依那西普治疗银屑病的疗效

目的 探讨重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白依那西普对中重度寻常性银屑病的疗效。方法 2008年2月至2011年12月,诊断为中重度寻常性银屑病且经治疗疗效差的患者24例,给予抗肿瘤坏死因子靶向治疗（依那西普25 mg皮下注射,每周2次,疗程3个月）,随访6个月,按银屑病面积和严重程度指数（PASI）和医师整体评估标准（PGA）对疗效进行评分。结果 经依那西普治疗24周后,24例寻常性银屑病PASI减少75%的有12例（50%）,1例无效,4例注射部位有红肿等不良反应。 结论 对于其他治疗疗效不佳的中重度寻常性银屑病患者,用抗肿瘤坏死因子治疗有效。     

Human papillomavirus in cutaneous squamous cell carcinoma and cervix of a patient with psoriasis and extensive ultraviolet radiation exposure

"High-risk" human papillomaviruses (HPVs) are associated with intraepithelial neoplasia and cancer of the uterine cervix. HPV has also been found in nonmelanoma skin cancer (NMSC), especially in squamous cell carcinomas (SCCs) of immunosuppressed patients. Recently, lesions of psoriasis have been shown to harbor HPV, and patients with psoriasis often have a history of extensive therapy with ultraviolet radiation (UVR). UVR is the major known risk factor in the occurrence of NMSC, in which HPV may be a cofactor for SCC. We report an otherwise healthy, nonimmunosuppressed patient with psoriasis who had a history of extensive exposure to UVR and experienced multiple SCCs on UV-exposed body sites. By the polymerase chain reaction method, we detected HPV in 5 of 9 SCCs. Automated sequencing showed HPV types 12 and 17. Only 1 of 3 normal skin specimens was HPV positive (HPV type 17). This positive specimen was from UV-exposed skin; one of the two HPV-negative, normal skin specimens was located on a body site not exposed to sun. In addition, HPV type 62 was found in a brush specimen of the uterine cervix. This case report suggests an association between psoriasis, HPV infection, and UVR exposure, in onset of SCC.     

The treatment of psoriasis with etanercept

Etanercept is a tumor necrosis factor alpha (TNF-alpha) inhibitor approved for the treatment of psoriasis. Etanercept is a soluble version of the tumor necrosis factor receptor (TNFR) that neutralizes the proinflammatory activity of TNF-alpha, a molecule central to the pathogenesis of psoriasis. Patients receiving etanercept continuously during both 12 and 24 weeks show a significant reduction in the signs of psoriasis. Further, higher doses of etanercept provide better efficacy. Both clinical trial and postmarketing experience with etanercept is extensive and, thus, etanercept has a well-defined safety and tolerability profile. With appropriate patient selection and follow-up, etanercept therapy has a very good benefit-to-risk ratio and represents a convenient option for patients with moderate-to-severe psoriasis.     

Terbinafine in fungal infections of the nails: a meta-analysis of randomized clinical trials

BACKGROUND: The antitumour necrosis factor (TNF) activity of etanercept has been utilized to generate an important and novel treatment for rheumatoid arthritis. TNF has also been implicated in the pathogenesis of psoriasis. OBJECTIVES: To determine whether blockade of TNF activity by etanercept may provide an additional treatment option for patients with psoriasis. METHODS: In an uncontrolled trial, etanercept was added to the treatment regimen in six patients with severe recalcitrant psoriasis (three also with psoriatic arthritis) partially resistant to other ongoing systemic agents. RESULTS: In each case, the disease activity showed marked improvement on addition of etanercept therapy. No added toxicity was found with etanercept. CONCLUSIONS: Etanercept appears to be a promising immunomodulatory agent that can be used in combination therapy for the treatment of psoriasis, and a prospective controlled trial may be warranted.     

