairment. Interestingly, psychiatric comorbidity (depression, anxiety, somatoform disorders) was associated with a more pronounced reduction of QoL compared with CU patients without a psychiatric diagnosis and the severity of psychiatric disease was found to correlate with QoL impairment.
Conclusions Our data confirm that overall QoL is markedly reduced in CU patients. Social functioning and emotions were found to be the areas of QoL most affected in CU patients. Psychiatric comorbidity significantly increased QoL impairment, whereas QoL in CU patients was not significantly affected by age or sex, the absence or presence of angio‐oedema, or the course or cause of CU.
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