Treatment of Severe Alopecia Areata: Combination Therapy Using Systemic Cyclosporine A with Low Dose Corticosteroids

BackgroundCombination therapy using cyclosporine A (CsA) together with low-dose corticosteroids has adequate efficacy with little toxicity for the treatment of severe alopecia areata (AA).ObjectiveWe wanted to evaluate the clinical efficacy of combination therapy using CsA with low-dose corticosteroid for the treatment of severe AA and we also wanted to determine the safe therapeutic concentration of CsA in the peripheral blood.MethodsWe treated 34 cases of severe AA with combination therapy for 24 weeks and we evaluated the efficacy at 12 and 24 weeks. We monitored the peripheral blood concentration of CsA to determine the therapeutic range of CsA that has the fewest side effects.ResultsOf the patients, 77.4% (n=24) and 22.6% (n=10) were classified in the responder and poor-responder groups, respectively. The mean trough concentration of CsA was 95.1 and 101.2 ng/ml in the responder and poor-responder groups, respectively. For the patients with side effects associated with CsA, the mean CsA concentration was 195.8 ng/ml.ConclusionWe found that combination therapy with systemic CsA and low-dose corticosteroids effectively treats severe AA and this therapy results in a safe, therapeutic concentration of CsA in the peripheral blood.     

伊那西普治疗银屑病的十年回顾

伊那西普是新一代的生物制剂,为近年来自身免疫性疾病领域的热门治疗药物。这些药物大多抑制在慢性炎症过程中起关键作用的肿瘤坏死因子。本文介绍了伊那西普治疗银屑病的临床疗效和作用机制,重点总结近十年来伊那西普的长期疗效和不良反应。     

Real-World Experience with Etanercept Therapy and the Switching Pattern among Korean Patients with Psoriasis after Withdrawal of Etanercept

BackgroundThe efficacy and safety of etanercept in the treatment of psoriasis has been proven, and the drug was approved for the treatment of moderate to severe psoriasis. However, there have been few studies that have presented real-world data focused on concomitant treatment during etanercept treatment, and the switching pattern after discontinuation of etanercept.ObjectiveTo reveal the real-world treatment pattern of etanercept-based psoriasis treatment and to investigate the switching pattern after withdrawal of etanercept.MethodsWe enrolled 66 patients with psoriasis who were treated with etanercept. We collected data regarding the demographic characteristics of the patients, etanercept treatment schedules, and other treatments administered during the etanercept treatment period. We also investigated the treatment pattern after the discontinuation of etanercept with emphasis on the drug-free interval and the administered treatment modalities.ResultsThe mean treatment duration was 22.7±26.1 months and the mean number of etanercept injections was 21.5±27.9. Thirty-six patients were administered concomitant systemic medication or phototherapy. After discontinuation of etanercept, 54 patients were followed up and 34 of these patients were administered other systemic medication or phototherapy; phototherapy and cyclosporine was the most commonly administered treatment modality and 27.4% of treatments used biologics.ConclusionThe treatment schedule for etanercept was modified according to the severity of psoriasis and concomitant treatment was administered to improve the effectiveness of treatment in the patients enrolled in the study. We also found that most patients required other treatment modalities to control psoriasis during the period of etanercept treatment.     

Topical Anthralin Therapy for Refractory Nail Psoriasis

The nail is commonly involved in psoriasis; however, very few therapies are satisfactory. In this study, we treated for 20 cases of psoriasis vulgaris with nail involvement with topical anthralin therapy. An ointment of 0.4–2.0% anthralin in petrolatum was applied to the affected nail bed once a day and washed away with water after 30 minutes. Then, 10% triethanolamine cream was applied to prevent undesired pigmentation. Within five months of therapy, twelve out of twenty psoriatic patients (60%) showed moderate and obvious improvement, four patients (20%) showed no response to this regimen. Onycholysis and pachyonychia both responded clinically, and the number of pitting was markedly decreased in some cases. The main side effect of anthralin therapy was reversible pigmentation of the nail plate. Topical anthralin therapy is effective for nail psoriasis and considered to be a useful treatment for refractory nail psoriasis.     

