Evaluation of Risk of Major Adverse Cardiovascular Events With Biologic Therapy in Patients With Psoriasis.

BACKGROUND: Psoriasis is associated with increased risk of major adverse cardiovascular events (MACE). OBJECTIVES: Compare MACE risk with biologics vs topical/phototherapy use. METHODS: Psoriasis Longitudinal Assessment Registry (PSOLAR) is an international psoriasis registry of patients eligible to receive biologic/systemic treatments prospectively. MACE is defined as myocardial infarction, stroke, or cardiovascular death. Biologic cohorts, including tumor necrosis factor-alpha (TNF-α) inhibitors (ie, adalimumab, etanercept, and infliximab) and ustekinumab, combined and by class, were compared with a topical/phototherapy cohort. Incidence rates of MACE per 100-patient-years (100PY) with 95% confidence intervals (95% CI) are reported. Multivariate analyses were performed to evaluate the effect of treatment on the risk of MACE adjusting for confounders. RESULTS: Analyses included 7550 patients: 6767 in the combined biologics cohort (3949 and 2818 in the TNF-α inhibitors and ustekinumab cohorts, respectively) and 783 in the topical/phototherapy cohort. Mean duration of exposure was approximately 2.8 years (combined biologics) and 4.1 years (topical/phototherapy). A total of 52 MACE were reported; MACE incidence rates were 0.22/100PY (95% CI: 0.16, 0.30) for the combined biologics cohort (TNF-α inhibitors [0.20/100PY (0.12, 0.31)] and ustekinumab [0.24/100PY (0.15, 0.37]) and 0.34/100PY (0.17, 0.61) for the topical/phototherapy cohort. For the combined biologics (hazard ratio=0.92; 95% CI [0.426, 1.988]), TNF-α inhibitor (0.85 [0.373, 1.928]), and ustekinumab (1.03[0.440, 2.402]) cohorts, treatment was not associated with increased risk of MACE versus the topical/phototherapy cohort. CONCLUSION: Based on data accumulated to date in PSOLAR, treatment with biologics did not have an impact on the risk of MACE in patients with moderate-to-severe psoriasis.

J Drugs Dermatol. 2017;16 (10):1002-1013.

Risk of myocardial infarction in canadian patients with psoriasis: a retrospective cohort study.

BACKGROUND: Studies have shown that psoriatic patients are at increased risk for myocardial infarction (MI) and stroke. There is a lack of data on MI risk in Canadian psoriatic patients. OBJECTIVE: To compare MI risk in Canadian psoriatic patients to that in control patients. METHODS: This was a retrospective cohort study using Quebec's health insurance database (2005-2010) comparing MI risk in psoriatic patients to that in matched controls. Severe psoriasis was defined as any diagnosed psoriatic patient who used phototherapy or oral or injectable psoriasis treatments. Adjustments were made for several MI risk factors. RESULTS: There were 31,421 patients in the psoriasis population, of which 5,159 had severe psoriasis. The unadjusted MI incidence rate per 1,000 person-years was 4.88 (95% confidence interval [95% CI] 4.50-5.20), 5.58 (95% CI 5.10-6.10), and 5.32 (95% CI 4.40-6.40) for the control and mild and severe psoriasis groups, respectively. After adjustments, the hazard ratio of MI was significantly higher for psoriatic patients than for controls (1.17; 95% CI 1.04-1.31). The hazard ratio was also significantly higher than for controls in the mild psoriasis group (1.18; 95% CI 1.05-1.33) but not in the severe psoriasis group (1.16; 95% CI 0.94-1.42). CONCLUSION: The relative MI risk is higher for Canadian psoriatic patients than for controls.

Effects of the tumor necrosis factor-α antagonist adalimumab on arterial inflammation assessed by positron emission tomography in patients with psoriasis: results of a randomized controlled trial.

BACKGROUND: Psoriasis is a chronic inflammatory disease associated with increased risks of myocardial infarction and stroke. Systemic treatments for moderate to severe psoriasis can reduce skin and joint inflammation; however, their effects on vascular inflammation are unknown. METHODS AND RESULTS: This randomized, controlled trial included 30 patients with moderate to severe psoriasis and a history, or multiple risk factors, of coronary atherosclerosis. Patients were randomized (2:1) to receive either adalimumab subcutaneously for 4 months or to control nonsystemic treatment (topical therapies or phototherapy). Vascular inflammation was measured in the carotid artery and ascending aorta at baseline and week 15, by (18)F-fluorodeoxyglucose uptake on positron emission tomography. The change in target: BACKGROUND: =0.004) but not for the control group (-0.10 [95% CI, -0.32 to 0.12]; P=0.35). The difference between study arms for this primary end point did not reach statistical significance (-0.13 [95% CI, -0.01 to 0.14]; P=0.32). The change in target: BACKGROUND: =0.021) and in carotid arteries (-0.32±0.15, P=0.037) when analyzed separately (secondary end points). Changes in other positron emission tomography indices also improved significantly with adalimumab compared with controls in the ascending aorta and carotids. High-sensitivity C-reactive protein decreased by 51% at week 16 with adalimumab compared with 5% in controls (P=0·002). CONCLUSIONS: The study did not meet its primary end point because the change in target:background ratio in patients randomized to adalimumab was not different from controls. Although adalimumab may reduce vascular inflammation in patients with moderate to severe psoriasis, this effect is not large enough to be demonstrated in a study with a small sample size. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00940862.

