Real-world effectiveness of adalimumab in patients with moderate-to-severe hidradenitis suppurativa: the 1-year SOLACE study.

BACKGROUND: Long-term, real-word data are needed to help manage patients with hidradenitis suppurativa (HS) through this recurrent, painful and debilitating disease. OBJECTIVES: To primarily measure real-world effectiveness of adalimumab in HS and to secondarily observe clinical course of HS in the light of patients' response. METHODS: In SOLACE, adults with moderate-to-severe HS in need for change in ongoing therapy were treated with adalimumab for up to 52 weeks as per physician's medical practice. Treatment effectiveness was measured by Hidradenitis Suppurativa Clinical Response (HiSCR). Inflammatory nodules, abscesses and draining fistulas were counted, Hurley stage was assessed, and disease severity was rated using the International HS Severity Scoring System (IHS4). A post hoc analysis further explored the HiSCR response by abscess and inflammatory nodule (AN) count at baseline (low, medium and high) and gender. Spontaneously reported safety events were collected. RESULTS: From 23 Canadian centres, 69% of the 138 patients achieved HiSCR at week 24, which increased to 82% and 75% at week 52 in patients with medium and high AN counts, respectively. Gender (4 times the odds for female) and age at HS onset (5% decrease with each additional year) had an effect on achieving HiSCR. Treatment with adalimumab led to an important decrease in number of lesions in responders, with most gains observed in inflammatory nodules, more frequently in the lower body area of patients in the high AN count group. The IHS4 scores of responders were substantially lowered, with a larger decrease in patients of the high AN count group. No new safety signal was detected. CONCLUSIONS: The effectiveness of adalimumab was maintained during this 1-year period, and an optimal gain was documented for patients with medium and high AN counts. These real-world data support a prompt treatment of HS patients and the use of IHS4 to monitor treatment.

Adalimumab medium-term dosing strategy in moderate-to-severe hidradenitis suppurativa: integrated results from the phase III randomized placebo-controlled PIONEER trials.

BACKGROUND: Weekly adalimumab (Humira® ) is approved for the treatment of hidradenitis suppurativa (HS) based on the 12-week placebo-controlled periods of the two phase III PIONEER trials. OBJECTIVES: Using PIONEER integrated trial results, we aimed to evaluate the optimal medium-term adalimumab maintenance dosing strategy for moderate-to-severe HS. METHODS: Each trial had two double-blind periods; 12-week Period A and 24-week Period B. Patients randomized to adalimumab 40 mg every week (ADAew) (Period A), were rerandomized in Period B to ADAew (ADAew/ew), ADA every other week (ADAew/eow), or placebo (ADAew/pbo). Placebo-randomized patients were reassigned in Period B to ADAew (PIONEER I) or placebo (PIONEER II). The primary outcome was HS Clinical Response (HiSCR). Patients who lost response during Period B were discontinued from the study and offered an option to enter the open-label extension (OLE) to receive ADAew. Results are reported across the two study periods, and data were combined from the two study periods and the OLE. RESULTS: For week-12 HiSCR achievers, the HiSCR week-36 rate was 48·1% (ADAew/ew) vs. 46·2% (ADAew/eow) and 32·1% (ADAew/pbo). Combining (post hoc) these patients with week-12 partial responders further differentiated outcomes in Period B (ADAew/ew 55·7% vs. ADAew/eow 40·0% and ADAew/pbo 30·1%). Period-B adverse-event rates were ADAew/ew 59·6% vs. ADAew/eow 57·4% and ADAew/pbo 65·0%. One patient (ADAew/ew) reported a serious infection. CONCLUSIONS: Weekly adalimumab treatment, effective throughout 36 weeks, was the optimal maintenance medium-term dosing regimen for this population. At least partial response after 12 weeks with continued weekly dosing had better outcomes than dose reduction or interruption. Patients who do not show at least a partial response to weekly adalimumab by week 12 are unlikely to benefit from continued therapy. No new safety risks were identified. What's already known about this topic? Hidradenitis suppurativa (HS) is a chronic inflammatory disease, commonly misinterpreted as an infection and treated with long-term antibiotic regimens or surgical incisions. Based on the chronicity of HS and the lack of evidence for efficacious and safe long-term HS treatments, it is important to evaluate medium- to long-term therapies for HS. Weekly adalimumab (Humira® ) is approved for the treatment of moderate-to-severe HS based on the two phase III PIONEER trials. What does this study add? This study pooled data from the two PIONEER trials, providing a more robust assessment of outcomes. After at least partial treatment success with weekly adalimumab short-term therapy (12 weeks), continuing weekly dosing during the subsequent 24 weeks had better outcomes than dose reduction or treatment interruption. Patients who do not show at least a partial response to weekly adalimumab by week 12 are unlikely to benefit from continued therapy.

