Comparative Effectiveness of Integrated Peer Support and Clinical Staffing Models for Community-Based Residential Mental Health Rehabilitation: A Prospective Observational Study.

This observational study compared the outcomes of consumers receiving community-based residential mental health rehabilitation support in Australia under a clinical staffing model and an integrated staffing model where Peer Support Workers are the majority component of the staffing profile. Reliable and clinically significant (RCS) change between admission and discharge in functional and clinical assessment measures were compared for consumers receiving care under the clinical (n = 52) and integrated (n = 93) staffing models. Covariate analyses examined the impact of known confounders on the outcomes of the staffing model groups. No statistically significant differences in RCS improvement were identified between the staffing models. However, logistic regression modelling showed that consumers admitted under the integrated staffing model were more likely to experience reliable improvement in general psychiatric symptoms and social functioning. The findings support the clinical and integrated staffing models achieving at least equivalent outcomes for community-based residential rehabilitation services consumers.

Disease activity and treatment efficacy using patient-level Psoriasis Area and Severity Index scores from tildrakizumab phase 3 clinical trials.

BACKGROUND: It is unclear whether primary efficacy outcomes in plaque psoriasis clinical trials represent residual disease during treatment. OBJECTIVES: To evaluate supplementing dichotomous efficacy with residual disease activity. METHODS: This post hoc analysis used pooled, patient-level data after tildrakizumab 100 mg (N = 616) or placebo (N = 309) treatment from reSURFACE 1/2 (NCT01722331/NCT01729754) phase 3 clinical trials of patients with moderate to severe plaque psoriasis. RESULTS: Median baseline Psoriasis Area and Severity Index (PASI) was 17.9 for patients receiving tildrakizumab 100 mg. At Week 12, median PASI was 2.9, whereas dichotomous PASI 90 response rate was 36.9%, and absolute PASI <5.0, <3.0, and <1.0 were 64.0%, 50.8%, and 23.3%, respectively. At Week 28, median PASI was 1.7, whereas PASI 90 response rate was 51.9%, and absolute PASI <5.0, <3.0, and <1.0 were 75.3%, 62.8%, and 38.0%, respectively. Dermatology Life Quality Index and PASI scores were correlated through Week 28 (r = 0.51, p ≤ .0001). CONCLUSIONS: Disease activity was more reliably estimated by PASI scores than percentage PASI improvement; this may partially explain efficacy disparities between clinical trials and practice. These results suggest supplementing dichotomous PASI improvement with PASI scores and consideration of patient treatment goals could facilitate clinical decisions.

Community-care unit model of residential mental health rehabilitation services in Queensland, Australia: predicting outcomes of consumers 1-year post discharge.

AIMS: Community care units (CCUs) are a model of residential psychiatric rehabilitation aiming to improve the independence and community functioning of people with severe and persistent mental illness. This study examined factors predicting improvement in outcomes among CCU consumers. METHODS: Hierarchical regression using data from a retrospective cohort (N = 501) of all consumers admitted to five CCUs in Queensland, Australia between 2005 and 2014. The primary outcome was changed in mental health and social functioning (Health of the Nation Outcome Scale). Secondary outcomes were disability (Life Skills Profile-16), service use, accommodation instability, and involuntary treatment. Potential predictors covered service, consumer, and treatment characteristics. Group-level and individualised change were assessed between the year pre-admission and post-discharge. Where relevant and available, the reliable and clinically significant (RCS) change was assessed by comparison with a normative sample. RESULTS: Group-level analyses showed statistically significant improvements in mental health and social functioning, and reductions in psychiatry-related bed-days, emergency department (ED) presentations and involuntary treatment. There were no significant changes in disability or accommodation instability. A total of 54.7% of consumers demonstrated reliable improvement in mental health and social functioning, and 43.0% showed RCS improvement. The majority (60.6%) showed a reliable improvement in psychiatry-related bed-use; a minority demonstrated reliable improvement in ED presentations (12.5%). Significant predictors of improvement included variables related to the CCU care (e.g. episode duration), consumer characteristics (e.g. primary diagnosis) and treatment variables (e.g. psychiatry-related bed-days pre-admission). Higher baseline impairment in mental health and social functioning (ß = 1.12) and longer episodes of CCU care (ß = 1.03) increased the likelihood of RCS improvement in mental health and social functioning. CONCLUSIONS: CCU care was followed by reliable improvements in relevant outcomes for many consumers. Consumers with poorer mental health and social functioning, and a longer episode of CCU care were more likely to make RCS improvements in mental health and social functioning.

