Integrating Biologic Agents into Management of Moderate-to-Severe Psoriasis: A Consensus of the Canadian Psoriasis Expert Panel

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.5Objective 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.

---

SommaireAntècèdents Près de 2 % de la population mondiale est atteinte de psoriasis, dont un million de personnes au Canada.1,2 Le psoriasis peut varier de bénin à grave. Cette affection entraîne arfois une morbidité accrue et une détresse psychologique en plus d’avoir un impact négatif profond’sur la qualité de vie du patient.3,4 Bien que les traitements disponibles réduisent I’étendue et la gravité de la maladie et améliorent la qualité de vie,3 les rapports ont dénoté une préférence pour les traitements plus agressifs et une insatisfaction à I’égard de I’efficacite des options de traitement actuelles.5Objectif Un panel d’experts canadiens, formé de dermatologues, s’est réuni á Toronto le 27 février 2004 en vue d’atteindre un consensus sur les besoins non comblés des patients traités au moyen des thérapies actuelles, ainsi que d’évaluer les façons d’inclure les agents biologiques et d’améliorer les algorithmes de traitement du psoriasis modéré à grave. Actuellement, les traitements recommandés sont axés sur une stratégic par étapes, débutant avec des agents topiques, suivis d’une phototherapie et enfin des agents systémiques.3,6,7 panel a évalué le positionnement approprié des agents biologiques, une fois approuvés par Santé Canada, dans le traitement du psoriasis modéré à grave.Méthodes Le panel a passé en revue les rapports disponibles et la qualite des données relativement à ces thérapies ainsi que ceux des essais cliniques randomisés.8–14 Par la suite, un consensus a été atteint au moyen de petits ateliers de travail suivis d’une discussion plénière.Résultats Le panel a déterminé que les agents biologiques étaient un important ajout aux options thérapeutiques offertes actuellement dans le traitement du psoriasis modéré à grave et a proposé un algorithme de traitement en replacement à I’algorithme par étapes actuel.Conclusion Le panel a recommandé un nouvel algorithme de traitement pour le psoriasis modéré à grave, où on considère toutes les options thérapeutiques, y compris les agents biologiques, dans leur ensemble et on tient compte des caractéristiques et des besoins specifiques de chaque patient dans le choix de I’option adéquate.

---

---

The Canadian Expert Panel meeting was supported by an educational grant from Serono Canada Inc. The opinions expressed are those of the authors and not of Serono. All participants have been involved in clinical trials involving at least one of the therapeutic agents discussed.

---

At the time of the Canadian Expert Panel meeting, biologic agents such as alefacept, efalizumab, etanercept, and infliximab were not approved in Canada for the treatment of psoriasis. Upon final submission of this article, alefacept had just received approval for the treatment of psoriasis.     

Update on the safety of itraconazole pulse therapy in onychomycosis and dermatomycoses

As the use of newer antifungal agents becomes more widespread, safety issues surrounding their use have become more important. To date, the safety profile of itraconazole has been well defined by its worldwide use in 50 million patients over the past 13 years. Data from clinical practice and clinical trials indicate that the 1-week pulse regimen of itraconazole is well tolerated and associated with a favourable safety profile. Adverse events are generally mild and transient. Furthermore, a dose increase to 400 mg in the pulse regimen has had no adverse impact on safety.     

A practical application of onychomycosis cure – combining patient,physician and regulatory body perspectives

Due to the high relapse rates and the rise of predisposing factors, the need for curing onychomycosis is paramount. To effectively address onychomycosis, the definition of cure used in a clinical setting should be agreed upon and applied homogeneously across therapies (e.g. oral, topical and laser treatments). In order to determine what is or what should be used to define cure in a clinical setting, a literature search was conducted to identify methods used to evaluate treatment success. The limitations, strengths, prevalence and utility of each outcome measure were investigated. Seven ways to measure treatment success were identified; mycological cure, patient/investigator assessments, complete cure, quality of life instruments, severity indexes, clinical cure and temporary clearance. Despite its shortcomings, mycological cure is the most objective and consistent outcome measure used across onychomycosis studies. It is suggested that diagnostic goals of onychomycosis should be used to define cure in a clinical setting. Modifications to outcome measures such as incorporating molecular‐based techniques could be a future avenue to explore.     

Aneurysmal bone cyst arising in fibrous dysplasia during pregnancy

A case of two secondary aneurysmal bone cysts arising in fibrous dysplasia during pregnancy is reported. Marked radiographic changes were seen in one lesion over a 3-week period. The development of these cysts during pregnancy strongly suggests that the hemodynamic and/or hormonal changes of pregnancy were responsible for their formation.     