No evidence for increased risk of cutaneous squamous cell carcinoma in patients with rheumatoid arthritis receiving etanercept for up to 5 years

OBJECTIVE: To determine the incidence of cutaneous squamous cell carcinoma (SCC) in patients with rheumatoid arthritis receiving etanercept, a tumor necrosis factor antagonist, for up to 5 years. DESIGN: An etanercept clinical trials' database and an etanercept postmarketing surveillance database were retrospectively analyzed for the incidence of SCC. SETTING: Patients enrolled in clinical trials of etanercept were from private and institutional practices. The postmarketing database comprised reports from postmarketing trials and solicited and spontaneous reports.Patients A total of 1442 patients with rheumatoid arthritis with 4257 patient-years of etanercept exposure (median exposure, 3.7 years) are included in the clinical trials' database. More than 125,000 patients with more than 250,000 patient-years of etanercept exposure are included in the etanercept postmarketing database.Interventions Most patients enrolled in clinical trials of etanercept received a dosage of 25 mg of etanercept subcutaneously twice weekly for most of the time they received etanercept therapy. RESULTS: Only 4 cases of SCC were observed in the etanercept clinical trials' database, an incidence that compares favorably with the expected incidences based on general population data from Arizona (13.1) and Minnesota (5.9). Similarly, few cases of SCC (1 per 10,000 patient-years) have been reported during postmarketing surveillance of etanercept therapy. CONCLUSION: In patients with rheumatoid arthritis, etanercept use of up to 5 years does not seem to be associated with an increase in the incidence of cutaneous SCC.     

Long-term follow-up of skin cancer in the PUVA-48 cooperative study

Five-hundred fifty-one psoriasis patients receiving therapy with psoralen plus UVA light in seven medical centers for up to 10 years were evaluated for the development of skin cancer. Basal cell carcinoma developed in 13 patients (2.4%), and squamous cell carcinoma (SCC) developed in 9 (1.6%), an incidence that is significantly elevated over that in the general population. The increase in basal cell carcinoma was found only in patients with exposure to other carcinogenic agents, whereas the increase in SCC was also seen in patients without such exposures. Cumulative UVA dosage was not correlated with the development of basal cell carcinoma, but there was a trend of increasing numbers of SCCs in patients with higher dosages. Five of 9 patients had SCCs on sites that were not sun exposed. All patients with tumors had them treated surgically, and, to date, none have recurred. This study confirms a previous report of an increase in the incidence of SCC in psoriatic patients treated with PUVA.     

Etanercept in a Patient with Severe Psoriasis and Latent Viral Hepatic Disease and Latent Tuberculosis

This case report describes the effective use of etanercept in a 63-year-old male patient with moderate to severe psoriasis and vitiligo unresponsive to local and systemic therapies. Latent tuberculosis was diagnosed at baseline and the patient was treated with isoniazid for 9 months. One month after starting isoniazid, etanercept therapy (12 weeks) for psoriasis was initiated. One month later, hepatitis B virus (HBV) markers were detected, but virological tests for active HBV were negative. Isoniazid and etanercept treatments were completed without incidence. Further clinical investigations are required to confirm the potential effects of anti-tumour necrosis factor alpha agents in such patients.     

Patient-reported outcomes of psoriasis improvement with etanercept therapy: results of a randomized phase III trial

BACKGROUND: Etanercept, a soluble tumour necrosis factor receptor, lessens the severity of psoriasis as measured by physician-reported clinical outcomes. Equally important is the patient perspective on the effect of etanercept therapy on daily life. OBJECTIVES: To assess patient-reported outcomes (PROs) in patients with psoriasis receiving etanercept therapy. METHODS: In this multinational, randomized, phase III trial, patients with psoriasis received placebo (n = 193), etanercept 50 mg per week (n = 196) or etanercept 50 mg twice weekly (n = 194) during the initial 12-week, double-blind period. Thereafter, all patients received open-label etanercept (50 mg per week). The following PROs were assessed: Dermatology Life Quality Index (DLQI), Short Form-36 Health Survey (SF-36), patient rating of pruritus, and patient global assessment of psoriasis. RESULTS: At week 12, DLQI total score improved by 65-70% in patients receiving etanercept compared with 6% in patients receiving placebo (P < 0.0001), and improvement in DLQI was clinically meaningful (> or = 5-point improvement or 0 score) for 72-77% of patients receiving etanercept therapy. All DLQI and SF-36 subscales and the SF-36 physical and mental component summary scores demonstrated significantly greater improvement with etanercept therapy than with placebo, illustrating that etanercept benefits patients with psoriasis across multiple domains that contribute to health-related quality of life. With etanercept therapy, distributions of patient ratings of pruritus and global assessment of disease shifted from moderate to severe (baseline) to minimal to good (week 12). Etanercept-induced benefits of PROs were maintained for patients who reduced their dose after 12 weeks. CONCLUSIONS: Etanercept therapy improves PROs in patients with psoriasis and makes a meaningful difference to their lives. These results support the efficacy profile of physician-reported clinical measures while providing a more complete understanding of the benefits experienced by patients with psoriasis treated with etanercept.     