Hidradenitis suppurativa/acne inversa: a practical framework for treatment optimization - systematic review and recommendations from the HS ALLIANCE working group.

Hidradenitis suppurativa (HS)/acne inversa is a debilitating chronic disease that remains poorly understood and difficult to manage. Clinical practice is variable, and there is a need for international, evidence-based and easily applicable consensus on HS management. We report here the findings of a systematic literature review, which were subsequently used as a basis for the development of international consensus recommendations for the management of patients with HS. A systematic literature review was performed for each of nine clinical questions in HS (defined by an expert steering committee), covering comorbidity assessment, therapy (medical, surgical and combinations) and response to treatment. Included articles underwent data extraction and were graded according to the Oxford Centre for Evidence-based Medicine criteria. Evidence-based recommendations were then drafted, refined and voted upon, using a modified Delphi process. Overall, 5310 articles were screened, 171 articles were analysed, and 65 were used to derive recommendations. These articles included six randomized controlled trials plus cohort studies and case series. The highest level of evidence concerned dosing recommendations for topical clindamycin in mild disease (with systemic tetracyclines for more frequent/widespread lesions) and biologic therapy (especially adalimumab) as second-line agents (following conventional therapy failure). Good-quality evidence was available for the hidradenitis suppurativa clinical response (HiSCR) as a dichotomous outcome measure in inflammatory areas under treatment. Lower-level evidence supported recommendations for topical triclosan and oral zinc in mild-to-moderate HS, systemic clindamycin and rifampicin in moderate HS and intravenous ertapenem in selected patients with more severe disease. Intralesional or systemic steroids may also be considered. Local surgical excision is suggested for mild-to-moderate HS, with wide excision for more extensive disease. Despite a paucity of good-quality data on management decisions in HS, this systematic review has enabled the development of robust and easily applicable clinical recommendations for international physicians based on graded evidence.

Effectiveness of systemic treatments for pyoderma gangrenosum: a systematic review of observational studies and clinical trials.

BACKGROUND: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis with substantial morbidity. There is no consensus on gold-standard treatments. OBJECTIVES: To review the effectiveness of systemic therapy for PG. METHODS: We searched six databases for 24 systemic therapies for PG. Primary outcomes were complete healing and clinical improvement; secondary outcomes were time to healing and adverse effects. RESULTS: We found 3326 citations and 375 articles underwent full-text review; 41 studies met the inclusion criteria. There were 704 participants in 26 retrospective cohort studies, three prospective cohort studies, seven case series, one case-control study, two open-label trials and two randomized controlled trials (RCTs). Systemic corticosteroids were the most studied (32 studies), followed by ciclosporin (21 studies), biologics (16 studies) and oral dapsone (11 studies). One RCT (STOP-GAP, n = 121) showed that prednisolone and ciclosporin were similar: 15-20% of patients showed complete healing at 6 weeks and 47% at 6 months. Another RCT (n = 30) found that infliximab was superior to placebo at 2 weeks (46% vs. 6% response), with a 21% complete healing rate at 6 weeks. Two uncontrolled trials showed 60% and 37% healing within 4 months for canakinumab and infliximab, respectively; other data suggest that patients with concurrent inflammatory bowel disease may benefit from biologics. The remaining studies were poor quality and had small sample sizes but supported the use of corticosteroids, ciclosporin and biologics. CONCLUSIONS: Systemic corticosteroids, ciclosporin, infliximab and canakinumab had the most evidence in treating PG. However, current literature is limited to small and lower-quality studies with substantial heterogeneity.

