The Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD): The development and reliability testing of a novel clinical outcome measurement instrument for the severity of atopic dermatitis.

BACKGROUND: An Investigator Global Assessment (IGA) is recommended by health agencies for drug registration in atopic dermatitis (AD). Current IGA scales lack standardization. OBJECTIVES: To develop an IGA scale, training module, and clinical certification examination for use in AD trials; establish content validity; and assess reliability. METHODS: Expert dermatologists participated in the development of the validated IGA for AD (vIGA-ADTM). Reliability (interrater and intrarater) was assessed by 2 web-based surveys. Clinical certification for investigators consisted of a training module and examination. RESULTS: Expert consensus was achieved around a 5-point IGA scale including morphologic descriptions, and content validity was established. Survey 1 showed strong interrater reliability (Kendall's coefficient of concordance W [Kendall's W], 0.809; intraclass correlation [ICC], 0.817) and excellent agreement (weighted kappa, 0.857). Survey 2, completed 5 months after training of dermatologists, showed improvements in scale reliability (Kendall's W, 0.819; ICC, 0.852; weighted kappa, 0.889). In this study, 627 investigators completed vIGA-AD training and certification. LIMITATIONS: Ratings were assessed on photographs. CONCLUSION: A validated IGA scale and training module were developed with the intent of harmonizing assessment of disease severity in AD trials. Strong reliability and excellent agreement between assessments were observed.

Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis.

BACKGROUND: Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS: We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS: In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS: In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known. (Funded by Eli Lilly; UNCOVER-1, UNCOVER-2, and UNCOVER-3 ClinicalTrials.gov numbers NCT01474512, NCT01597245, and NCT01646177, respectively.).

A multi-item Physician Global Assessment scale to assess psoriasis disease severity: validation based on four phase III tofacitinib studies.

BACKGROUND: Several different Physician Global Assessment (PGA) versions have been used in clinical studies as a co-primary end point to evaluate psoriasis severity. Tofacitinib is an oral Janus kinase inhibitor. We performed an analysis of the PGA using data from studies of tofacitinib in moderate to severe chronic plaque psoriasis. METHODS: Data from 3641 patients with moderate to severe chronic plaque psoriasis, enrolled in one of four phase III tofacitinib studies (OPT Pivotal 1 and 2, OPT Compare and OPT Retreatment), were used to evaluate a three-item PGA scale. RESULTS: Confirmatory Factor Analyses showed that equal weighting of the three items (erythema, induration and scaling) was appropriate. The PGA demonstrated acceptable test-retest reliability (Intraclass Correlation Coefficient, 0.7) and internal consistency (Cronbach's Coefficient Alpha ≥ 0.9 at primary time points). The Clinically Important Difference was estimated as 0.55 (95% confidence interval: 0.546-0.563). Known-group validity was shown by demonstrating that PGA scores could discriminate between different degrees of disease severity. The PGA was significantly correlated with other clinical end points in the studies (Psoriasis Area and Severity Index, r = 0.75-0.79; Dermatology Life Quality Index, r = 0.44-0.57; Patient Global Assessment, r = 0.66-0.72). CONCLUSIONS: Consistent with previous findings from a phase II study, these results indicate that this PGA is a valid, reliable instrument for evaluating disease severity in clinical studies of psoriasis.

Ixekizumab treatment shows a neutral impact on cardiovascular parameters in patients with moderate-to-severe plaque psoriasis: Results from UNCOVER-1, UNCOVER-2, and UNCOVER-3.

BACKGROUND: The impact of ixekizumab treatment for psoriasis on cardiovascular-related parameters in patients is unknown. OBJECTIVE: To investigate cardiovascular-related parameters in patients with psoriasis treated with ixekizumab. METHODS: In phase 3 trials, patients with moderate-to-severe psoriasis were randomized and treated with placebo, ixekizumab, or etanercept during the induction period (weeks 0-12; UNCOVER-1, UNCOVER-2, and UNCOVER-3). At week 12, responders were rerandomized to receive placebo or ixekizumab through the maintenance period (weeks 12-60; UNCOVER-1 and UNCOVER-2). Laboratory measures (fasting lipid profiles, glucose level, or high-sensitivity C-reactive protein [hsCRP] level), weight, blood pressure, and electrocardiograms were obtained through 60 weeks. RESULTS: Baseline parameters were within normal ranges with the exception of elevated triglyceride and hsCRP levels. After maintenance dosing, no significant changes were observed versus placebo for total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, triglyceride, apolipoprotein A1, apolipoprotein B, or fasting glucose levels or for systolic/diastolic blood pressure at 60 weeks. Importantly, low-density lipoprotein-to-high-density lipoprotein ratios remained stable during the induction and maintenance periods. HsCRP concentrations were significantly reduced versus placebo at 12 weeks and remained reduced at 60 weeks, although not significantly. Although transient changes were observed for some parameters during the induction period, these changes did not persist into the maintenance period. LIMITATIONS: A lack of echocardiogram evaluations. CONCLUSIONS: Ixekizumab had a neutral impact on cardiovascular-related parameters in patients with psoriasis.