Combining systemic retinoids with biologic agents for moderate to severe psoriasis

Background Moderate to severe psoriasis, which is defined as psoriasis affecting more than 20% of the body surface area, often requires a combination of therapies to achieve remission. Although numerous data exist regarding the use of acitretin and biologic agent therapy alone for psoriasis, little is known about the efficacy, safety, and tolerability of acitretin combined with biologic agents. Methods Fifteen patients with psoriasis treated with concomitant acitretin and a biologic agent were identified, and their charts were reviewed for response to therapy, additional therapy necessary for disease management, side‐effects, and laboratory abnormalities whilst on combination therapy. The Institutional Review Board did not require approval for this chart review. Results Twenty‐nine per cent of patients showed clearance of psoriasis, 43% of patients showed an improvement of 90%, 14% showed an improvement of 75%, and 7.1% showed no change. During treatment with acitretin and biologic agent, five patients required no adjunctive treatment. Three patients were able to stop narrow‐band ultraviolet‐B (UV‐B) therapy after an average of 2.33 months of combination therapy. Only one patient continued to require phototherapy (UV‐B) in addition to the biologic agent. Three patients developed squamous cell carcinoma (SCC) whilst on combination therapy, but all patients had a previous history of SCC. One patient developed non‐Hodgkin's lymphoma after 3 years of etanercept and acitretin, and the etanercept was discontinued. Conclusions Acitretin combined with biologic agents offers a promising method of managing refractory psoriasis. More research is needed to determine the long‐term safety and efficacy of this combination.     

Oral retinoid use reduces cutaneous squamous cell carcinoma risk in patients with psoriasis treated with psoralen-UVA: a nested cohort study

BACKGROUND: Small open studies of patients at high risk for squamous cell carcinoma (SCC) of the skin suggest that oral retinoid use reduces the risk of these tumors. Among patients at lower risk, randomized trials of low doses of retinoids did not demonstrate significant chemopreventive effects. Patients with psoriasis treated with oral psoralen-UVA have a high risk of SCC development. Oral retinoids are used to treat psoriasis. We performed a nested cohort study to assess whether oral retinoids reduce skin cancer risk among patients with psoriasis exposed to psoralen-UVA. METHODS: From 1985 to 2000, 135 patients (11.3% of surviving patients in our cohort) used retinoids for at least 26 weeks in 1 year or more. For these 135 patients, we compared each person's SCC and basal cell carcinoma incidence during years of substantial oral retinoid use and other years. We used Poisson regression models to adjust for potential confounders. RESULTS: In a paired analysis, which compared each patient's own tumor experience while using and not using retinoids, retinoid use was associated with a 30% reduction in SCC incidence (196 SCCs/1000 and 302 SCCs/1000 years of use and no use, respectively; P =.002). After adjusting for other factors associated with SCC risk, the incidence of SCC was significantly decreased during years of substantial retinoid use (incidence rate ratio = 0.79; 95% confidence interval = 0.65, 0.95). Oral retinoid use and basal cell carcinoma incidence were not significantly associated. CONCLUSION: In patients with psoriasis treated with psoralen-UVA, systemic retinoid use reduced SCC risk but did not significantly alter basal cell carcinoma incidence.     