Nodular Vasculitis That Developed during Etanercept (Enbrel) Treatment in a Patient with Psoriasis

Nodular vasculitis was introduced by Montgomery for cases of erythema induratum-like lesions that were not associated with tuberculosis. Nodular vasculitis has been associated with both nontuberculous infections and noninfectious conditions. However, there has been no report on the development of nodular vasculitis during tumor necrosis factor-α inhibitor treatment. A 28-year-old man visited our clinic for the treatment of severe psoriasis with a 20-year history. Subcutaneous injection of etanercept (25 mg, twice weekly) was started. One year later, erythematous nodules developed on his lower leg. A skin biopsy showed lobular panniculitis with extensive necrosis and vasculitis. To exclude latent tuberculosis, an assay specific for Mycobacterium tuberculosis antigens was performed, with a negative result. After stopping etanercept under the diagnosis of nodular vasculitis associated with etanercept, the lesions gradually disappeared, leaving depressed scars in 3 months. There has been no recurrence after 6 months of follow-up.     

Combination Therapy with Low-Dose Etretinate and Eicosapentaenoic Acid for Psoriasis Vulgaris

A randomized open study was undertaken to compare the therapeutic effects between low-dose etretinate alone and low-dose etretinate combined with eicosapentaenoic acid in 40 patients with chronic, stable psoriasis vulgaris. Better and more rapid improvement was obtained with the combination therapy for 12 weeks than with low-dose etretinate monotherapy. Eicosapentaenoic acid was safe, and adverse reactions due to low-dose etretinate were mild or tolerable. The combination regimen, therefore, has a satisfactory effect on psoriasis without marked adverse reactions.     

Comparison of High-Dose Corticosteroid Pulse Therapy and Combination Therapy Using Oral Cyclosporine with Low-Dose Corticosteroid in Severe Alopecia Areata

BackgroundSevere alopecia areata (AA) is resistant to conventional treatment. Although systemic oral corticosteroids are an effective treatment for patients with severe AA, those drugs have many adverse effects. Corticosteroid pulse therapy has been introduced to increase therapeutic effects and reduce adverse effects. However, the treatment modality in severe AA is still controversial.ObjectiveTo evaluate the effectiveness of corticosteroid pulse therapy in patients with severe AA compared with treatment with oral cyclosporine with corticosteroid.MethodsA total of 82 patients with severe AA were treated with corticosteroid pulse therapy, and 60 patients were treated with oral cyclosporine with corticosteroid. Both groups were retrospectively evaluated for therapeutic efficacy according to AA type and disease duration.ResultsIn 82 patients treated with corticosteroid pulse therapy, 53 (64.6%) were good responders (>50% hair regrowth). Patients with the plurifocal (PF) type of AA and those with a short disease duration (≤3 months) showed better responses. In 60 patients treated with oral cyclosporine with corticosteroid, 30 (50.0%) patients showed a good response. The AA type or disease duration, however, did not significantly affect the response to treatment.ConclusionCorticosteroid pulse therapy may be a better treatment option than combination therapy in severe AA patients with the PF type.     

卡泊三醇与氯氟舒松联合外用治疗寻常型银屑病

目的 观察卡泊三醇与氯氟舒松联合分用组，氯氟舒松组及卡泊三醇单用组外用治疗寻常型银屑病的疗效与安全性。方法 患者随机分入三个治疗组，对治疗1，4周后银屑病区严重度指数(PASI)之平均百分变化率进行比较。结果 通过比较显示卡泊三醇与氯氟舒松联合分用组治疗1，4周后的PASI平均百分变化率(PASI改善率)显著高于氯氟舒松组及卡泊三醇单用组，且副反应少于单纯卡泊三醇组。结论 卡泊三醇与氯氟舒松联合外用治疗寻常型银屑病优于卡泊三醇或氯氟舒松单用疗法。     

Combination Therapy with Cyclosporine and Psoralen Plus Ultraviolet A in the Patients with Severe Alopecia Areata: A Retrospective Study with a Self-Controlled Design

Background

Alopecia areata (AA) is believed to be an organ-specific autoimmune disease in which a mononuclear cell infiltrate develops in and around anagen hair follicles. There is no definitive therapy for AA.