Maintenance of skin clearance with ixekizumab treatment of psoriasis: Three-year results from the UNCOVER-3 study.

BACKGROUND: Psoriasis is a chronic disease that may require long-term treatment. Ixekizumab (IXE), which is a high-affinity monoclonal antibody that selectively targets interleukin 17A, is an approved therapy for patients with moderate-to-severe plaque psoriasis. OBJECTIVE: To evaluate the efficacy and safety of IXE through 156 weeks from the UNCOVER-3 study in patients who were treated with the recommended dose regimen (160 mg of IXE at week 0, 80 mg every 2 weeks up to week 12, and 80 mg every 4 weeks thereafter). METHODS: Patients randomized to IXE every 2 weeks, IXE every 4 weeks, etanercept twice weekly, or placebo were switched to IXE every 4 weeks during the long-term extension period. Efficacy data were summarized by using the as-observed, multiple imputation, and modified nonresponder imputation methods. RESULTS: At week 156, 80.5% of patients had achieved at least a 75% improvement from baseline in their Psoriasis Area Severity Index (PASI) score, 66.0% had achived at least a 90% improvement from baseline in their PASI score, and 45.1% had achieved a 100% improvement from baseline in their PASI score with use of the modified nonresponder imputation method, and 97.2% and 86.2% of patients had achived at least a 75% improvement from baseline in their PASI score with use of the as-observed and multiple imputation methods, respectively. Similar response rates were observed in patients with baseline scalp, nail, or palmoplantar involvement. No new safety signals were identified through year 3. LIMITATIONS: No placebo or active comparison after week 12. CONCLUSION: IXE sustained high responses with clearance of skin and nail lesions, with no new safety concerns through 3 years.

Duration of Psoriatic Skin Disease as Risk Factor for Subsequent Onset of Psoriatic Arthritis.

It is unclear whether psoriasis is a progressive disease that requires early aggressive intervention. This population-based study identified patients with psoriasis and psoriatic arthritis (PsA). Survival analysis and Kaplan-Meier life table techniques were used. The study comprised 10,011 psoriasis patients (severe n = 4,618), and 1,269 patients also had PsA. Incidence of PsA increased with duration of cutaneous symptoms (p = 0.0001). Psoriasis diagnosed before age 20 or 30 years, respectively, suggested a lower risk of PsA than psoriasis diagnosed after age 50 years, yet age at first cutaneous symptoms did not predict development of PsA. No clear association with disease severity was found. PsA incidence appeared stable with longer duration of psoriasis, but further data are needed to firmly establish the relationship with age of psoriasis onset.

Safety and Tolerability of Ixekizumab: Integrated Analysis of Injection-Site Reactions from 11 Clinical Trials.

BACKGROUND: Injection-site reactions (ISRs) are reported with biologic therapies. The objective of this study was to comprehensively characterize ISRs among moderate-to-severe psoriasis patients treated with ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin (IL)-17A.

METHODS: ISRs are presented from UNCOVER-1, UNCOVER-2, and UNCOVER-3 (12 weeks) and all ixekizumab-exposed patients in 11 controlled and uncontrolled trials (156 weeks).

RESULTS: At week 12, reported ISR frequency with 80 mg ixekizumab every 2 weeks (IXE Q2W, 16.8%) was comparable with etanercept twice weekly (16.4%); both were significantly higher than placebo (3.3%). With IXE Q2W, ISRs were mild (12.3%), moderate (3.9%), or severe (0.7%), typically reported in the first 2 weeks (median onset, 6.6 days), and most commonly characterized as nonspecified, erythema, and pain. Generally, erythema onset was delayed, whereas pain occurred around drug administration. Discontinuation from ixekizumab due to ISRs (0.4%) occurred in the first 12 weeks. After 2 weeks, ISR frequency decreased and remained stable (≤4.2%) through week 156. No ISR-related serious adverse events were reported in ixekizumab-treated patients. ISR data were solicited if patients reported injection-associated events. Since nonspecified ISR was the most commonly reported term, specific types might be underreported.