Adalimumab for psoriasis patients who are non-responders to etanercept: open-label prospective evaluation

Background  Targeted biologic therapies have made a significant impact on the treatment for moderate to severe psoriasis. In the United Kingdom, the National Institute for Health and Clinical Excellence recommends etanercept, a human recombinant tumour necrosis factor (TNF) receptor fusion protein, for moderate to severe psoriasis patients who have failed conventional therapies. There is, however, no data available on the role of other TNF antagonists for patients who have failed etanercept. Adalimumab, a fully human, anti-TNF monoclonal antibody, is approved for treatment of moderate to severe psoriasis.
Objectives  To assess the efficacy and safety of adalimumab (40 mg weekly) in psoriasis patients who were non-responders to high-dosage etanercept (50 mg twice weekly).
Methods  All patients attending a tertiary referral service for severe psoriasis who were non-responders to high-dosage etanercept [i.e. failed to achieve ≥ 50% improvement in Psoriasis Area and Severity Index (PASI 50) after 12 weeks of treatment] were considered for open-label adalimumab therapy for 12 weeks. Details on clinical course, PASI, Dermatology Life Quality Index (DLQI) and adverse events were recorded at baseline and weeks 2, 4, 8, and 12.
Results  Four of five patients in this study had reached at least PASI 50 by week 12. Of these, two patients achieved a 75% improvement in PASI (PASI 75). No serious adverse events were reported.
Conclusions  Initial data from this open-label prospective evaluation suggests that weekly adalimumab therapy is an effective treatment for patients with severe psoriasis who had failed to respond to at least 3 months of high-dosage etanercept.     

Cost-effectiveness analysis of TNF-α blockers for the treatment of chronic plaque psoriasis in the perspective of the Italian health-care system

The cost-effectiveness of biological treatments for psoriasis is not well determined and may vary from country to country. The objectives of this study was to perform a cost-effectiveness analysis of infliximab compared with other anti-tumor necrosis factor-α agents for the treatment of psoriasis in Italy. The incremental cost-effectiveness ratio per patients achieving at least 75% improvement in the psoriasis area and severity index assessed over 24- and 48–50-week periods was calculated. Efficacy data were drawn from randomized controlled trials when available or from open label studies. Considering patients achieving psoriasis area and severity index at week 24 and 48–50, infliximab was dominant (more effective and less costly) over etanercept given at 50 mg twice weekly. In contrast, infliximab was not dominant over etanercept at other dosages or over adalimumab. When considering the impact of therapy on quality of life at Week 12 using the Dermatology Life Quality Index equal to zero, infliximab resulted more effective and less costly than etanercept. Therefore, infliximab seems to be cost-effective in the therapy of psoriasis. Further cost-efficacy evaluations based on head-to-head trials are necessary to address health economic considerations.     

A randomized, ‘head‐to‐head’ pilot study comparing the effects of etanercept monotherapy vs. etanercept and narrowband ultraviolet B (NB‐UVB) phototherapy in obese psoriasis patients

Background Etanercept is a tumour necrosis factor‐alpha antagonist used for the treatment of moderate‐to‐severe psoriasis. Current opinion suggests that etanercept may have reduced efficacy in obese patients. Narrowband ultraviolet B (NB‐UVB) phototherapy is unaffected by body weight and the addition of NB‐UVB to etanercept therapy may supplement the efficacy of etanercept in these patients. Objective To evaluate the efficacy and safety of NB‐UVB phototherapy when administered in conjunction with 50 mg of etanercept once weekly in the treatment of obese patients with moderate‐to‐severe plaque psoriasis. Methods Thirty psoriasis patients with a body mass index (BMI) greater than 30 were enrolled into this randomized, ‘head‐to‐head’ comparison study. All subjects received 50 mg of etanercept twice weekly for 12 weeks and then randomized to receive either etanercept monotherapy or combination etanercept and NB‐UVB three times weekly for an additional 12 weeks. Treatment response was evaluated using Psoriasis Area and Severity Index (PASI), body surface area (BSA) and Physician’s Global Assessment (PGA) scores. Results Twenty‐five subjects completed the study. At 12 weeks, 48% of all patients achieved PASI 75. By Week 24, 62.5% of all patients achieved PASI 75. Patients in the etanercept monotherapy and combination etanercept and NB‐UVB phototherapy arms had similar rates of achieving PASI 75 (46.7% vs. 53.3% of each group, respectively). Conclusion Combination etanercept and NB‐UVB has similar efficacy to etanercept monotherapy in obese patients. This result indicates that even in the setting of obesity, the majority of patients respond well to etanercept, with or without NB‐UVB.     