Utilization of health care resources by obese Canadians

BACKGROUND: The prevalence of obesity in Canada has been increasing in recent years. Using data from the National Population Health Survey (NPHS), the authors determined the prevalence of obesity among Canadians, the associated comorbidities and the patterns of resource utilization by obese people. METHODS: The NPHS, a cross-sectional survey conducted in 1994, was administered to 17,626 Canadians 12 years of age or older who were not long-term residents of hospitals or long-term care facilities and were not residing on First Nations reserves or Canadian Armed Forces bases, or in the Yukon and Northwest Territories. For the authors' analysis, the study population consisted of 12,318 Canadians aged 20-64 years who were not pregnant and for whom the body mass index (BMI) had been calculated. The prevalence of comorbidities, health status index scores, self-esteem, self-rated health, restriction of activity, health care resource utilization (physician visits, disability days, admissions to hospital and medication use) were determined for obese people (BMI of 27 or greater) and nonobese people. RESULTS: The NPHS data revealed that 35.2% of men and 25.8% of women in Canada were obese in 1994. Obese respondents were more likely than nonobese respondents to suffer from stress (adjusted odds ratio [OR] 1.20, 95% confidence interval [CI] 1.11-1.31), activity restrictions (adjusted OR 1.39, 95% CI 1.26-1.54) and a number of chronic comorbidities. Obese respondents were also more likely to consult with physicians (adjusted OR 1.32, 95% CI 1.22-1.43), be prescribed a number of medications and to require excess disability days (adjusted OR 1.22, 95% CI 1.08-1.36). INTERPRETATION: Obesity represents a substantial burden on the health of Canadians and on Canada's health care resources.     

Onychomycosis: a review

Onychomycosis is a fungal infection of the nail, causing discoloration and thickening of the affected nail plate, and is the most common nail infection worldwide. Onychomycosis was initially thought to be predominantly caused by dermatophytes; however, new research has revealed that mixed infections and those caused by non-dermatophyte moulds (NDMs) are more prevalent than previously thought, especially in warmer climates. Microscopy and fungal culture are the gold standard techniques for onychomycosis diagnosis, but high false-negative rates have pushed for more accurate methods, such as histology and PCR. As NDMs are skin and laboratory contaminants, their presence as an infectious agent requires multiple confirmations and repeated sampling. There are several treatment options available, including oral antifungals, topicals and devices. Oral antifungals have higher cure rates and shorter treatment periods than topical treatments, but have adverse side effects such as hepatotoxicity and drug interactions. Terbinafine, itraconazole and fluconazole are most commonly used, with new oral antifungals such as fosravuconazole being evaluated. Topical treatments, such as efinaconazole, tavaborole, ciclopirox and amorolfine have less serious side effects, but also have generally lower cure rates and much longer treatment regimens. New topical formulations are being investigated as faster-acting alternatives to the currently available topical treatments. Devices such as lasers have shown promise in improving the cosmetic appearance of the nail, but due to a high variation of study methods and definitions of cure, their effectiveness for onychomycosis has yet to be sufficiently proven. Recurrence rates for onychomycosis are high; once infected, patients should seek medical treatment as soon as possible and sanitize their shoes and socks. Prophylactic application of topicals and avoiding walking barefoot in public places may help prevent recurrence.     

Increased prevalence of familial autoimmunity in simplex and multiplex families with juvenile rheumatoid arthritis

OBJECTIVE: To determine if the prevalence of autoimmunity among relatives of patients with juvenile rheumatoid arthritis (JRA) is greater than that among relatives of healthy volunteer control subjects. METHODS: Interviews were used to obtain histories of the following disorders among living first- and second-degree relatives of 110 patients and 45 controls: alopecia areata, ankylosing spondylitis, dermatomyositis, Graves' disease, Hashimoto thyroiditis, insulin-dependent diabetes mellitus, inflammatory bowel disease, iritis, JRA, multiple sclerosis, psoriasis, RA, systemic lupus erythematosus, and vitiligo. Chi-squares, odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated. Families of 23 JRA affected sibpairs were interviewed subsequently. RESULTS: There were no significant differences between patients and controls with regard to age, sex, ethnicity, or family size. Patients had 1,228 relatives and controls had 496 relatives. Of all the relatives of the patients, 155 had at least 1 autoimmune disorder, compared with 20 relatives of the controls (12.6% versus 4.0%; OR 3.4 [95% CI 2.1-5.7], P < 0.000001). The prevalence of autoimmunity was increased in first-degree and in second-degree relatives of patients (16.1% and 10.6%, respectively). The prevalence of Hashimoto thyroiditis was significantly higher in the relatives of patients (OR 3.5 [95% CI 1.6-7.9], P = 0.0008). The prevalences of other disorders were not significantly different. JRA affected sibpair families had an increased prevalence of autoimmunity (15.0%). A history of arthritis was found significantly more frequently in the JRA affected sibpair families, but not in the simplex families. CONCLUSION: These data demonstrate that the prevalence of autoimmunity is significantly higher among first- and second-degree relatives of JRA patients. This suggests that clinically different autoimmune phenotypes may share common susceptibility genes, which may act as risk factors for autoimmunity.