Objective

We sought to determine whether the combination therapy of cyclosporine and psoralen plus ultraviolet A (PUVA) could be an effective treatment for severe AA.

Methods

A total of 41 patients with severe AA were treated with oral cyclosporine and topical PUVA. Cyclosporine was given at an initial daily dose of 200 mg for adult and 100 mg for children for periods of up to 16 weeks. Eight-methoxypsoralen (Methoxsalen) was applied topically 20 minutes prior to ultraviolet A (UVA) exposure, and the patients were irradiated with UVA twice a week for 16 weeks.

Results

Of the total 41 patients, 2 (7.3%) patients were lost to follow-up, and 1 (2.4%) patient discontinued the treatment due to abdominal discomfort. Six (14.6%) patients were treated for less than 12 weeks. Of remaining 32 patients, 3 (9.4%) showed excellent response, 3 (9.4%) showed good response, 12 (37.5%) showed fair response, and 14 (43.7%) showed poor response.

Conclusion

Although limited by its uncontrolled character, this study shows that the combination therapy with cyclosporine and PUVA may be an additional choice for severe and recalcitrant AA.     

43例泛发性脓疱性银屑病临床分析及治疗

目的 探讨泛发性脓疱性银屑病(GPP)的临床特征及中西医结合的治疗方法。方法 总结分析1993～2003年我科收治的43例GPP病例。结果 GPP的重要诱因为皮质类固醇及免疫抑制剂的骤然撤减，GPP存在继发感染。中西医结合治疗有效率最高可达95％。结论 中西医结合治疗泛发性脓疱性银屑病疗效满意，可避免使用皮质类固醇。     

UVA1光疗联合卡泊三醇软膏治疗甲银屑病的临床疗效观察

目的探讨UVA1光疗联合卡泊三醇软膏治疗甲银屑病的临床疗效,进而为甲银屑病患者的治疗提供临床依据。方法将收集的60例寻常型银屑病甲损害的患者随机分为2组,均给予卡泊三醇软膏2次/d,联合治疗组予以UVA1照射(2次/周)治疗,2组治疗方案疗程均为6个月;在治疗前及治疗后,对患者进行银屑病甲严重程度指数(NAPSI)。结果 60例寻常型银屑病甲损害患者中,平均年龄(50.57±16.24)岁,2组在年龄、性别、病程比较差异无统计学意义(P0.05);2组患者病甲治疗前NAPSI评分:联合治疗组:27.07±10.86,卡泊三醇软膏组:25.93±10.73,2组比较差异无统计学意义(t=0.449,P0.05);治疗后2组NAPSI评分分别为:联合治疗组:12.67±7.60,卡泊三醇软膏组:18.10±8.93,NAPSI评分差异有统计学意义(P0.05);治疗后联合治疗组临床痊愈10例,痊愈率33.33%,有效率56.67%,卡泊三醇软膏组临床痊愈0例,痊愈率0%,有效率13.33%,2组有效率的比较有统计学意义(P0.01)。结论UVA1联合卡泊三醇软膏治疗甲银屑病的疗效优于单纯使用卡泊三醇软膏。     

达力士封包疗法治疗银屑病疗效观察

目的探索达力士软膏封包疗法和常规外用疗法的疗效和安全性。方法用左右肢体对照的方法对55例慢性斑块状银屑病患者采用达力士软膏1次/d封包疗法和2次/d常规外用治疗8周;在治疗后2,4,6,8周根据PASI评估疗效。结果在治疗2,4,6,8周时达力士组PASI评分下降值明显高于常规外用法(t分别=1.7485,2.9561,4.3547,1.88942;P<0.05),达士力组治疗4,6,8周治愈率分别达到26%,58.6%,74%;与常规疗法相比疗效差异显著(χ2=6.45,5.28,5.58,P=0.011,0.021,0.018),达力士组和常规疗法局部刺激发生率分别为15.2%和8.6%,两组疗法都未出现系统不良反应。结论达力士1次/d封包疗法治疗银屑病高效、安全、经济、快速。     