CONCLUSIONS: ISRs have been reported with ixekizumab during clinical trials. These reactions are typically tolerable, manageable, and decrease over time.

Clinicaltrials.gov: NCT01474512 (UNCOVER-1); NCT01597245 (UNCOVER-2); NCT01646177 (UNCOVER-3); NCT01777191 (UNCOVER-A); NCT01624233 (UNCOVER-J); NCT01107457 (I1F-MC-RHAJ); NCT02561806 (I1F-MC-RHBS); NCT02387801 (I1F-US-RHBO);NCT02513550 (I1F-MC-RHBP); NCT02634801 (I1F-EW-RHBZ)

J Drugs Dermatol. 2018;17(2):200-206.

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Incidence and prevalence of psoriatic arthritis in Denmark: a nationwide register linkage study.

OBJECTIVES: To examine the incidence and temporal trends of psoriatic arthritis (PsA) in the general population in Denmark. METHODS: Using nationwide registry data, we estimated the number of patients with incident PsA within each 1-year period between 1997 and 2011 and calculated the rate of PsA cases within gender and age subgroups. Incidence rates were presented per 100 000 person-years. RESULTS: There was a female predominance ranging from 50.3% (1998) to 59.2% (2010), and the mean age at time of diagnosis was 47-50 years. We identified a total of 12 719 patients with PsA (prevalence=0.22%), including 9034 patients where the PsA diagnosis was made by a rheumatologist (prevalence=0.16%). Incidence rates of PsA (per 100 000 person-years) increased from 7.3 in 1997 to a peak incidence of 27.3 in 2010. Incidence rates were highest for women and patients aged 50-59 years, respectively. The use of systemic non-biologic agents, that is, methotrexate, leflunomide, ciclosporin or sulfasalazine increased over the 15-year study course and were used in 66.3% of all patients. Biologic agents (etanercept, infliximab, adalimumab, certolizumab pegol, golimumab or ustekinumab) were used in 17.7% of patients with PsA. CONCLUSIONS: We found a clear trend of rising PsA incidence on a national level. While the cause remains unclear, our findings might be explained by increased attention by patients and physicians.

Limited association between scalp psoriasis and psoriatic arthritis severity and treatment response.

OBJECTIVES: We evaluated whether scalp psoriasis (PsO) is associated with psoriatic arthritis (PsA) severity and/or with treatment response to etanercept. METHODS: Patients with moderate-to-severe PsO and active PsA received etanercept 50 mg once weekly for 24 weeks. Patients were stratified according to whether scalp PsO was present at baseline. Demographics and disease characteristics were compared at baseline and after 12 and 24 weeks of treatment with etanercept. RESULTS: Scalp PsO was present in 273/373 (73.2%) patients; they were significantly younger and a higher proportion were male versus those without scalp PsO. At baseline, the patient global assessment psoriasis score was significantly higher for patients with scalp PsO versus without (67.0 vs. 57.9, p<0.01); tender joint count was significantly higher for patients without scalp PsO (6.0 vs. 5.0, p<0.05). A higher proportion of patients without versus with scalp PsO achieved enthesitis ≤1 at Week 12 (91.5% vs. 81.7%, p<0.05) and dactylitis ≤1 at week 24 (93.9% vs. 85.6%, p<0.05). Patients with scalp PsO showed significantly greater improvements in fatigue and joint pain at weeks 12 and 24, and a greater proportion achieved a score ≤0.5 in the health assessment questionnaire at week 12 (65.2% vs. 53.0%, p<0.05). CONCLUSIONS: Scalp PsO was not clearly associated with PsA severity, and it did not affect treatment response. Patients without scalp PsO exhibited greater improvements in objective joint outcomes, whereas patients with scalp PsO experienced better outcomes in patient-reported outcomes.

Ten-year mortality is increased after hospitalization for atopic dermatitis compared with the general population, but reduced compared with psoriasis.