The prevalence of anxiety in patients with psoriasis: a systematic review of observational studies and clinical trials.

Psoriasis and anxiety are chronic conditions with significant morbidity and there is evidence that they may exacerbate one another. There is little data on the prevalence of anxiety in psoriasis and the effect of psoriasis treatment on comorbid anxiety. The objective of this study was to perform a systematic review of the literature to describe the prevalence and severity of clinical anxiety disorders or anxiety symptoms among adult patients with psoriasis and characterize the effect of anti-psoriatic interventions on clinical anxiety disorders or anxiety symptoms. We searched PubMed, EMBASE, and the Cochrane Database using search terms 'psoriasis' and 'anxiety'. Results were tabulated and verified by two independent reviewers. Meta-analyses were not performed due to heterogeneity of data. Of 213 publications identified, 938 194 patients from 15 papers were included. The mean age ranged from 31.9-59.4 years old, with a mean PASI score of 7.65-22.8 (reported by nine studies) and a body surface area involvement of 25.9-39.8% (reported by two studies). The prevalence of anxiety in patients with psoriasis was 7-48%, which was significantly higher than healthy controls in two of three studies (HR 1.29-1.31, P = 0.001 and OR 2.91 [95% CI, 2.01-4.21], P < 0.001). Four of five studies (n = 2029) demonstrated an improvement in anxiety symptoms with psoriasis treatment. This review demonstrates a high prevalence of anxiety of adult patients with psoriasis suggesting that patients would benefit from systematic screening. Although the data suggest that anxiety may be improved through various psoriasis treatments, larger prospective randomized trials are needed to confirm this effect.

Psoriasis and adverse pregnancy outcomes: a systematic review of observational studies.

Psoriasis is a chronic inflammatory disorder with significant physical and psychological sequelae. The majority of individuals experience disease onset in early adult life - for women this often occurs during their reproductive years. While some autoimmune diseases have been shown to affect pregnancy outcomes adversely, such a relationship has not been well studied in psoriasis. We searched PubMed, Embase and the Cochrane database for published articles examining psoriasis and adverse pregnancy outcomes, and included observational studies and clinical trials evaluating direct measures of maternal and fetal morbidity and mortality. Four of the nine included articles reported a statistically significant increase in the risk of at least one outcome, including spontaneous abortion, caesarean delivery, low birth weight, macrosomia, large-for-gestational age, and a composite outcome consisting of both prematurity and low birth weight. However, these associations were not always consistent across studies. Overall, there was no clear evidence of increased adverse outcomes in pregnant women with psoriasis.

Cardiovascular disease risk factors in patients with hidradenitis suppurativa: a systematic review and meta-analysis of observational studies.

Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating skin disease. The aim of the study was to systematically review the literature and critically answer the question: In patients with HS, do cardiovascular risk factors appear at a significantly higher rate compared with controls? The main search was conducted in Medline, Embase and the Cochrane Central Register. Studies eligible for inclusion were of case-control, cross-sectional and cohort design, and included comparison of any cardiovascular risk factor(s) in patients with HS with those of control groups. An I(2) value > 50% was considered to show substantial heterogeneity. In this case, DerSimonian and Laird random-effect models were considered to compute pooled odds ratios (OR). Otherwise, a fixed-effects model was suitable. Nine studies, with 6174 patients with HS and 24 993 controls, were included. Significant association of HS with obesity [OR 3·45, 95% confidence interval (CI) 2·20-5·38, P < 0·001], central obesity (OR 2·97, 95% CI 1·41-6·25, P = 0·004), active smoking (OR 4·34, 95% CI 2·48-7·60, P < 0·001), history of smoking (OR 6·34, 95% CI 2·41-16·68, P < 0·001), hypertriglyceridemia (OR 1·67, 95% CI 1·14-2·47, P = 0·009), low high-density lipoprotein (HDL) (OR 2·48, 95% CI 1·49-4·16, P < 0·001), diabetes (OR 2·85, 95% CI 1·34-6·08, P = 0·007) and metabolic syndrome (OR 2·22, 95% CI 1·62-3·06, P < 0·001) was detected. Associations were significant both in population and hospital patients with HS, with hospital HS groups having uniformly higher ORs than the population HS groups. Causality could not be assessed. Heterogeneity was substantial in all analyses. This systematic review indicated that cardiovascular risk factors appear at a significantly higher rate in patients with HS compared with controls. The need for screening of patients with HS for modifiable cardiovascular risks is emphasized.

