Use of Biologic Agents in Combination with Other Therapies for the Treatment of Psoriasis

Psoriasis is a chronic inflammatory skin disorder, which is associated with a significant negative impact on a patient’s quality of life. Traditional therapies for psoriasis are often not able to meet desired treatment goals, and high-dose and/or long-term use is associated with toxicities that can result in end-organ damage. An improved understanding of the involvement of cytokines in the etiology of psoriasis has led to the development of biologic agents targeting tumor necrosis factor (TNF)-α and interleukins (ILs)-12/23. While biologic agents have improved treatment outcomes, they are not effective in all individuals with psoriasis. The combination of biologic agents with traditional therapies may provide improved therapeutic options for patients who inadequately respond to a single drug or when efficacy may be increased with supplementation of another treatment. In addition, combination therapy may reduce safety concerns and cumulative toxicity, as lower doses of individual agents may be efficacious when used together. This article reviews the current evidence available on the efficacy and safety of combining biologic agents with systemic therapies (methotrexate, cyclosporine, or retinoids) or with phototherapy, and the combination of biologic agents themselves. Guidance is provided to help physicians identify situations and the characteristics of patients who would benefit from combination therapy with a biologic agent. Finally, the potential clinical impact of biologic therapies in development (e.g., those targeting IL-17A, IL-17RA, or IL-23 alone) is analyzed.     

Historical Aspects of the Oral Use of Retinoids in Acne

A number of investigations of the effects of vitamin A deficiency in animals and man and its treatment with natural products containing vitamin A were carried out in the twenties and thirties. In 1942, a clinical study in patients with acne treated with vitamin A yielded encouraging results. Further trials in the forties and fifties, trying to confirm the beneficial effect of oral vitamin A in acne, met with equivocal success. In the sixties, all-trans retinoic acid (tretinoin) became clinically available, and its topical efficacy in acne could be demonstrated. In 1971, oral tretinoin also was shown to be active in patients with acne. Coincidentally, the efficacy of oral 13-cis retinoic acid (isotretinoin) became evident in a series of unpublished studies in Europe. Then, in 1978, a trial carried out at the NIH, Bethesda, Maryland, yielded convincing evidence that isotretinoin is a potent new drug for the treatment of severe cystic acne. In 1982, isotretinoin was registered in the United States and one year later in Europe for the treatment of severe, recalcitrant, cystic acne. Since then, many thousands of patients suffering psychologically and physically from the severity of their disease have been treated successfully with this drug. However, the main concern of physicians prescribing isotretinoin has to focus on its potentially severe side effects, particularly its teratogenicity.     

Efficacy and Safety of Etanercept in Psoriasis after Switching from Other Treatments

Background: Since targeted biologic treatments have been introduced for the treatment of plaque-type psoriasis and psoriatic arthritis, switching between different medications has become necessary in selected patients, particularly after treatment failures. Objective: To evaluate the efficacy and safety of etanercept treatment in adult patients with psoriasis after failure to respond to other previous therapies. In particular, the differences in efficacy profiles after switching from traditional (cyclosporine [ciclosporin], methotrexate, retinoids, fumaric acid esters, psoralen plus UVA therapy, corticosteroids) or biologic (infliximab, efalizumab) treatments were analyzed. Methods: The study included 124 patients affected by plaque-type psoriasis who received etanercept administered subcutaneously at a dosage of 50 mg twice weekly for 12 weeks, followed by 25 mg twice weekly for an additional 12 weeks, and 110 patients affected by psoriatic arthritis who were treated with etanercept 25 mg twice weekly in a continuous regimen, after a 12-week period of treatment with etanercept 50 mg twice weekly. Results: Efficacy results were consistent in both groups of patients (plaque-type psoriasis and psoriatic arthritis), as expressed by the percentage of patients who achieved Psoriasis Area and Severity Index (PASI) 50 and PASI 75 scores. Among psoriatic arthritis patients, the mean pain Visual Analog Scale (VAS) score showed a substantial reduction during the treatment course, from 67.2 at week 0 to 15.8 at week 24. After 24 weeks, among patients with plaque-type psoriasis who had not previously received biologic therapies, 89.9% of patients achieved PASI 50 and 75.3% achieved PASI 75, while among patients who had received biologic therapies, 69.6% of patients achieved PASI 50 and 65.2% achieved PASI 75. In addition, 92.3% of patients with psoriatic arthritis who had not previously received biologic therapies achieved PASI 50 and 73.8% achieved PASI 75, while among patients who had received biologic therapies, 45.8% of patients achieved PASI 50 and 29.2% achieved PASI 75. Conclusions: Our study demonstrated that etanercept was more effective in those patients who had not previously received other biologic therapies than in those who had. The results of the present study indicate that etanercept may represent a valid, effective, and well tolerated therapeutic alternative even after failure to respond to traditional and other biologic therapies.     

卡泊三醇软膏联合口服中药治疗寻常性斑块状银屑病的临床疗效观察

目的 评价单纯外用卡泊三醇软膏和外用卡泊三醇软膏联合口服中药治疗对寻常性斑块状银屑病的疗效.方法 60例患者随即分成单纯外用卡泊三醇软膏组和外用卡泊三醇软膏联合口服中药组.疗程为12周.两组患者分别于治疗后进行临床疗效评估.结果 两组于第8周以后皮损PASI评分差异有统计学意义(P<0.05).治疗结束时,单纯西药组的有效率为73.3%,中西药联合组的有效率为93.3%,两组比较差异有统计学意义(P<0.05).结论 外用卡泊三醇软膏联合口服中药治疗寻常性斑块状银屑病优于单纯外用卡泊三醇软膏治疗.     