Management of psoriasis as a systemic disease: what is the evidence?

BACKGROUND: Psoriasis is a chronic, systemic immune-mediated disease characterized by development of erythematous, indurated, scaly, pruritic and often painful skin plaques. Psoriasis pathogenesis is driven by proinflammatory cytokines and psoriasis is associated with increased risk for comorbidities, including, but not limited to, psoriatic arthritis, cardiovascular disease, diabetes mellitus, obesity, inflammatory bowel disease and nonalcoholic fatty liver disease compared with the general population. OBJECTIVES: To explore the pathophysiological relationship between psoriasis and its common comorbidities and discuss the need for new treatment paradigms that include strategies to reduce systemic inflammation in patients with moderate-to-severe psoriasis. METHODS: This narrative review summarizes the published evidence related to the ability of biological therapies to ameliorate the consequences of systemic inflammation in patients with psoriasis. RESULTS: Current evidence suggests that preventing damage associated with inflammation, and preventing development of future inflammatory damage and comorbidities, may be a potentially achievable treatment goal for many patients with moderate-to-severe plaque psoriasis when biological therapies are utilized early in the disease. Encouraging data from recent studies suggest that the loftier goal of reversing existing inflammatory damage and improving signs and symptoms of inflammatory comorbidities could also possibly be attainable. CONCLUSIONS: Results from ongoing prospective studies regarding the effects of biologics on markers of systemic inflammation in patients with psoriasis will strengthen the clinical evidence base that can be used to inform treatment decisions for patients with moderate-to-severe psoriasis. What's already known about this topic? Psoriasis is a systemic inflammatory disease and treatments are needed to optimize patient outcomes. What does this study add? This review discusses new psoriasis treatment paradigms that may potentially reduce effects of systemic inflammation. Evidence demonstrating that biological treatment may prevent or reverse inflammatory damage associated with psoriasis comorbidities is reviewed.

Tofacitinib in patients with moderate-to-severe chronic plaque psoriasis: long-term safety and efficacy in an open-label extension study.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor. Final safety and efficacy data from an open-label extension study of tofacitinib in psoriasis are reported. OBJECTIVES: To evaluate the long-term safety and durability of efficacy of tofacitinib in adults with moderate-to-severe chronic plaque psoriasis. METHODS: Eligible patients who completed qualifying phase II/III tofacitinib studies received tofacitinib 10 mg twice daily (q12h) until month 3; subsequently, the dose could be adjusted by investigators to either 5 or 10 mg q12h. Adverse events (AEs) are reported up to month 66 and laboratory data up to month 54. Efficacy end points up to month 54 included Physician's Global Assessment of 'clear' or 'almost clear' (PGA response) and 75% improvement in Psoriasis Area and Severity Index (PASI 75). RESULTS: Overall, 2867 patients received tofacitinib, with a median treatment duration of 35·6 months. Adverse events (AEs) and serious AEs were reported in 82·5% and 13·7% of patients, respectively; 13·9% of patients discontinued owing to AEs; and 29 patients died. Incidence rates (patients with event/100 patient-years) were 1·16 for serious infections, 0·67 for malignancies and 0·26 for major adverse cardiovascular events. After initial changes in qualifying studies, most laboratory parameters were generally stable over 54 months. PGA response was achieved by 52-62% of patients and PASI 75 by 56-74% of patients at each study visit through month 54. CONCLUSIONS: In patients with psoriasis, the safety profile of tofacitinib over 66 months was similar to previous reports in phase III studies and efficacy was sustained through 54 months (NCT01163253).