A randomized study comparing the combination of nbUVB and etanercept to etanercept monotherapy in patients with psoriasis who do not exhibit an excellent response after 12 weeks of etanercept.

BACKGROUND: There is a lack of data on the combination of phototherapy with etanercept in patients who have not shown an excellent response to etanercept monotherapy. OBJECTIVES: To study the combination of narrow-band ultraviolet B (nbUVB) phototherapy with etanercept in patients not demonstrating an improvement of 90% in their Psoriasis Area Severity Index (PASI-90) after 12 weeks of etanercept. PATIENTS AND METHODS: Psoriatic patients not reaching PASI-90 after 12 weeks of etanercept therapy were randomized (1:1) to receive either etanercept (50 mg once a week) monotherapy or in combination with nbUVB three times weekly for periods of 4 weeks. RESULTS: Seventy-five patients were randomized. Only 21.6% of patients achieved adherence of 80% or more for nbUVB treatments. At week 24, PASI-90 was reached by 16.2% of patients in the etanercept plus nbUVB group when compared with 15.8% of patients in the etanercept monotherapy group (p = 1.000). In patients with high adherence to nbUVB, the PASI-90 at week 16 was 42.9% for etanercept with nbUVB when compared with 3.4% for etanercept monotherapy (p = 0.018). Both treatments were well tolerated. CONCLUSION: Addition of nbUVB after 12 weeks of etanercept did not significantly improve the clinical response except for a subset of patients with high adherence to nbUVB. CLINICAL TRIALS REGISTRATION NUMBER: NCT00640393.

Canadian hand dermatitis management guidelines.

BACKGROUND: Hand dermatitis (HD) is one of the most common skin conditions; however, it is not a homogeneous disease entity. The severity of HD may range from very mild cases to severe chronic forms, which may result in prolonged disability and, occasionally, refractory HD. Chronic hand dermatitis (CHD) is associated with a high health- economic burden and significant loss of quality of life. OBJECTIVE: Although numerous treatment options are available, the management of CHD is often difficult and unsatisfactory. There is a paucity of well-designed, randomized, controlled clinical trials in support of the efficacy of established treatment modalities. CONCLUSION: These guidelines cover the epidemiology, burden, quality of life, etiology, diagnosis, classification, and prevention of HD and provide guidance on management using an approach that is as evidence based as possible.

Efficacy outcomes in patients using alefacept in the AWARE study.

BACKGROUND: Alefacept has demonstrated efficacy in clinical trials of patients with chronic plaque psoriasis, either as monotherapy or combined with other treatment modalities such as phototherapy. OBJECTIVE: AWARE (Amevive Wisdom Acquired from Real-World Evidence) is a multicenter, observational, phase IV Canadian registry of psoriasis patients treated with alefacept. METHODS: Patients with chronic plaque psoriasis were treated with at least one course of alefacept, either alone or added on to their existing antipsoriatic treatment regimen. Each course of alefacept was followed by a period of at least 12 weeks off treatment. Efficacy outcomes included physicians' and patients' assessments of response at week 18, as well as change in percent body surface area (BSA) involvement with psoriasis. The time to retreatment was assessed in patients receiving a second course of alefacept during at least 60 weeks of prospective follow-up. RESULTS: The majority of patients received alefacept in combination with other antipsoriatic therapies. Physicians' and patients' assessments of response at 18 weeks showed that 42% and 41% of patients, respectively, had a "cleared to marked response" and a further 42% had a "moderate to some response." Among those patients whose psoriasis was moderately controlled or not controlled at baseline, 49 to 51% and 33 to 36%, respectively, improved to "cleared to marked response" at 18 weeks. A substantial shift in percent BSA involvement with psoriasis was observed at 18 weeks, with 55% of patients having a BSA involvement of < 10% at week 18 compared to only 20% having this level of BSA involvement at baseline. The mean time to retreatment among the 60% of patients who received a second course of alefacept was 19.3 weeks (range 2-47 weeks). CONCLUSION: A single course of alefacept therapy improved outcomes in this broad population of real-world chronic plaque psoriasis patients. STUDY LIMITATIONS: The limitations of this study include its nonrandomized, noncontrolled, noncomparative design, which allowed multiple different treatment approaches across all patients. The rating scales used in this study have not been previously validated, and ranges were assigned to baseline control and response data that are not specifically defined. Clinicians did not receive specific training in using these scales; therefore, interrater variability could not be assessed.

