Safety profiles and efficacy of infliximab therapy in Japanese patients with plaque psoriasis with or without psoriatic arthritis,pustular psoriasis or psoriatic erythroderma: Results from the prospective post‐marketing surveillance

A large‐scale prospective post‐marketing surveillance was conducted to evaluate the safety and efficacy of infliximab in Japanese patients with plaque psoriasis, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma. This study was conducted in all psoriasis patients treated with infliximab after its Japanese regulatory approval. Infliximab was administrated at 5 mg/kg at weeks 0, 2 and 6, and every 8 weeks thereafter. Patients were serially enrolled and observed for 6 months to evaluate the safety and efficacy. The safety and efficacy were evaluated in 764 and 746 patients, respectively. Incidences of any and serious adverse drug reactions were 22.51% and 6.94%, respectively, and those of any and serious infusion reactions were 6.15% and 1.31%, respectively, which were comparable with the results in the post‐marketing surveillance with 5000 rheumatoid arthritis patients in Japan. Major adverse drug reactions during the follow‐up period were infections (5.10%) including pneumonia, cellulitis and herpes zoster, however, no tuberculosis was observed. The safety profiles were equivalent, regardless of the psoriasis types. No new safety problems were identified. The response rates on global improvement and median improvement rate of Psoriasis Area and Severity Index in all patients were 88.0% and 85.0%, respectively. Of note, the efficacy was equivalent for each psoriasis type as well as for each body region. Infliximab was also effective in pustular psoriasis symptoms, joint symptoms and nail psoriasis, as well as improvement of quality of life. Infliximab was confirmed to be highly effective and well tolerated in treating refractory psoriasis, including pustular psoriasis and psoriatic erythroderma.     

Successful management of infliximab‐induced generalized pustular psoriasis without therapy discontinuation in a patient with psoriatic arthritis

While infliximab has been shown to be paradoxically associated with the development of pustular psoriasis in patients with rheumatoid arthritis, spondyloaripathies, juvenile idiopathic, and inflammatory bowel disease, there are few cases of pustular psoriasis induced by infliximab in patients with psoriasis. We here present a 55‐year‐old female patient with longstanding plaque psoriasis and psoriatic arthritis who developed generalized pustular psoriasis 1 month after the fifth infusion of infliximab. Given the lack of other side effects and the rapid initial response of the underlying psoriatic arthritis, we opted against discontinuing infliximab therapy, and the sixth infusion of infliximab was administered 10 days ahead of schedule. Topical corticosteroids were added for the management of pustular lesions on initial presentation. One week after the sixth infusion, the pustular psoriatic lesions almost completely disappeared. No recurrence of pustular psoriasis was observed during the 3‐month follow‐up. Our experience shows that pustular lesions associated with infliximab can be successfully managed with topical corticosteroids without discontinuing infliximab therapy or compromising therapeutic benefit seen upon the underlying condition.     

Oral tofacitinib efficacy,safety and tolerability in Japanese patients with moderate to severe plaque psoriasis and psoriatic arthritis: A randomized,double‐blind,phase 3 study

Tofacitinib is an oral Janus kinase inhibitor that is being investigated for psoriasis and psoriatic arthritis. Japanese patients aged 20 years or more with moderate to severe plaque psoriasis and/or psoriatic arthritis were double‐blindly randomized 1:1 to tofacitinib 5 or 10 mg b.i.d. for 16 weeks, open‐label 10 mg b.i.d. for 4 weeks, then variable 5 or 10 mg b.i.d. to Week 52. Primary end‐points at Week 16 were the proportion of patients achieving at least a 75% reduction in Psoriasis Area and Severity Index (PASI75) and Physician's Global Assessment of “clear” or “almost clear” (PGA response) for psoriasis, and 20% or more improvement in American College of Rheumatology criteria (ACR20) for patients with psoriatic arthritis. Safety was assessed throughout. Eighty‐seven patients met eligibility criteria for moderate to severe plaque psoriasis (5 mg b.i.d., n = 43; 10 mg b.i.d., n = 44), 12 met eligibility criteria for psoriatic arthritis (5 mg b.i.d., n = 4; 10 mg b.i.d., n = 8) including five who met both criteria (10 mg b.i.d.). At Week 16, 62.8% and 72.7% of patients achieved PASI75 with tofacitinib 5 and 10 mg b.i.d., respectively; 67.4% and 68.2% achieved PGA responses; all patients with psoriatic arthritis achieved ACR20. Responses were maintained through Week 52. Adverse events occurred in 83% of patients through Week 52, including four (4.3%) serious adverse events and three (3.2%) serious infections (all herpes zoster). No malignancies, cardiovascular events or deaths occurred. Tofacitinib (both doses) demonstrated efficacy in patients with moderate to severe plaque psoriasis and/or psoriatic arthritis through 52 weeks; safety findings were generally consistent with prior studies.     