Ixekizumab treatment for psoriasis: integrated efficacy analysis of three double-blinded, controlled studies (UNCOVER-1, UNCOVER-2, UNCOVER-3).

BACKGROUND: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A, is approved for the treatment of moderate-to-severe psoriasis. OBJECTIVES: This analysis represents an overview of the efficacy outcomes from three phase III psoriasis studies. METHODS: Data were integrated from the 12-week induction period of three studies in which patients received ixekizumab 80 mg every 2 weeks (IXE Q2W; n = 1169) or every 4 weeks (IXE Q4W; n = 1165) after an initial 160-mg dose for both; etanercept (50 mg biweekly; n = 740; two studies) or placebo (n = 792). The coprimary end points were the percentages of patients with response of static Physician's Global Assessment (sPGA; score 0 or 1) and ≥ 75% improvement in baseline Psoriasis Area and Severity Index (PASI 75) at week 12. Response rates were compared between treatments using the Cochran-Mantel-Haenszel test stratified by study. Treatment comparisons with placebo included data from three studies, whereas etanercept comparisons were based on two studies. RESULTS: Ixekizumab treatment was superior to placebo (P < 0·001) and etanercept (P < 0·001) on sPGA (0, 1) and PASI 75, with significant differences in PASI improvement at week 1. With IXE Q2W, at week 12, the frequencies of patients achieving PASI 75, 90 and 100 were nearly 90%, 70% and 40%, respectively. Ixekizumab-treated patients showed significantly greater improvement vs. placebo and etanercept in percentage body surface area involvement and fingernail psoriasis. IXE Q2W was superior to IXE Q4W on all treatment outcomes. CONCLUSIONS: Ixekizumab therapy at both dosing regimens demonstrated rapid onset and superior efficacy to placebo and etanercept, with IXE Q2W providing better outcomes than IXE Q4W during the first 12 weeks of treatment.

Treatment outcomes with ixekizumab in patients with moderate-to-severe psoriasis who have or have not received prior biological therapies: an integrated analysis of two Phase III randomized studies.

BACKGROUND: Biologics are effective for the treatment of psoriasis. However, treatment outcomes may differ among biologic-naive patients and those switched from previous biological therapies. OBJECTIVES: The study's objective was to investigate efficacy and safety of ixekizumab, a high-affinity anti-interleukin-17A antibody, in patients with psoriasis with and without previous exposure to biologics. METHODS: Data were integrated from the 12-week induction phase of two etanercept-controlled Phase III trials. Patients received 80 mg ixekizumab every 2 weeks (IXE Q2W; N = 736) or every 4 weeks (IXE Q4W; N = 733) following a 160-mg starting dose, or placebo (N = 361). Etanercept (50 mg twice weekly; N = 740) was administered as active control. Psoriasis Area and Severity Index (PASI) 75, PASI 90 and PASI 100 response rates at week 12 were evaluated in patients with or without previous exposure to biologics. Treatment effects were analysed with the Cochran-Mantel-Haenszel test stratified by study; missing values were imputed as non-response. RESULTS: Overall, 497 (19.3%) patients had prior exposure to biologics and 2073 (80.7%) were naive to biologic therapy. PASI 75 was achieved by 91.5% of biologic-experienced patients and 87.7% of biologic-naive patients for IXE Q2W, 76.2% and 82.2% for IXE Q4W, respectively, and 34.6% and 50.7%, respectively, for etanercept. Higher response rates favouring each ixekizumab dose over etanercept within subgroups were also seen regarding PASI 90 and PASI 100. CONCLUSIONS: Contrary to etanercept, the efficacy of ixekizumab was similarly high in patients with and without previous exposure to biologics when administered 80 mg every 2 weeks.