BACKGROUND: Psoriasis and atopic dermatitis (AD) are chronic inflammatory skin disorders. Mortality is increased in psoriasis, yet no studies on mortality in AD are currently available. OBJECTIVE: We investigated 10-year mortality after hospitalization for AD compared with psoriasis and the general population. METHODS: Between 1996 and 2002 all Danes aged 18 years or older with a first-time hospitalization as a result of AD or psoriasis and AD-matched healthy control subjects were examined in nationwide registers. Multivariable (adjusted for age, sex, socioeconomic status, Charlson Comorbidity Index score, smoking, and medication) hazard ratios were estimated by Cox regression. RESULTS: The study comprised 576 and 951 hospitalized patients with AD and psoriasis, respectively, with a maximum follow-up time of 10 years. During the study period, there were 65 and 286 deaths among patients with AD and psoriasis. Risk of death was decreased in patients with AD versus psoriasis (hazard ratio 0.75; 95% confidence interval 0.57-1.00), but higher than in general population control subjects (n = 5760) (hazard ratio 1.71; 95% confidence interval 1.20-2.44). Patients hospitalized with AD died on average 8.3 years younger than control subjects. LIMITATIONS: Lifestyle may have affected the risk. CONCLUSIONS: The 10-year mortality was significantly lower after hospitalization for AD compared with psoriasis, but increased when compared with the general population.

The relationship between duration of psoriasis, vascular inflammation, and cardiovascular events.

BACKGROUND: Psoriasis is associated with risk of cardiovascular (CV) disease (CVD) and a major adverse CV event (MACE). Whether psoriasis duration affects risk of vascular inflammation and MACEs has not been well characterized. OBJECTIVES: We utilized two resources to understand the effect of psoriasis duration on vascular disease and CV events: (1) a human imaging study and (2) a population-based study of CVD events. METHODS: First, patients with psoriasis (N = 190) underwent fludeoxyglucose F 18 positron emission tomography/computed tomography (duration effect reported as a ß-coefficient). Second, MACE risk was examined by using nationwide registries (adjusted hazard ratios in patients with psoriasis (n = 87,161) versus the general population (n = 4,234,793). RESULTS: In the human imaging study, patients were young, of low CV risk by traditional risk scores, and had a high prevalence of cardiometabolic diseases. Vascular inflammation by fludeoxyglucose F 18 positron emission tomography/computed tomography was significantly associated with disease duration (ß = 0.171, P = .002). In the population-based study, psoriasis duration had strong relationship with MACE risk (1.0% per additional year of psoriasis duration [hazard ratio, 1.010; 95% confidence interval, 1.007-1.013]). LIMITATIONS: These studies utilized observational data. CONCLUSION: We found detrimental effects of psoriasis duration on vascular inflammation and MACE, suggesting that cumulative duration of exposure to low-grade chronic inflammation may accelerate vascular disease development and MACEs. Providers should consider inquiring about duration of disease to counsel for heightened CVD risk in psoriasis.

Herpes zoster in psoriasis patients treated with tofacitinib.

BACKGROUND: Tofacitinib is an oral Janus kinase (JAK) inhibitor. Immunomodulatory therapies can increase the risk for herpes zoster (HZ) in patients with psoriasis. OBJECTIVE: To evaluate the relationship between tofacitinib use and HZ risk. METHODS: We used phases 2 and 3 and long-term extension (LTE) data from the tofacitinib development program in psoriasis to calculate HZ incidence rates (IR; events per 100 patient-years); potential HZ risk factors were evaluated using Cox-proportional hazard models. RESULTS: One hundred thirty (3.6%) patients on tofacitinib (IR 2.55), no patients on placebo, and 2 using etanercept (IR 2.68) developed HZ. Nine patients (7%) were hospitalized, and 8 (6%) had multidermatomal HZ; no encephalitis, visceral involvement, or deaths occurred. In total, 121 (93%) patients on tofacitinib continued or resumed use after HZ. HZ risk factors included Asian descent (hazard ratio [HR] 2.92), using tofacitinib 10 mg twice daily (vs 5 mg twice daily; HR 1.72), prior use of biologics (HR 1.72), and older age (HR 1.30). LIMITATIONS: Generalizability to other psoriasis populations might be limited. The effect of HZ vaccination was not studied. CONCLUSION: Tofacitinib is associated with increased HZ risk relative to placebo. Asian race, increasing age, higher dose, and prior biologic exposure are associated with heightened risk.

Short- and long-term safety outcomes with ixekizumab from 7 clinical trials in psoriasis: Etanercept comparisons and integrated data.