阿达木单抗治疗重度银屑病14例临床疗效及安全性观察

目的 观察阿达木单抗治疗重度银屑病的临床疗效及安全性。方法 在2015 年12月至2017年8月就诊于南京医科大学附属无锡第二医院的重度银屑病患者中选择传统治疗无效的患者14例,给予阿达木单抗单药皮下注射治疗,初始剂量80 mg,1周时给予40 mg,以后每2周给予40 mg,分别于第4、8、12周时记录患者银屑病皮损面积和严重度指数（PASI）及疾病严重程度评分（PGA）改善情况,观察临床疗效及药物不良反应。合并关节病性银屑病患者的关节改善采用美国风湿病协会（ACR）有关类风湿关节炎改善的ACR20作为评价指标。结果 14 例患者均接受至少12 周疗程的药物治疗。4 周时,8 例达PASI 50;8周时,8例达PASI 75,其中2例达PASI 90;12周时,14例达PASI 75,其中7例达PASI 90,3例达PASI 100。治疗前14例患者PGA为（4.92 ± 0.02）分,12周时下降至（1.21 ± 0.02）分。3 例合并关节病性银屑病患者,关节症状改善明显,8周时2例达ACR20,12周时3例达ACR20。所有患者均未出现严重感染或恶性肿瘤等严重的药物不良反应。3例患者出现荨麻疹,给予抗组胺药后症状缓解。结论 阿达木单抗隔周皮下注射治疗重度银屑病疗效显著,不良反应较少,为传统治疗无效的重度银屑病患者的治疗提供了新选择。     

司库奇尤单抗300 mg和150 mg治疗银屑病性关节炎长期疗效比较meta分析

目的：比较司库奇尤单抗300 mg和150 mg治疗银屑病性关节炎(PsA)长期疗效的差异。方法：在Pubmed、Cochrane Library、 MEDLINE、EMBASE、中国知网、万方数据库和维普数据库中检索司库奇尤单抗300 mg和150 mg治疗PsA的随机对照试验（RCTs），提取相关数据，用RevMan5.3软件进行meta分析。结果：根据纳入标准共纳入5篇文献进行分析，包括3项RCTs。52周时，司库奇尤单抗300 mg治疗后美国风湿病学会疗效标准改善20%、50%及70%（ACR 20/50/70）的应答率、起止点炎缓解率、指趾炎缓解率与150 mg相比无显著差异，而300 mg治疗的PASI提高75%、90%（PASI 75/90）应答率均高于150 mg（P=0.002，0.01）。52周时，接受过肿瘤坏死因子抑制剂治疗(TNFi-exposed)的患者司库奇尤单抗300 mg治疗后ACR 20和PASI 75应答率均高于150 mg（P=0.006，0.04），而在未接受过肿瘤坏死因子抑制剂治疗(TNFi-naive)患者中300 mg和150 mg治疗后ACR 20和PASI 75应答率无显著差异(P=0.85，0.59)。结论：在长期疗效方面，司库奇尤单抗300 mg对PsA患者关节损害及功能的改善与150 mg无显著差异，而对皮损的改善有优势；对TNFi-exposed的PsA患者，司库奇尤单抗300 mg比150 mg有更好的疗效。     