Etanercept

Etanercept (Enbrel), a tumor necrosis factor-alpha antagonist produced by recombinant technology, is approved for use in the US as subcutaneous monotherapy in adults with moderate-to-severe psoriasis who are candidates for systemic therapy or phototherapy. The drug is also indicated in patients with psoriatic arthritis, in whom it may be used in combination with methotrexate. In well designed trials in patients with moderate-to-severe psoriasis, short-term etanercept therapy (typically 25 or 50 mg twice weekly) significantly increased the proportion of patients achieving a 75% reduction in the Psoriasis Area and Severity Index score compared with placebo. Similarly, in well designed trials in patients with psoriatic arthritis, treatment with short-term etanercept 25 mg twice weekly, alone or in combination with methotrexate, improved clinical features of the disease, while radiographic progression of joint damage appeared to be significantly slowed in a nonblind 1-year extension. Short-term etanercept therapy was well tolerated in patients with psoriasis or psoriatic arthritis. Etanercept is thus a valuable new option for the treatment of patients with chronic moderate-to-severe plaque psoriasis (who are candidates for systemic therapy or phototherapy or have failed other systemic therapies) or with psoriatic arthritis.     

A Case of Tumor Necrosis Factor-�� Inhibitors-induced Pustular Psoriasis

Anti-tumor necrosis factor (TNF)-α agents promise better disease control for the treatment of ankylosing spondylitis resistant to classical disease-modifying treatments. Etanercept, a recombinant human TNF receptor fusion protein, is used to treat a variety of TNF-α-mediated diseases by inhibiting the biological activity of TNF-α. We experienced a case of pustular psoriasis in a 32-year-old man during anti-TNF-α therapy with etanercept. He had a history of ankylosing spondylitis for 2 years. Two years after treatment of etanercept, erythematous pustules developed on his palms and soles. He had no previous history of pustular psoriasis. The skin lesion improved as the etanercept therapy was stopped, but pustular skin eruption recurred as adalimumab, a different TNF-α inhibitor, was administered to manage his ankylosing spondylitis. Several TNF-α inhibitors have different molecular structures, but these inhibitors might have a similar potency to induce pustular psoriasis from this case.     

Interstitial granulomatous dermatitis associated with the use of tumor necrosis factor alpha inhibitors

BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) has been implicated in the pathogenesis of numerous inflammatory and autoimmune disorders. Accordingly, TNF-alpha inhibitors, such as thalidomide, infliximab (Remicade), adalimumab (Humira), and etanercept (Enbrel), have been used with success in the treatment of autoimmune disorders, including psoriasis, rheumatoid arthritis, inflammatory bowel diseases, and lymphoproliferative disorders. Although anti-TNF-alpha therapy is safe and well tolerated, various adverse cutaneous reactions have been reported. OBSERVATIONS: We encountered 5 patients who developed erythematous annular plaques on the trunk and extremities while receiving 4 different medications with inhibitory activity against TNF-alpha. One patient was treated with lenalidomide (Revlimid) for multiple myeloma, 2 received infliximab, and 1 received etanercept for severe rheumatoid arthritis; the last patient was in a clinical trial of adalimumab for psoriatic arthritis. Skin biopsy specimens revealed diffuse interstitial granulomatous infiltrates of lymphocytes, histiocytes, and eosinophils, palisading degenerated collagen. Withdrawal of the medications led to complete resolution of the skin lesions. CONCLUSION: Interstitial granulomatous dermatitis should be considered in the differential diagnosis of skin lesions occurring in the setting of anti-TNF-alpha therapy.     

Psoriasis and hepatitis C treated with anti-TNF alpha therapy (etanercept)

The treatment of severe psoriasis in patients with concomitant hepatitis-C virus infection is quite difficult because several systemic anti-psoriatic drugs are contraindicated owing to their liver toxicity. Recent observations in the literature suggest that etanercept is an effective and safe therapy for this setting of patients. We present a 45-year-old man with extensive plaque psoriasis and concurrent hepatitis C, successfully treated with 12-month etanercept monotherapy. Regular controls of hepatic enzymes and viral load during the treatment disclosed no worsening of baseline values. This case confirms that etanercept may be a safe option for the therapy of patients with psoriasis and hepatitis-C virus infection.     