Satisfaction with current psoriasis treatment: misalignment between physician and patient perceptions.

Psoriasis patients often report dissatisfaction with treatment. However, the extent to which patients and their treating dermatologists are aligned regarding satisfaction with psoriasis therapy is largely unknown. This was explored using data derived from the Adelphi 2011/2013 Psoriasis Disease Specific Programmes, two real world surveys of US dermatologists and their patients. Physicians and patients independently reported their satisfaction with psoriasis control (satisfied, dissatisfied). Two levels of satisfaction alignment between physician and patient responses were constructed: aligned (same responses) and misaligned (different responses). In addition, dermatologists provided patient treatment history and disease/symptom severity whereas patients reported data on health-related quality of life (HRQoL), using the EuroQOL 5-Dimension Health Questionnaire (EQ-5D) and Dermatology Life Quality Index (DLQI), and work productivity using the Work Productivity Activity index (WPAI). Multivariate regressions were employed to examine the relationship between satisfaction alignment, overall disease and symptom severity, HRQoL, and work productivity controlling for differences in patient demographics and comorbidities.From 627 paired dermatologist and psoriasis patient records, 512 (81.7%) and 115 (18.3%) cases fell into the 'aligned' and 'misaligned' groups, respectively. Compared with patients in the aligned group, those in the misaligned group had more moderate to severe psoriasis (82.3% vs. 43.7%), moderate to severe itching (45.6% vs. 27.8%), pain (23.0% vs. 10.6%), and scaling (54.8% vs. 36.1%), and had lower current biologics use (27.0% vs. 42%) (all p<0.05). The misaligned group was associated with reduced HRQoL (lower EQ-5D score: 0.86 vs. 0.91; higher DLQI score: 7.06 vs. 4.23) and greater work productivity loss (higher WPAI scores: 18.27 vs. 11.43) (all p<0.05). Multivariate analyses confirmed these results (p<0.05). Almost 1 in 5 patients were misaligned with their dermatologist's level of satisfaction with their psoriasis treatment; misalignment was associated with increased disease and symptom severity, reduced HRQoL, and reduced work productivity.

Impact of psoriasis flare and remission on quality of life and work productivity: a real-world study in the USA.

Although psoriasis patients often report a negative impact on health-related quality of life (HRQoL) and work productivity, less is known about how disease burden varies between periods of flare and remission. The aim of this study was tocompare HRQoL and work productivity by disease activity level. Data were extracted from Adelphi 2011/2013 Disease Specific Programmes, two real world surveys of US dermatologists and psoriasis patients. HRQoL was measured using the EuroQOL 5-Dimension Health Questionnaire (EQ-5D) and Dermatology Life Quality Index (DLQI). Work productivity was measured using the Work Productivity Activity index (WPAI). Three levels of disease activity were constructed based on physician reports: remission, active not flaring, active, and flaring. Multivariable regression analyses explored the relationship between disease activity, HRQoL and work productivity, controlling for differences in demographics and comorbidities. Out of 681 psoriasis patients 24% were in remission, 62% had active disease without flaring, and 15% experienced active disease and were currently flaring. Greater disease activity was associated with worse HRQoL. EQ-5D scores decreased with more active disease (remission vs. active not flaring vs. active and flaring: 0.93 vs. 0.90 vs. 0.82; p<0.05), while DLQI scores increased (remission vs. active not flaring vs. active and flaring: 2.0 vs. 5.00 vs. 8.7; p<0.05). WPAI scores increased with disease activity indicating increased productivity loss (remission vs. active not flaring vs. active and flaring: 5.9 vs. 14.8 vs. 26.9; p<0.05). The same trends were confirmed by multivariable regression analyses.