A Comparative Study of Oral Cyclosporine and Betamethasone Minipulse Therapy in the Treatment of Alopecia Areata

BackgroundVarious systemic agents have been assessed for the treatment of alopecia areata (AA); however, there is a paucity of comparative studies.ObjectiveTo assess and compare cyclosporine and betamethasone minipulse therapy as treatments for AA with regard to effectiveness and safety.MethodsData were collected from 88 patients who received at least 3 months of oral cyclosporine (n=51) or betamethasone minipulse therapy (n=37) for AA. Patients with ≥50% of terminal hair regrowth in the alopecic area were considered responders.ResultsThe responder of the cyclosporine group was 54.9% and that of the betamethasone minipulse group was 37.8%. In the cyclosporine group, patients with mild AA were found to respond better to the treatment. Based on the patient self-assessments, 70.6% of patients in the cyclosporine group and 43.2% of patients in the betamethasone minipulse group rated their hair regrowth as excellent or good. Side effects were less frequent in the cyclosporine group.ConclusionOral cyclosporine appeared to be superior to betamethasone minipulse therapy in terms of treatment effectiveness and safety.     

Clinical,Quality of Life,Patient Adherence,and Safety Outcomes of Short-Course (12 Weeks) Treatment with Cyclosporine in Patients with Severe Psoriasis (the Practice Study)

Background

Apart from clinical outcomes, the "real-world" outcomes of intermittent short-course cyclosporine treatment remain poorly documented.

Objective

To evaluate various outcomes of short-course cyclosporine treatment for severe psoriasis; and to describe dermatologists'' use of the Rule of Tens.

Methods

A 12-week pharmacoepidemiological study; 112 evaluable patients recruited by 43 dermatologists.

Results

The mean initial cyclosporine dose was 2.88±0.74 mg/kg/day. At 12 weeks, 64.3% of patients were continued beyond the study period at mean dose of 2.51±0.91 mg/kg/day. Percent body surface affected, Psoriasis Area Severity Index score, and patient and physician rating of psoriasis severity decreased significantly, while quality of life (QoL) improved significantly. Median patient satisfaction at 12 weeks was 85 (0~100 scale). Patient-reported non-adherence was 43.9% and 56.1%, respectively at both the time points (p=0.18). In modeling on logarithmized outcomes variables, living along was consistently the single most important (negative) determinant of therapeutic and patient outcomes. Safety and tolerance parameters were similar to the ones reported in the literature. Only 7.3% of physicians correctly identified the measures included in the Rule of Tens and the Rule''s criterion for inferring severe psoriasis.

Conclusion

With adequate monitoring and patient adherence, cyclosporine treatment reduces the severity of severe psoriasis, improves QoL, and is appropriately tolerated; leading to high patient satisfaction. Social support is a key determinant of therapeutic and patient outcomes and patients living along may require clinical attention. The relevance of the Rule of Tens was not evident.     

阿维A联合润燥止痒胶囊治疗寻常性银屑病临床观察

目的探讨阿维A胶囊与润燥止痒胶囊联合治疗寻常性银屑病的疗效及安全性。方法采用随机分组试验方法将84例患者分为2组。治疗组口服阿维A胶囊联合润燥止痒胶囊,对照组单纯口服阿维A胶囊,同时2组均外用卡泊三醇。疗程均为8周。于治疗前后分别做银屑病严重程度指数(PASI)积分评测。结果①两组治疗后PASI积分均降低,治疗前后积分对比差异有统计学意义(P0.05)。②治疗组有效率为88.1%,对照组为66.7%,两组有效率差异有统计学意义(P0.05);结论阿维A联合润燥止痒胶囊治疗寻常性银屑病疗效确切,能明显减轻阿维A所致的皮肤口唇干燥及瘙痒等不良反应。     

A Clinical Trial of Hydroxyurea for Psoriasis

Over a period of one year, 24 Patients with severe psoriasis have been treated with hydroxyurea in a standard dose of 1 g. daily. Seventeen patients improvement, although improvement has generally been slow. There was one case of drug fever, and one of widespread ciarcinate erythema, but otherwise side-effects have been minimal.     