557例住院银屑病患者回顾性临床分析

目的分析银屑病患者的临床特点,为临床预防和诊治提供参考。方法对我院首次住院的557例银屑病患者进行回顾性分析。结果平均发病年龄男44岁,女40岁,男女之比为3∶1。初发年龄10~20岁332例(59.7%),初发部位为头皮290例(52.1%),复发加重因素受季节影响347例(62.3%)。寻常型530例(95.2%),关节病型15例(2.7%),红皮病型8例(1.4%),脓疱型4例(0.7%)。伴发心脑血管病71例(12.8%),系统应用某些特殊药物82例(14.7%)。结论银屑病患者男性多于女性,初发年龄以20~30岁最多见,初发部位以头皮为主,本病复发加重受季节影响明显,4种类型中男女患病率相似。预防为主、心理疏导+绿色治疗能取得较好的远期疗效。     

Insurance Coverage of Biologics for Moderate-to-Severe Psoriasis: A Retrospective,Observational 5-Year Chart Review

Background

With the variability in health insurance coverage for psoriasis systemic therapies, recent changes in coverage for biologics have yet to be evaluated.

Purpose

To determine changes in insurance coverage of biologics for moderate-to-severe psoriasis between 2009 and 2014, with a focus on insurance policies as stated in prior authorization (PA) forms, coverage denials, and time course of approval process.

Methods

A retrospective chart review was performed on patients with a diagnosis of psoriasis (International Classification of Diseases [ICD], Ninth Edition, code ICD 696.1) seen at the Department of Dermatology, Medical Faculty Associates, George Washington University between January 1, 2009 and December 31, 2014. Exclusion criteria included <9 % body surface area, loss to follow-up, lack of biologic treatment, biologic treatment via a clinical trial, and lack of health insurance. For all other patients, metrics collected included age, sex, body surface area, health insurance plan, prior therapies, prescribed biologic, PA necessity, time in days between PA submission and coverage decision, and denial justifications.

Results

Eight hundred and sixty-four patients with a diagnosis of psoriasis within the time period were identified, 114 of who met the inclusion criteria. PA requirement increased from 16 % of patients prescribed a biologic in 2009 to 75 % of patients prescribed a biologic in 2014. The mean duration in days between PA submission and coverage decision from the insurance company increased from 3.7 days in 2009 to 6.7 days in 2014. PA denial rates increased from 0 % in 2009 to 19 % in 2014. The most common reason for coverage denial was failure to attempt alternative therapies prior to requesting biologics.

Conclusion

Insurance coverage of biologics for moderate-to-severe plaque psoriasis has become increasingly regulated between 2009 and 2014. Given both the cost burden and potential benefits of these therapies, further examination of healthcare coverage and treatment accessibility is warranted for optimal patient outcomes.

     

The Use of Alefacept in the Treatment of Psoriasis

Journal of Cutaneous Medicine and Surgery -     

A Clinical Trial of Combination Therapy with Etanercept and Low Dose Cyclosporine for the Treatment of Refractory Psoriasis

Background

Over the past decade, combination therapies have become a mainstay of dermatologic care in psoriasis. Combination therapies are often more effective and safer than large dose single-agent therapies. With the emergence of new biologic therapies, dermatologists now have a wider array of tools to treat psoriasis. Although much data exists regarding cyclosporine or biologic agents alone for psoriasis, little is known about the efficacy, safety and tolerability of combination regimens.

Objective

We designed a study to evaluate the efficacy and safety of etanercept and cyclosporin combination therapy in patients with refractory psoriasis.

Methods

We administered oral cyclosporine (200 mg daily) and subcutaneous etanercept 50 mg weekly injections until symptoms improved, then maintained treatment at a reduced dose. Seven patients with refractory psoriasis were evaluated 4 weekly.

Results

All 7 patients showed rapid responses to combination therapy. Mean Psoriasis Area and Severity Index reductions following conditioning therapy (mean: 6.85 weeks) and maintenance therapy (mean: 56.5 weeks) were 94.9% and 93.2%, respectively.

Conclusion

Etanercept and low-dose cyclosporine combination therapy appears to be a safe and efficacious alternative treatment strategy for patients with refractory psoriasis. The combination induced rapid improvement in patients with refractory psoriasis and dramatically improved their quality of life. Clinical studies including larger patient cohort are required to validate the safety and efficacy of this combination therapy.     

冰黄肤乐软膏联合氯倍他索霜治疗寻常型银屑病临床观察

目的评价冰黄肤乐软膏联合氯倍他索霜治疗寻常型银屑病临床疗效。方法治疗组43例,每日外搽冰黄肤乐软膏、氯倍他索霜各1次;对照组32例单用氯倍他索霜,2次/d。治疗后第2、第3周用PASI评分法评定疗效。结果治疗后2周,治疗组治愈率为37.21%,有效率为76.74%,对照组分别为46.87%和84.44%;治疗后3周,治疗组分别为44.19%和81.34%;对照组分别为53.13%和87.50%;两组PASI评分及上述疗效指标差异无显著性(P>0.05);治疗组出现副作用2例,对照组出现6例(P<0.01)。结论冰黄肤乐软膏联合氯倍他索霜外用治疗寻常型银屑病与单用氯倍他索霜疗效相近,但副作用明显减少。     

口服阿维A联合窄谱UVB治疗掌跖脓疱病疗效观察

目的观察口服阿维A联合窄谱UVB治疗掌跖脓疱病的疗效。方法治疗组口服阿维A 10~30 mg/d,同时窄谱UVB照射患处,隔日1次;对照组窄谱UVB照射患处,隔日1次,疗程均为40天。结果两组有效率分别为85.29%和60.71%(P<0.05),治疗组疗效优于对照组。结论口服阿维A联合窄谱UVB治疗掌跖脓疱病疗效确切,不良反应少。