Effect of biologics on depressive symptoms in patients with psoriasis: a systematic review.

BACKGROUND: Twenty to fifty percent of patients with psoriasis have depressive symptoms. OBJECTIVE: To describe the effects of biologics (tumour necrosis factor inhibitors [TNFi] or interleukin 12/23 inhibitors [IL-12/23i]) on depressive symptoms in patients with psoriasis. METHODS: Electronic databases were searched for randomized controlled trials (RCTs) examining the effects of biologics on depressive symptoms in adults with psoriasis. RESULTS: Of the 305 publications identified, three RCTs were included in a systematic review. In a trial evaluating ustekinumab, mean change in Hospital and Anxiety Depression Rating Scale at 24 weeks from baseline was 3.1 with ustekinumab (P < 0.001) vs. 0.21 with placebo (not significant). In a trial evaluating adalimumab, mean change in Zung Self-Rating Depression Scale at 12 weeks from baseline was -6.7 with adalimumab vs. -1.5 with placebo. In a trial evaluating etanercept, the between-group difference at 12 weeks in Beck Depression Inventory Scale was 1.8 (95% CI: 0.6, 2.90) in favour of etanercept over placebo. Limitations are that diagnostic criteria for depression were not used and scales and data from individual RCTs could not be combined. CONCLUSION: Adalimumab, etanercept and ustekinumab were associated with statistically significant reductions in depressive symptom scores using various scales in patients with moderate-to-severe psoriasis.

Demography, baseline disease characteristics and treatment history of patients with psoriasis enrolled in a multicentre, prospective, disease-based registry (PSOLAR).

BACKGROUND: Psoriasis is associated with several comorbidities and behavioural risk factors. OBJECTIVES: To evaluate demographic and disease characteristics in patients enrolled in the Psoriasis Longitudinal Assessment and Registry (PSOLAR). METHODS: PSOLAR is a global, prospective, longitudinal, disease-based registry that includes a postmarketing commitment to evaluate safety in patients with psoriasis. Enrolled patients had to be receiving, or be eligible to receive, conventional systemic or biological agents. Demographic/disease characteristics, medical histories, lifestyle risk factors and previous treatments are collected at enrolment. Efficacy and safety data are collected every 6 months for 8 years, and data are extracted annually. Selected parameters are evaluated by age quartile using post hoc analyses. RESULTS: As of 23 August 2012, 11 900 patients were enrolled at 301 sites in North America, Europe and Latin America. Over half of the PSOLAR population (54·7%) is male, with a mean age of 48·6 years and mean body mass index of 30·9 kg m(-2) at enrolment. Mean duration of disease at enrolment was 17·5 years, and mean Physician's Global Assessment score was 2·0. Psoriatic arthritis (35·5%) and cardiovascular diseases (38·2%) were highly prevalent. Diabetes mellitus type II was reported in 11·4% of patients. Depression and anxiety were noted in 14·7% and 11·1% of patients, respectively; 79·0% reported any alcohol use and 56·7% reported smoking or a history of smoking. The occurrence of most comorbidities, including cardiovascular disease and risk factors, increased with age. CONCLUSIONS: In the PSOLAR population, multiple and age-appropriate comorbidities are associated with psoriasis and may affect the selection of psoriasis treatments.