Efficacy and safety of ixekizumab treatment for Japanese patients with moderate to severe plaque psoriasis,erythrodermic psoriasis and generalized pustular psoriasis: Results from a 52‐week,open‐label,phase 3 study (UNCOVER‐J)

Psoriasis, a chronic, immune‐mediated skin disease characterized by red, scaly plaques, affects approximately 0.3% of the population in Japan. The aim of this open‐label study was to evaluate the long‐term efficacy and safety of ixekizumab, a humanized, anti‐interleukin‐17A monoclonal antibody, in Japanese patients with plaque psoriasis (n = 78, including 11 psoriatic arthritis), erythrodermic psoriasis (n = 8) and generalized pustular psoriasis (n = 5). Ixekizumab was administrated s.c. at baseline (week 0, 160 mg), from weeks 2 to 12 (80 mg every 2 weeks), and from weeks 16 to 52 (80 mg every 4 weeks). At week 52, 92.3% of patients with plaque psoriasis achieved Psoriasis Area and Severity Index (PASI) 75, 80.8% achieved PASI 90, 48.7% achieved PASI 100, and 52.6% had remission of plaques (by static Physician Global Assessment, sPGA [0]). Difficult to treat areas of psoriasis (nail or scalp) also responded to ixekizumab. All patients with psoriatic arthritis who were assessed (5/5) achieved an American College of Rheumatology 20 response. Most patients with erythrodermic psoriasis or generalized pustular psoriasis responded to ixekizumab and the clinical outcome was maintained over 52 weeks (75% and 60% of patients achieved sPGA [0, 1] at week 52, respectively). Mostly mild or moderate treatment‐emergent adverse events were reported by 79 of 91 patients; the most common were nasopharyngitis, eczema, seborrheic dermatitis, urticaria and injection site reactions. In conclusion, 52‐week ixekizumab treatment was efficacious and well tolerated in Japanese patients with plaque psoriasis. Efficacy was also observed in patients with erythrodermic psoriasis, generalized pustular psoriasis and psoriatic arthritis.     

Infliximab for the treatment of psoriasis in Greece: 4 years of clinical experience at a single centre

Background Infliximab, a chimeric monoclonal antibody, has been shown to be effective for moderate to severe psoriasis. Clinical experience with long‐term infliximab therapy for psoriasis is accumulating, and it is therefore important to share our experience with its use in real‐life clinical practice. Objectives To report our experience with infliximab (Remicade^®; Schering Plough, Kenilworth, NJ, U.S.A.) for the treatment of moderate to severe plaque psoriasis (and/or arthritis) from a single clinic in Greece. Patients and methods Between August 2004 and March 2008, 62 patients presenting to our clinic with moderate to severe psoriasis were treated with infliximab. Disease phenotype, clinical course, disease severity and adverse events were assessed throughout the treatment period. Results Infliximab resulted in a reduction of median Psoriasis Area and Severity Index (PASI) of 70% at week 6 and 84·4% at week 14. Nineteen patients who have completed 1 year on infliximab treatment experienced sustained efficacy with a median PASI improvement of 92·16% and a Physician’s Global Assessment (PGA) of ‘clear’ or ‘almost clear’, while nine patients have reached approximately 20 months of continuous therapy. All patients with psoriatic arthritis showed marked improvement in their clinical symptoms following the first infusion. Eight patients (12·9%) experienced adverse events that required discontinuation of treatment. There were no statistically significant differences in PASI and Dermatology Life Quality Index (DLQI) scores between patients with arthritis and those with only skin lesions, or between those who received methotrexate, either from the beginning or during infliximab therapy, and those who did not receive methotrexate at all. Selected patients of interest are discussed. Conclusions The above data confirm previous reports that treatment with infliximab is an efficacious and safe option for patients with moderate to severe plaque psoriasis (and/or arthritis). Long‐term follow‐up, continued pharmacovigilance, and controlled comparative studies will be required to fully evaluate its use in the treatment of psoriasis.     