BACKGROUND: Safety of biologics is important when treating patients with psoriasis. OBJECTIVE: We sought to determine the safety of ixekizumab in psoriasis. METHODS: Integrated safety data are presented from a 12-week induction period, a 12- to 60-week maintenance period, and from all ixekizumab-treated patients from 7 clinical trials. Exposure-adjusted incidence rates (IRs) per 100 patient-years are reported. RESULTS: Overall, 4209 patients received ixekizumab (total exposure: 6480 patient-years). During the induction period, the IRs of patients experiencing 1 or more treatment-emergent adverse event (AE) were 251 and 236 among ixekizumab- and etanercept-treated patients, respectively, and for serious AEs was 8.3 in both groups. During maintenance, for ixekizumab, the IRs of treatment-emergent AEs and serious AEs were 100.4 and 7.8, respectively. Among all ixekizumab-treated patients from 7 trials, the IR of Candida infections was 2.5. The IRs of treatment-emergent AEs of special interest (including serious infections, malignancies, major adverse cardiovascular events) were comparable for ixekizumab and etanercept during the induction period. LIMITATIONS: Additional long-term data are required. CONCLUSION: Ixekizumab had an acceptable safety profile with no unexpected safety findings during ixekizumab maintenance in psoriasis.

Incidence and Prevalence of Psoriasis in Denmark.

The incidence and temporal trends of psoriasis in Denmark between 2003 and 2012 were examined. There was a female predominance ranging between 50.0% (2007) and 55.4% (2009), and the mean age at time of diagnosis was 47.7-58.7 years. A total of 126,055 patients with psoriasis (prevalence 2.2%) were identified. Incidence rates of psoriasis (per 100,000 person years) ranged from 107.5 in 2005 to a peak incidence of 199.5 in 2010. Incidence rates were higher for women, and patients aged 60-69 years, respectively. Use of systemic non-biologic agents, i.e. methotrexate, cyclosporine, retinoids, or psoralen plus ultraviolet A (PUVA) increased over the study course, and were used in 15.0% of all patients. Biologic agents (efalizumab, etanercept, infliximab, adalimumab, or ustekinumab) were utilized in 2.7% of patients. On a national level, incidence of psoriasis fluctuated during the 10-year study course. The relationship between psoriasis incidence and age appeared to be relatively linear, and disease prevalence was comparable to that in other European countries.

Family history predicts major adverse cardiovascular events (MACE) in young adults with psoriasis.

BACKGROUND: Patients with psoriasis may have increased risk of major adverse cardiovascular (CV) events (MACE), and a family history of CV disease (CVD) is an independent risk factor for MACE. OBJECTIVE: We investigated the risk of first-time MACE in patients with psoriasis with or without a family history of CVD. METHODS: Between January 1, 1997, and December 31, 2011, we identified 2,722,375 individuals, including 25,774 and 4504 patients with mild and severe psoriasis, through administrative registers. Incidence rate ratios were estimated by Poisson regression. RESULTS: Mean baseline age was 26.6 (SD 8.6) years. A family history of CVD was found among 16,080 (62.4%) and 3009 (66.8%) patients with mild and severe psoriasis, respectively. In patients with psoriasis and a family history of CVD, the adjusted incidence rate ratios (95% CI) of MACE were 1.28 (1.12-1.46) and 1.62 (1.14-2.30) for mild and severe disease, respectively. In patients with psoriasis but without a family history of CVD, there was no increased risk of MACE. LIMITATIONS: Results may not apply to late-onset psoriasis. CONCLUSIONS: A family history of CVD predicted the risk of first-time MACE in young adults with psoriasis. The findings call for increased focus on a family history of CVD in CV risk assessment of patients with psoriasis.

Tofacitinib improves pruritus and health-related quality of life up to 52 weeks: Results from 2 randomized phase III trials in patients with moderate to severe plaque psoriasis.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor that improves clinical measures of psoriasis. OBJECTIVE: We sought to assess patient-reported outcomes in tofacitinib-treated patients with moderate to severe plaque psoriasis over 52 weeks. METHODS: In 2 identical, phase III studies (Oral treatment for Psoriasis Trial Pivotal 1 [NCT01276639], n = 901, and Pivotal 2 [NCT01309737], n = 960), patients were randomized 2:2:1 to receive 5 or 10 mg of tofacitinib or placebo, twice daily. At week 16, placebo-treated patients were re-randomized to tofacitinib. Dermatology Life Quality Index score, Itch Severity Item score, Patient Global Assessment score, and patient satisfaction were assessed. RESULTS: Baseline Dermatology Life Quality Index score indicated substantial health-related quality of life impairment. At week 16, a greater proportion of patients achieved Dermatology Life Quality Index score of 1 or less (no effect of psoriasis on health-related quality of life) with tofacitinib 5 and 10 mg twice daily versus placebo (Oral treatment for Psoriasis Trial Pivotal 1/2: 26.7%/28.6% and 40.2%/48.2% vs 4.6%/6.0%, respectively; P < .0001); improvements were maintained through week 52. Similar patterns were observed with Patient Global Assessment. Improvements in itch were particularly rapid, observed 1 day after treatment initiation for both tofacitinib doses versus placebo (P < .05). At week 16, more patients were satisfied with tofacitinib versus placebo (P < .0001). LIMITATIONS: Clinical nonresponders discontinued at week 28. CONCLUSIONS: Tofacitinib demonstrated improvement in health-related quality of life and patient-reported symptoms that persisted over 52 weeks.