Experience with ustekinumab for the treatment of moderate to severe hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a severe chronic inflammatory follicular disease characterized by nodules and abscesses affecting apocrine gland-bearing regions. HS is not well-controlled with conventional medical therapies such as topical therapy, oral antibiotics and retinoids, however, abrogation of tumour necrosis factor-α (TNF-α) function has proven effective in some patients. OBJECTIVE: To assess the safety and efficacy of the interleukin-12/23 inhibitor, ustekinumab for treatment of HS in three patients with moderate-severe disease. METHODS: The subjects received 3-45 mg subcutaneous injections of ustekinumab at 0, 1 and 4 months. Improvement was assessed by the dermatology life quality index (DLQI), visual analogue scale of pain (VAS) and physician's global assessment (PGA) at each monthly visit. RESULTS: Prior to treatment, subjects had moderate-severe HS (Hurley stage II-III) with a DLQI score between 8 and 12. At 6 months, one patient showed complete disease remission, while a 25-49% improvement was seen in a second patient and no change in a third. A moderate but statistically significant relationship was observed between VAS and DLQI scores (r=0.75; P<0.01). CONCLUSION: Ustekinumab may provide a safe and effective new treatment strategy for HS in some patients. Interleukin 12/23 inhibition is a potential therapeutic option for patients in which other therapies prove ineffective.

Body fat percentage is associated with cardiometabolic dysregulation in BMI-defined normal weight subjects.

BACKGROUND AND AIMS: Nearly 25% of normal weight individuals display abnormal metabolic profiles associated with obesity. As a wide range in body fat percentage (%BF) exists for BMI-defined normal weight individuals, we investigated whether elevated %BF (determined using DXA) was associated with cardiometabolic dysregulation among 977 normal weight subjects (192 men, 785 women) from the Canadian province of Newfoundland and Labrador. METHODS AND RESULTS: BMI and %BF were measured after a 12-h fasting period. Cardiometabolic abnormalities considered included elevated triglyceride, glucose and hsCRP levels, decreased HDL cholesterol, insulin resistance, and hypertension. Subjects were classified as metabolically healthy (0 or 1 cardiometabolic abnormality) or abnormal (≥2 cardiometabolic abnormalities) and divided into sex-specific %BF tertiles as follows: low (≤15.2% men, ≤29.7% women), medium (15.3-20.7%% men, 29.8-34.9%% women) and high (≥20.8% men, ≥35.0% women). The prevalence of the metabolically abnormal phenotype was higher among medium and high %BF subjects (12.0% and 19.5%, respectively) compared to the low group (7.4%; p < 0.05). Furthermore, the odds of being metabolically abnormal were 1.61 (95% CI 0.94-2.77) for medium %BF subjects compared to the low group and nearly tripled for high %BF subjects (OR 2.73, 95% CI 1.63-4.86). ORs remained significant after further adjustment for waist circumference. CONCLUSION: Our findings indicate that those with elevated %BF are at increased risk of developing cardiometabolic disease despite having a normal BMI. Future development of adequate screening tools to identify these individuals is crucial to the prevention of obesity-associated disease.

Cumulative life course impairment in psoriasis: patient perception of disease-related impairment throughout the life course.

Psoriasis is associated with significant physical, psychological, social and economic burden, the cumulative effect of which may result in failure to achieve 'full life potential' in some patients, termed 'cumulative life course impairment' (CLCI). In this concept, the burden of stigmatization, and physical and psychological comorbidities (risk factors for cumulative impairment) and coping strategies and external factors (having potential moderating effects), interact to cause lifetime impairment. Components of CLCI are supported by cross-sectional data; however, the cumulative nature of impairment in patients with psoriasis is not yet established. Nonetheless, CLCI makes intuitive sense to many dermatologists who recognize the cumulative impact of psoriasis on the lives of some patients. This supplement explores the causes and mechanisms of CLCI qualitatively by presenting cases which are representative of typical patients with moderate-to-severe psoriasis. These cases demonstrate the effect of psoriasis in influencing major life-changing decisions and altering the course of patients' lives, preventing patients from attaining their life goals, pursuing their chosen career, gaining a desired educational level, developing social relationships, gaining full pleasure from family life or having children. All these patients believe that their lives would have taken a different course had they not had psoriasis. Additional research to determine how CLCI occurs and to identify the risk factors for cumulative impairment is required. Understanding the key risk factors for CLCI may help physicians identify patients who are more vulnerable to the cumulative impact of psoriasis, resulting in more appropriate treatment decisions earlier in the disease course.