Patterns of combination therapy with alefacept for the treatment of psoriasis in Canada in the AWARE study.

BACKGROUND: Evidence from clinical trials supports the use of alefacept for the treatment of patients with chronic plaque psoriasis, either as monotherapy or combined with other treatment modalities. OBJECTIVE: AWARE (Amevive Wisdom Acquired from Real-World Evidence) is a multicenter, observational, phase IV Canadian registry of psoriasis patients treated with alefacept. METHODS: Patients with chronic plaque psoriasis were treated with at least one course of alefacept treatment followed by a period of at least 12 weeks off-treatment. The use of combination therapy with alefacept in a real-world population of psoriasis patients is presented here, including the types of psoriasis therapies received by patients at the time of enrolment, reasons for initiating alefacept, and discontinuation or dosage reduction of concomitant therapy. RESULTS: The majority of patients were receiving other antipsoriatic therapies at the time of enrolment into the AWARE study, most commonly topical therapy, systemic agents, or phototherapy. Most patients were receiving monotherapy prior to the initiation of alefacept. There was little change in the use of topical therapies with alefacept at 24 weeks, whereas a substantial proportion of patients were able to reduce or discontinue concomitant systemic therapies and/or phototherapy. The use of combination therapy regimens was relatively consistent across the country and by age groups, although younger patients were prescribed systemic agents more often than older patients. CONCLUSION: Alefacept is commonly added to other antipsoriatic therapies in a broad population of real-world chronic plaque psoriasis patients in Canada and may allow for dosage reduction or discontinuation of concomitant systemic agents or phototherapy.

XP-828L in the treatment of mild to moderate psoriasis: randomized, double-blind, placebo-controlled study.

BACKGROUND: XP-828L, a protein extract obtained from sweet whey, has demonstrated potential benefit for the treatment of mild to moderate psoriasis in an open-label study. OBJECTIVE: To study in a randomized, double-blind, placebo-controlled study the safety and efficacy of XP-828L in the treatment of mild to moderate psoriasis. DESIGN: XP-828L 5 g/d (group A, n=42) or placebo (group B, n=42) was given orally for 56 days followed by XP-828L 5 g/d in group A and by XP-828L 10 g/d in group B for an additional 56 days. RESULTS: Patients receiving XP-828L 5 g/d for 56 days had an improved Physician's Global Assessment (PGA) score compared with patients under placebo (p less than 0.05). Considering the data of group A only, the PGA score improved from day 1 to day 56 (p less than 0.01); the Psoriasis Area and Severity Index score improved as well, but to a lesser extent (p less than 0.05). CONCLUSION: Oral administration of 5 g/d XP-828L compared with a placebo significantly improved the PGA score of patients with mild to moderate psoriasis.

Integrating biologic agents into management of moderate-to-severe psoriasis: a consensus of the Canadian Psoriasis Expert Panel. February 27, 2004.

BACKGROUND: Approximately 2% of people worldwide have psoriasis, with as many as 1 million people with psoriasis in Canada alone.1,2 The severity of psoriasis ranges from mild to severe. It can lead to substantial morbidity and psychological stress and have a profound negative impact on patient quality of life.3,4 Although available therapies reduce therapies reduce the extent and severity of the disease and improve quality of life,3 reports have indicated a patient preference for more aggressive therapy and a dissatisfaction with the effectiveness of current treatment options.5 OBJECTIVE: A Canadian Expert Panel, comprising Canadian dermatologists, convened in Toronto on 27 February 2004 to reach a consensus on unmet needs of patients treated with current therapies and how to include the pending biologic agents in and improve the current treatment algorithm for moderate-to-severe psoriasis. Current treatment recommendations suggest a stepwise strategy starting with topical agents followed by phototherapy and then systemic agents.3,6,7 The Panel evaluated the appropriate positioning of the biologic agents, once approved by Health Canada, for the treatment of moderate-to-severe psoriasis. METHODS: The Panel reviewed available evidence and quality of these data on current therapies and from randomized, controlled clinical trials.8-14 Subsequently, consensus was achieved by small-group workshops followed by plenary discussion. RESULTS: The Panel determined that biologic agents are an important addition to therapies currently available for moderate-to-severe psoriasis and proposed an alternative treatment algorithm to the current step wise paradigm. CONCLUSION: The Panel recommended a new treatment algorithm for moderate-to-severe psoriasis whereby all appropriate treatment options, including biologic agents, are considered together and patients' specific characteristics and needs are taken into account when selecting the most appropriate treatment option.