The Efficacy and Safety of Long-term Oral Cyclosporine Treatment for Patients with Atopic Dermatitis

Background

Steroids are used in conventional treatment of atopic dermatitis (AD) and they are very effective for improving the symptoms, but they also have several complications. Many studies have reported that short-term use of cyclosporine (CsA) is effective for severe AD as a substitute for steroid. However, there are very few studies on the long-term use of CsA for AD in the Korean population.

Objective

The purpose of this study was to investigate whether long-term CsA therapy is effective and safe for treating AD.

Methods

We performed a retrospective study of the patients with AD and who were treated with CsA at Kyung Hee Medical Center between January 2001 and February 2008. Among 147 patients, 61 received CsA treatment for more than 6 months. To evaluate the efficacy of CsA treatment, the objective SCORAD was checked for all 61 patients at every visit. Extensive laboratory tests were performed every two months to assess the safety of treatment.

Results

The mean duration of CsA treatment was 13.5±8.4 months and the mean initial dose of CsA was 2.7±0.9 mg/kg/day. The mean objective SCORAD values significantly decreased from 34.1±11.2 at baseline to 11.4±10.7 after 6-month of CsA treatment (p<0.05). A significant decline of the SCORAD score was observed starting from 1-month of CsA treatment. The mean duration of remission was 4.5±2.9 months. A total of 13 adverse events in 10 patients were recorded during the study period. One patient dropped out due to renal dysfunction. Elevation of peripheral blood pressure was noted in 8 patients. Three patients complained of gastrointestinal troubles, and one patient had hypertrichosis, but the problems of these 4 patients were mild and easily treated.

Conclusion

We suggest that long-term, low-dose CsA treatment is safe and effective for patients who suffer from AD.     

Disease Control for Patients with Psoriasis Receiving Continuous Versus Interrupted Therapy with Adalimumab or Etanercept: A Clinical Practice Study

Background

Studies analyzing the efficacy and safety of interrupted psoriasis therapy with biologic drugs have not reported clear benefits in routine clinical practice.

Objectives

To identify differences in the disease control of psoriasis patients undergoing continuous or interrupted therapy with adalimumab or etanercept.

Methods

This retrospective 3-year cohort study (interrupted vs. continuous therapy) involved 77 patients (47 adalimumab, 30 etanercept) who were managed under clinical practice conditions. The proportion of episodes with a Physician Global Assessment (PGA) ≥3 during the follow-up in each study cohort was the primary effectiveness endpoint. The relative risk of PGA ≥3 episodes in the interrupted therapy cohort was analyzed.

Results

Twenty-one patients receiving adalimumab were included in the interrupted therapy cohort (44.7 %), and 26 were included in the continuous therapy cohort (55.3 %). In the group of etanercept, 21 patients received continuous treatment (70.0 %), and nine patients started at least one interruption period (30.0 %). The proportion of PGA ≥3 episodes in continuous and interrupted groups were 19.2 % vs. 33.3 % for adalimumab patients (p = 0.27), and 42.9 % vs. 55.6 % in patients treated with etanercept (p = 0.52). The relative risk of PGA ≥3 episodes with interrupted therapy was 1.73 (95 % confidence interval 0.64–4.68; p = 0.27), and 1.30 (95 % confidence interval 0.60–2.79; p = 0.52) in the adalimumab and etanercept groups, respectively.

Conclusion

In routine clinical practice, interrupted therapy with adalimumab or etanercept can provide adequate disease control for a subgroup of patients with excellent response to biologic drugs.