Cyclosporine in the management of esophageal lichen planus.

Lichen planus (LP) is an uncommon disorder of unknown etiology, mostly affecting patients in their fifth and sixth decade of life. It is believed to be an autoimmune process involving T cells directed against basal keratinocytes. It affects the skin, nails, oral pharynx and genitals. Esophageal involvement is quite rare and can cause strictures, ulcerations and squamous cell cancer. The present article describes the case of a 54-year-old woman who was referred for assessment of dysphagia that initially occurred with solids, which then progressed to soft foods but spared liquids. The patient reported a weight loss of 9.1 kg. An esophagogastroduodenoscopy was performed and she was subsequently diagnosed with pill esophagitis. At the same time, she was also diagnosed with oral LP, with no involvement of the esophagus. She was treated with a proton pump inhibitor that resolved her gastrointestinal symptoms. The symptoms returned one year later and a repeat esophagogastroduodenoscopy revealed white plaques due to LP. She was treated with intermittent glucocorticoids. Diagnosis of esophageal LP is crucial for the proper treatment. Some patients may require systemic immunosuppression and mechanical dilation to prevent weight loss. Surveillance endoscopies should be performed to monitor for squamous cell cancer. Cyclosporine has been used for genital and oral LP, but the present case is the first in which it has been used successfully to treat esophageal LP.

Long-term prognosis in patients with psoriasis.

Psoriasis is a chronic, inflammatory, immune-mediated skin disease associated with substantial comorbidity. Traditional comorbid conditions include psychological/psychiatric disorders, psoriatic arthritis and inflammatory bowel disease. Increasingly, an association with metabolic dysfunction, including obesity and the metabolic syndrome, and cardiovascular disease, with consequent effects on morbidity and mortality, has been recognized in psoriasis. The underlying inflammatory mechanisms of both psoriasis and psoriasis-associated comorbidities involve mediation by proinflammatory T-helper type 1 cytokines. For effective management of psoriasis and related comorbidities, an integrated approach targeting both cutaneous and systemic inflammation may be beneficial, and strategies to improve overall management of the patient should be encouraged to reduce the disease burden. This paper discusses the emerging role of biological agents in this approach, and offers an appreciation of the role of existing anti-psoriasis and adjunctive therapies.

A review of biologic treatments for psoriasis with emphasis on infliximab.

Moderate-to-severe psoriasis is known to affect millions of people around the globe. This chronic disease substantially impacts patients by impairing their quality of life, causing psychosocial distress, and creating an ongoing financial burden. The biologics are the newest and most effective therapeutic weapon in the treatment of moderate-to-severe psoriasis and psoriatic arthritis that can significantly alter the course of the disease in a relatively short period of time. There is a need to review the recommended treatment guidelines for moderate- to-severe psoriasis and psoriatic arthritis as the perception and demands of patients are constantly changing. Real world experience with this class of drugs is expanding and more new biologics are becoming available.

Long-term safety and tolerability of pimecrolimus cream 1% and topical corticosteroids in adults with moderate to severe atopic dermatitis.

OBJECTIVE: This randomized, double-blind, multi-centre study compared the long-term safety and tolerability of pimecrolimus cream 1% and topical corticosteroids (TCS) in 658 adults with moderate-severe atopic dermatitis (AD). METHODS: Patients applied either pimecrolimus or TCS (i.e. 0.1% triamcinolone acetonide cream and/or 1% hydrocortisone acetate cream) twice daily to all affected areas until complete clearance or for up to 1 year. The study was approved by the institutional review board or ethics committee at each centre. RESULTS: A majority of patients treated with either pimecrolimus or TCS used the drug on a continuous basis over 1 year. In patients who had >30% of the body surface involved by AD, the incidence rate of all skin infections was significantly lower in the pimecrolimus group than in the TCS group (95% CI of the treatment difference: -25.3% to -3.4%). The most frequent application site reaction was burning (25.9% of patients on pimecrolimus and 10.9% on TCS), which was transient and mild-moderate in most cases. Three TCS-treated patients reported skin striae. There were no treatment-related serious or clinically significant systemic adverse events. Efficacy was better in patients on continuous TCS therapy, although patients completing the study were similarly well-controlled in both groups. About 42% of the pimecrolimus-treated patients were maintained for 1 year without TCS. CONCLUSION: Pimecrolimus demonstrated a favourable safety profile when used to treat adult patients with moderate-severe AD for up to 1 year. A significant proportion of patients could be maintained without TCS for a year.