Etanercept for psoriasis in the pediatric population: experience in nine patients

Psoriasis commonly affects children and adolescents, and the need for safe, effective therapy is a special consideration in the pediatric population. In recent years, the use of targeted immunomodulatory biologic agents has been increasingly studied for the treatment of psoriasis. Of these, etanercept, a tumor necrosis factor-alpha antagonist, has been approved for the treatment of psoriasis and psoriatic arthritis in adults, and while it is approved for use in juvenile rheumatoid arthritis, formal studies are needed to demonstrate its safety and efficacy for childhood psoriasis. We present our preliminary experience of treating nine pediatric patients with generalized, recalcitrant psoriasis with etanercept therapy.     

银屑病患者抗肿瘤坏死因子α治疗前后血清抗核抗体、抗dsDNA抗体及抗ENA抗体的变化

目的：观察银屑病患者接受抗肿瘤坏死因子α制剂治疗后抗核抗体（ANA）、抗dsDNA抗体和抗可提取性核抗原（ENA）抗体的变化。方法回顾分析32例银屑病患者,其中13例使用英夫利西单抗治疗,19例使用依那西普治疗。英夫利西单抗组第0、2、6周各用药1次,此后每隔8周用药,于每次用药前检测患者ANA、抗dsDNA抗体及ENA的情况和临床症状的变化。依那西普组每周用药2次,每3~6个月检测患者ANA、抗dsDNA抗体及ENA的情况和临床症状的变化。采用银屑病皮损面积和严重度指数（PASI）75、疾病活动评分（DAS）28评估临床疗效,间接免疫荧光法检测血清ANA水平,免疫印迹法和ELISA法检测抗dsDNA抗体水平,免疫印迹法检测抗ENA抗体水平。结果32例银屑病患者临床症状有不同程度缓解。32例抗TNF?α治疗的患者中有7例（21.9%）出现自身抗体,其中英夫利西单抗组中4例治疗（8.3±5.1）个月后出现自身抗体,3例ANA阳性,3例ENA阳性;依那西普组中3例治疗（9.0±3.0）个月后出现自身抗体,3例ANA阳性,1例ENA阳性。结论部分银屑病患者接受抗肿瘤坏死因子α制剂治疗后可出现自身抗体。     

Low-dose etanercept therapy in moderate to severe psoriasis in Korean

Etanercept is a fully humanized soluble tumor necrosis factor (TNF)-alpha receptor that competitively inhibits the interaction of TNF-alpha with cell-surface receptors. It was approved as monotherapy for psoriasis in the USA in 2004, but in Korea, no clinical reports on its use for psoriasis are available. We performed a retrospective analysis of 26 moderate-to-severe psoriasis patients who had been treated with etanercept. Patients received twice-weekly injections of 25 mg etanercept s.c. for at least 4 weeks. When the patients achieved a 50% reduction of the psoriasis area severity index (PASI 50) they received once-weekly injections, then biweekly injections were provided for maintenance. Patients were evaluated biweekly by clinical photographs and PASI scoring. Treatment efficacy was as follows. A PASI 75 was achieved in 14 patients (54%) and the mean number of injections before achieving a PASI 75 was 10 +/- 7.5. Patients whose initial PASI was less than 10 (iPASI < 10) showed an earlier response (2.6 +/- 1.3 weeks) and a higher PASI 75 rate (63%), than with iPASI > or = 10 (6.9 +/- 4.5 weeks, 50%). Eight patients (31%) received additional phototherapy or systemic therapy because of insufficient responses or for faster improvements and they were excluded in the efficacy evaluation. Adverse events were observed in eight patients (31%), but were not serious. This is the first report on the effectiveness of low-dose etanercept regimen on Asian psoriasis patients. Results in this study showed that low-dose etanercept therapy is effective for moderate-to-severe Asian psoriasis patients, and it may be a valuable treatment option even for relatively moderate psoriasis patients not responsive to conventional treatment. In addition, the medical cost was relatively low compared to that of the standard regimen for white patients.