Visualization of atherosclerosis as detected by coronary artery calcium and carotid intima-media thickness reveals significant atherosclerosis in a cross-sectional study of psoriasis patients in a tertiary care center.

BACKGROUND: Psoriasis is a chronic inflammatory disease of the skin and joints that may also have systemic inflammatory effects, including the development of cardiovascular disease (CVD). Multiple epidemiologic studies have demonstrated increased rates of CVD in psoriasis patients, although a causal link has not been established. A growing body of evidence suggests that sub-clinical systemic inflammation may develop in psoriasis patients, even from a young age. We aimed to evaluate the prevalence of atherosclerosis and identify specific clinical risk factors associated with early vascular inflammation. METHODS: We conducted a cross-sectional study of a tertiary care cohort of psoriasis patients using coronary artery calcium (CAC) score and carotid intima-media thickness (CIMT) to detect atherosclerosis, along with high sensitivity C-reactive protein (hsCRP) to measure inflammation. Psoriasis patients and controls were recruited from our tertiary care dermatology clinic. Presence of atherosclerosis was defined using validated numeric values within CAC and CIMT imaging. Descriptive data comparing groups was analyzed using Welch's t test and Pearson Chi square tests. Logistic regression was used to analyze clinical factors associated with atherosclerosis, and linear regression to evaluate the relationship between psoriasis and hsCRP. RESULTS: 296 patients were enrolled, with 283 (207 psoriatic and 76 controls) having all data for the hsCRP and atherosclerosis analysis. Atherosclerosis was found in 67.6 % of psoriasis subjects versus 52.6 % of controls; Psoriasis patients were found to have a 2.67-fold higher odds of having atherosclerosis compared to controls [95 % CI (1.2, 5.92); p = 0.016], after adjusting for age, gender, race, BMI, smoking, HDL and hsCRP. In addition, a non-significant trend was found between HsCRP and psoriasis severity, as measured by PASI, PGA, or BSA, again after adjusting for confounders. CONCLUSIONS: A tertiary care cohort of psoriasis patients have a high prevalence of early atherosclerosis, increased hsCRP, and psoriasis remains a risk factor for the presence of atherosclerosis even after adjustment of key confounding clinical factors. Psoriasis may contribute to an accelerated systemic inflammatory cascade resulting in increased risk of CVD and CV events.

Patient satisfaction with current psoriasis treatment: a real-world study in the USA.

Psoriasis patients often report dissatisfaction with treatment. However, it is less clear how the severity of key psoriasis symptoms (painful skin, itching, and scaling) as well as overall disease severity influence patient dissatisfaction levels. Using the Adelphi 2011/2013 Psoriasis Disease Specific Programmes, two "real world" surveys of US dermatologists and their patients, patient satisfaction was evaluated. Dermatologists provided data on disease characteristics, while patients indicated their satisfaction with existing treatment. Physician-reported severity (none, mild, moderate/severe) of psoriasis-related itching, pain, and scaling, overall disease severity (mild, moderate and severe) and therapy type were compared by patient satisfaction levels (satisfied vs. dissatisfied). Multivariate regressions examined the relationship between patient satisfaction, clinical symptoms, and psoriasis overall disease severity, controlling for differences in patient demographics and comorbidities. The sample comprised 633 psoriasis patients (56% male) with a mean age of 45. Overall, 18% of patients reported dissatisfaction with their psoriasis treatment. Dissatisfied patients were more likely to have moderate (65% vs. 40%) or severe (21% vs 3%) psoriasis compared to patients who were satisfied (both p<0.05). Dissatisfied patients were also more likely to have more severe pain (30% moderate-to-severe pain vs. 9%), more severe itching (61% moderate-to-severe itching vs. 25%), and more severe scaling (68% moderate-to-severe scaling vs. 33%) than satisfied patients (all p< 0.05). Multivariate analyses confirmed these results. Clinicians should be aware that some psoriasis patients, especially those with severe overall disease or symptoms, may be dissatisfied and are in need of better treatment.