A new calcipotriol/betamethasone formulation with rapid onset of action was superior to monotherapy with betamethasone dipropionate or calcipotriol in psoriasis vulgaris.

In this study, we compared a new combination ointment containing both calcipotriol and betamethasone dipropionate with betamethasone dipropionate ointment (Diprosone) and calcipotriol ointment (Daivonex) in patients with psoriasis vulgaris; 1106 patients were randomized to twice daily double-blind treatment with combination, betamethasone dipropionate or calcipotriol for 4 weeks. Patients then received twice daily calcipotriol, unblinded, for a further 4 weeks. Mean percentage change in PASI at end of the double-blind phase was -74.4 (combination group), -61.3 (betamethasone group) and -55.3 (calcipotriol group). Mean difference (95% Cl) combination-betamethasone was -13.1 (-16.9 to -9.3, p < 0.001) and for combination-calcipotriol -19.0 (-22.8 to -15.2, p <0.001). The differences in PASI were also statistically significant after 1 week. In the double-blind phase, 8.1% of patients (combination) reported lesional/ perilesional adverse reactions compared to 4.7% (betamethasone) and 12.0% (calcipotriol). In the combination group, mean PASI at the end of the double-blind phase was 2.5, and at end of the unblinded phase 3.6, compared with 3.9 and 4.1 (betamethasone) and 4.4 and 3.7 (calcipotriol). Calcipotriol/betamethasone combination is more effective and has a more rapid onset of action than either active constituent used alone, and is well tolerated. It is safe to transfer patients from combination to calcipotriol, with maintenance of clinical effect.

The treatment of moderate to severe psoriasis with a new anti-CD11a monoclonal antibody.

BACKGROUND: Anti-CD11a (hu1124) is a humanized monoclonal antibody directed against the CD11a subunit of LFA-1. This study investigated whether treatment with anti-CD11a antibody provides clinical benefit to patients with moderate to severe plaque psoriasis. METHODS: This was a double-blind, placebo-controlled, phase II, multicenter study. In total, 145 patients with minimum Psoriasis Area and Severity Index scores of 12 and affected body surface area of 10% or more were sequentially enrolled into low-dose (0.1 mg/kg, n = 22) or high-dose (0.3 mg/kg, n = 75) groups. Within groups, patients were randomized to treatment or placebo (n = 48) in a 2:1 ratio. Drug was administered intravenously at weekly intervals for 8 weeks. RESULTS: The percentage of subjects achieving more than 50% improvement in physician's global assessment at day 56 (1 week after final dose) was 15% and 48% for placebo and 0.3 mg/kg of drug, respectively (P =.002). A physician's global assessment of excellent (>75% improvement) was greater in the 0.3 mg/kg group versus placebo (25% vs 2%, P =.0003). Average Psoriasis Area and Severity Index scores at day 56 were 13.9 +/- 7.5 (placebo) and 10.9 +/- 8.4 (0.3 mg/kg) (P <.0001). Epidermal thickness was reduced in the 0.3 mg/kg group compared with the placebo group (37% vs 19%, P =.004). Treatment was well tolerated; mild to moderate flu-like complaints were the most common adverse events. White blood cell counts and lymphocyte counts transiently increased. Depletion of circulating lymphocytes did not occur. CONCLUSIONS: Anti-CD11a antibody administered intravenously in 8 weekly doses of 0.3 mg/kg was well tolerated and induced clinical and histologic improvements in psoriasis.