Tofacitinib, an oral Janus kinase inhibitor, for the treatment of chronic plaque psoriasis: Long-term efficacy and safety results from 2 randomized phase-III studies and 1 open-label long-term extension study.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor being investigated for psoriasis. OBJECTIVES: We sought to report longer-term tofacitinib efficacy and safety in patients with moderate to severe psoriasis. METHODS: Data from 2 identical phase-III studies, Oral-treatment Psoriasis Trial Pivotal 1 and 2, were pooled with data from these patients in an ongoing open-label long-term extension study. Patients (n = 1861) were randomized 2:2:1 to tofacitinib 5 mg, 10 mg, or placebo twice daily (BID). At week 16, placebo patients were rerandomized to tofacitinib. Pivotal study participants could enroll into the long-term extension where they received tofacitinib at 10 mg BID for 3 months, after which dosing could be 5 or 10 mg BID. RESULTS: At week 28, the proportions of patients randomized to tofacitinib 5 and 10 mg BID achieving 75% or greater reduction in Psoriasis Area and Severity Index score from baseline were 55.6% and 68.8%, and achieving Physician Global Assessment of clear or almost clear were 54.7% and 65.9%. Efficacy was maintained in most patients through 24 months. Serious adverse events and discontinuations because of adverse events were reported in less than 11% of patients over 33 months of tofacitinib exposure. LIMITATIONS: There was no dose comparison beyond week 52. CONCLUSIONS: Oral tofacitinib demonstrated sustained efficacy in patients with psoriasis through 2 years, with 10 mg BID providing greater efficacy than 5 mg BID. No unexpected safety findings were observed.

Hereditary Angioedema in Swedish Adults: Report From the National Cohort.

Hereditary angioedema (HAE) is rare, disabling and sometimes life-threatening. The aim of this study is to describe its prevalence, symptomatology and treatment in Sweden. A total of 146 patients were identified; 110 adults and 36 children with HAE type I (n = 136) or II (n = 10), giving a minimal HAE prevalence of 1.54/100,000. All patients received a written questionnaire followed by a structured telephone interview. This report focuses on the 102 adults who responded. Females reported 19 attacks in the previous year vs. 9 for males (p < 0.01), and females reported 10 days of sick leave vs. 4 days for males (p < 0.05). For all treated acute attacks, plasma-derived C1-inhibitor concentrate (pdC1INH) (used in 27% of patients) had a good effect. For maintenance treatment, 43% used attenuated androgens and 8% used pdC1INH, which reduced their attack rate by more than 50%. In conclusion, the minimal HAE prevalence in Sweden was 1.54/100,000. HAE affected females more severely. Attenuated androgens and pdC1INH had a good effect on preventing attacks.

Impact of Depression on Risk of Myocardial Infarction, Stroke and Cardiovascular Death in Patients with Psoriasis: A Danish Nationwide Study.

Psoriasis is associated with depression, myocardial infarction (MI) and stroke. Patients with depression have increased cardiovascular risk. However, the link between psoriasis, depression and cardiovascular disease is unclear. This link was investigated in a nationwide Danish cohort of patients with psoriasis (n = 29,406). Incidence rates were calculated, and incidence rate ratios (IRRs) adjusted for age, gender, socio-economic status, medication and comorbidity were estimated by Poisson regression models. Risk of MI (IRR 1.57, 95% confidence interval (95% CI) 1.07-2.29), stroke (IRR 1.95, 95% CI 1.43-2.66), and cardiovascular death (IRR 2.24, 95% CI 1.53-3.26) were increased significantly during acute depression, and risk of stroke (IRR 1.51, 95% CI 1.19-1.90) was increased significantly in chronic depression. During remission from depression, only the risk of stroke was increased. In conclusion, in patients with psoriasis, depression is associated with increased risk of MI, stroke and cardiovascular death, especially during acute depression.