Relationship between psoriasis severity, clinical symptoms, quality of life and work productivity among patients in the USA.

BACKGROUND: Psoriasis is a chronic disease, and many patients experience itching, painful skin and scaling. The relationship between psoriasis severity and symptom severity, quality of life (QoL) and work productivity is not fully understood. AIM: To examine how QoL, work productivity and clinical symptoms vary between patients with mild, moderate and severe psoriasis. METHODS: During a recent US survey, dermatologists provided information on overall disease severity, symptom severity and comorbidities. Patients with psoriasis completed QoL and work productivity instruments: the EuroQoL 5-Dimension Health (EQ-5D) questionnaire, the Dermatology Life Quality Index (DLQI), and the Work Productivity and Activity Impairment (WPAI) questionnaire. Multivariate regression was used to explore the relationship between these outcome variables and psoriasis severity, controlling for differences in demographics and comorbidities. RESULTS: The study analysed 694 patients (55% male; mean age: 44 years); 48%, 46% and 6% had mild, moderate and severe psoriasis, respectively. Scaling was the most common symptom, which was experienced by 82% of patients, followed by itching (73%) and pain (32%). Increased psoriasis severity was associated with increased itching, pain and scaling, and with reduced QoL (decrease in EQ-5D scores: moderate vs. mild -0.04, severe vs. mild -0.18; increase in DLQI: moderate vs. mild 2.97, severe vs. mild 7.95). WPAI scores increased with severity, indicating greater impairment (moderate vs. mild: 11.77, severe vs. mild 18.73). CONCLUSIONS: Patients with more severe psoriasis experienced more severe symptoms and had a greater reduction in QoL and work productivity. It is important that physicians recognize the impact of severe disease on patients' lives and take steps to address this.

Increased severity of itching, pain, and scaling in psoriasis patients is associated with increased disease severity, reduced quality of life, and reduced work productivity.

BACKGROUND: Psoriasis patients report that this disease can impact on their health-related quality of life (HR-QoL) and work productivity. It is important to understand how this is influenced by the clinical characteristics of psoriasis such as symptom severity. Common symptoms include itching, pain, and scaling but the psychosocial impact these features have on patients is not well understood. OBJECTIVE: To explore the impact of psoriasis symptoms (itching, pain, and scaling) on HR-QoL and work productivity. METHOD: Data were extracted from the Adelphi 2011 and 2013 Psoriasis Disease Specific Programmes - two real world surveys of US dermatologists and their psoriasis patients.  HR-QoL was measured using the Dermatology Life Quality Index (DLQI) and EuroQOL 5-Dimension Health Questionnaire (EQ-5D). Work productivity loss was measured by the Work Productivity and Activity Impairment (WPAI) questionnaire. The impact of symptom severity (none, mild, moderate/severe) for itching, pain, and scaling on DLQI, EQ-5D, and WPAI scores were examined, controlling for differences in demographics and co-morbidities. RESULTS: Patient mean age was 44 years and 55% were male. Moderate/severe itching, pain, and scaling were experienced by 33%, 13%, and 41% of patients, respectively. Controlling for differences in demographics and co-morbidities, increased symptom severity was associated with reduced HR-QoL. Accordingly, EQ-5D scores decreased with itching severity (moderate/severe vs. none: -0.07; 95% confidence interval [CI] =-0.09, -0.04), whereas DLQI scores increased (moderate/severe versus none: 4.9; CI = 3.9, 5.9) (both p<0.05). WPAI scores increased with itching severity, indicating increased work productivity loss (moderate/severe versus none: 17.6, CI = 11.8, 23.5, p<0.05). The same pattern was observed for pain and scaling. CONCLUSIONS: Among the patients studied, increased severity of psoriasis-related itching, pain, and scaling was associated with reduced health-related QoL and work productivity.

Long-term efficacy and safety of ustekinumab, with and without dosing adjustment, in patients with moderate-to-severe psoriasis: results from the PHOENIX 2 study through 5 years of follow-up.

BACKGROUND: Evaluation of the dosing flexibility and long-term efficacy of biological agents is limited. OBJECTIVES: To evaluate the long-term efficacy and safety of ustekinumab with and without dosing adjustment in the 5-year PHOENIX 2 study. METHODS: Patients were randomized to placebo or ustekinumab (45 or 90 mg) at weeks 0, 4, then every 12 weeks; patients receiving placebo crossed-over at week 12. Dosing adjustments were permitted at/beyond week 28 for early adjusters (weeks 28 or 40 per response); late adjusters (during long-term extension per investigator judgement); and nonadjusters (maintained randomized treatment throughout the study). Efficacy and safety were evaluated through weeks 244 and 264, respectively. RESULTS: In the overall population, 70% (849 of 1212) of ustekinumab-treated patients completed treatment through week 244, with high proportions of patients responding to the 45-mg and 90-mg doses, respectively: 75% improvement in Psoriasis Area and Severity Index (PASI 75) (76·5% and 78·6%) and PASI 90 (50·0% and 55·5%). Approximately 20% of patients were early adjusters, 30% were late adjusters and 50% were nonadjusters. Approximately half of the late adjusters initiated adjustments after already achieving PASI 75. Improved response was generally observed following dosing adjustments. Through week 264, safety event rates did not increase and event rates were generally comparable between dose groups and between patients with and without dosing adjustment. CONCLUSIONS: Treatment with ustekinumab for up to 5 years was safe and effective. Improved response was generally demonstrated following dosing adjustments; further investigations are required to quantify actual incremental benefits. The results also suggest that some patients may desire treatment goals beyond PASI 75.

Efficacy and tolerability of three different doses of oral pimecrolimus in the treatment of moderate to severe atopic dermatitis: a randomized controlled trial.

BACKGROUND: Adult atopic dermatitis (AD) can seriously affect quality of life of patients and their families, and patients' disease is frequently not satisfactorily controlled with topical therapy. There is a need for alternatives to topical treatment in patients with moderate to severe AD. OBJECTIVES: To investigate the efficacy and safety of oral pimecrolimus, and to determine the response to three different doses in the treatment of AD. METHODS: In a double-blind, placebo-controlled, parallel-group, dose-finding study, patients with moderate to severe AD were randomized to receive either placebo, or oral pimecrolimus 10, 20 or 30 mg twice daily. The study consisted of a pretreatment phase, a 12-week double-blind treatment phase, and a 12-week post-treatment phase. RESULTS: In total, 103 patients were randomized. A clear, dose-dependent therapeutic effect of pimecrolimus treatment was observed, with a statistically significant onset of efficacy at week 2 and the greatest reduction from baseline of the Eczema Area and Severity Index of 66.6% at week 7 in the 30 mg twice daily dose group. Oral pimecrolimus was well tolerated and there were no signs of nephrotoxicity or the induction of hypertension. CONCLUSIONS: These data demonstrate the clinically relevant efficacy and short-term safety of oral pimecrolimus in adults with moderate to severe AD. Longer-term studies in larger cohorts are now required.

New immunomodulating drugs in autoimmune blistering diseases.

The autoimmune blistering diseases are a fascinating group of diseases characterized by the presence of blisters involving the skin and mucous membranes. Understanding of the diagnosis, pathophysiology, and advances in treatment of these diseases has grown enormously in recent years. In this article, the author discusses the major clinical and immunopathologic findings in bullous pemphigoid, mucous membrane pemphigoid, epidermolysis bullosa acquisita, linea IgA bullous disease, and pemphigus. The article focuses on the therapeutic management of patients with autoimmune blistering diseases, including the appropriate treatment of patients, with particular emphasis on the use of immunomodulating and immunosuppresive agents.

Significant absorption of topical tacrolimus in 3 patients with Netherton syndrome.

BACKGROUND: Tacrolimus is a macrolide immunosuppressant approved in oral and intravenous formulations for primary immunosuppression in liver and kidney transplantation. Topical 0.1% tacrolimus ointment has recently been shown to be effective in atopic dermatitis for children as young as 2 years of age, with minimal systemic absorption. We describe 3 patients treated with topical 0.1% tacrolimus who developed significant systemic absorption. OBSERVATION: Three patients previously diagnosed as having Netherton syndrome were treated at different centers with 0.1% tacrolimus ointment twice daily. Two patients showed dramatic improvement. All patients were found to have tacrolimus blood levels within or above the established therapeutic trough range for oral tacrolimus in organ transplant recipients. None of these patients developed signs or symptoms of toxic effects of tacrolimus. CONCLUSIONS: Patients with Netherton syndrome have a skin barrier dysfunction that puts them at risk for increased percutaneous absorption. The Food and Drug Administration recently approved 0.1% tacrolimus ointment for the treatment of atopic dermatitis. Children with Netherton syndrome may be misdiagnosed as having atopic dermatitis. These children are at risk for marked systemic absorption and associated toxic effects. If topical tacrolimus is used in this setting, monitoring of serum tacrolimus levels is essential.

The impact of tacrolimus ointment on health-related quality of life of adult and pediatric patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis can have detrimental effects on health-related quality of life (QOL). OBJECTIVE: Our purpose was to examine the QOL impact of tacrolimus ointment in patients with atopic dermatitis. METHODS: The Dermatology Life Quality Index (DLQI), Children's DLQI (CDLQI), and Toddler QOL Survey were used to assess QOL in adults (16 years or older), children (5-15 years), and toddlers (2-4 years) enrolled in 12-week, randomized, double-blind studies comparing two concentrations of tacrolimus ointment (0.03% and 0.1%) versus vehicle ointment for treatment of atopic dermatitis. QOL was assessed at baseline, week 3, and week 12/early discontinuation. RESULTS: Of the 985 patients enrolled, 91.5% had evaluable QOL data. Among adults, both tacrolimus ointment groups experienced improved QOL relative to the vehicle control group for all QOL scales (P<.001). Among children and toddlers, both tacrolimus ointment groups demonstrated significant QOL improvements relative to the vehicle control group (P<.05) for all but the Personal Relationships scale in the 0.03% tacrolimus ointment group among children. CONCLUSION: Tacrolimus ointment is associated with significant QOL benefits in adults, children, and toddlers with atopic dermatitis.

Cicatricial pemphigoid.

UNLABELLED: Cicatricial pemphigoid (CP) is a heterogeneous group of rare, chronic, subepithelial blistering disorders of the mucous membranes and, occasionally, the skin, which can have serious and rarely fatal consequences. The most common clinical features are desquamative gingivitis, oral erosions, and conjunctival fibrosis. Skin lesions occur less frequently and may present as widespread vesicles and bullae, as in bullous pemphigoid (BP). In some patients, the scarring can be a source of significant morbidity because it can result in odynophagia, strictures of the upper aerodigestive tract, or corneal opacities leading to eventual blindness. This article is a comprehensive review and discusses clinical, pathologic, and pathophysiologic aspects of this group of disorders collectively known as CP. (J Am Acad Dermatol 2000;43:571-91.) LEARNING OBJECTIVE: At the conclusion of this learning activity, participants should be familiar with the clinical spectrum of CP, the histopathologic and immunopathologic characteristics, the differential diagnosis, the treatment, and the natural history of the disease. Furthermore, this learning activity should facilitate early diagnosis of CP and should promote the idea that the involvement of other specialists, including ophthalmologists, otolaryngologists, gastroenterologists, and oral medicine specialists, as appropriate, will aid in providing these patients with the highest quality of care.