Use of biological drugs in patients with psoriasis and psoriatic arthritis in Italy: Results from the PSONG survey

This Italian multicenter retrospective study compared the drug survival and efficacy of different anti‐TNF agents in psoriasis (PsO) and psoriatic arthritis (PsA) patients. A database of PsO/PsA patients treated with adalimumab, etanercept, and infliximab from May 2013 to May 2014 was analyzed. PASI 75, 90, and 100 was calculated at each time point to evaluate efficacy. Drug survival rate and probability of maintaining PASI response were evaluated. The impact of dependent variables on probability of PASI 75 loss was evaluated by logistic regression. 1,235 patients were included, 577 with PsO and 658 with PsA. Highest survival rates were observed with adalimumab followed by etanercept and infliximab in PsO and PsA patients. The probability of maintaining PASI response was significantly higher for adalimumab followed by infliximab. For PsO patients, the odds of losing PASI 75 was higher in etanercept‐treated patients (OR: 8.1; 95% CI: 4.2–15.6, p < .001) or infliximab (OR: 6.6; 95% CI: 2.6–16.3, p < .001) vs. adalimumab. Likewise, for PsA patients the odds of losing PASI 75 was higher in etanercept‐treated patients (OR: 2.3; 95% CI: 1.4–3.8, p = .01) or infliximab (OR: 2.2; 95% CI: 1.1–4.1, p = .018) vs. adalimumab. Adalimumab could be the best therapeutic option over other anti‐TNF agents for the treatment of PsO and PsA patients.     

A follow-up study in 28 patients treated with infliximab for severe recalcitrant psoriasis: evidence for efficacy and high incidence of biological autoimmunity

BACKGROUND: Infliximab, an antitumour necrosis factor-alpha chimeric monoclonal antibody, is effective for the treatment of severe psoriasis. While the induction of antinuclear antibodies (ANA) and antidouble-stranded-DNA antibodies (anti-dsDNA-ab) is frequently observed in patients with rheumatoid arthritis and Crohn disease receiving infliximab, the incidence of induced biological and clinical autoimmunity remains unknown in the context of psoriasis. OBJECTIVES: To investigate biological and clinical signs of autoimmunity in 28 patients receiving infliximab for severe, recalcitrant forms of psoriasis, and the clinical response to treatment. METHODS: Twenty-eight patients, 15 men and 13 women (median age 39.4 years) with psoriasis refractory to three or more systemic treatments were included. Twenty presented with plaque-type psoriasis [median Psoriasis Area and Severity Index (PASI) score 25.9; range 7.2-48], five with psoriatic erythroderma (median PASI score 54; range 48-72) and three with generalized pustular psoriasis (GPP). Psoriatic arthritis was present in 13 patients (46.4%). Infliximab 5 mg kg(-1) was given at week (W) 0, W2, W6 and every 8 weeks thereafter. Clinical data were assessed at baseline and before each infusion. Detection of ANA and of IgM and IgG anti-dsDNA-ab were performed at baseline and at W22 by immunofluorescence and enzyme-linked immunosorbent assay, respectively. RESULTS: The mean number of infliximab infusions was 5.5 (range 2-15). Among patients with plaque-type and erythrodermic psoriasis, 17 of 25 (68%) and three of five reached a PASI improvement of 75% or more, respectively, while rapid improvement of clinical and biological signs was observed in all three patients with GPP. The prevalence of positive detection of ANA raised from 12% at baseline to 72% at W22 (P = 0.0001), an increase which was also observed for IgM anti-dsDNA-ab (68% vs. 0%, P < 0.0001), while no significant change was observed for the IgG isotype (16% vs. 0%, P = 0.125). Three patients developed nonerosive polyarthritis, without any other criteria for systemic lupus. CONCLUSIONS: The incidence of biological autoimmunity is high in patients with refractory psoriasis receiving infliximab. The concomitant onset of polyarthritis in three cases raises the need to investigate the incidence of autoimmune manifestations in psoriatic patients receiving infliximab in further large-scale studies.     

Effects of etanercept on C-reactive protein levels in psoriasis and psoriatic arthritis

Background  C-reactive protein (CRP), an inflammation biomarker, indicates cardiovascular risk and is elevated in psoriasis. The effect of etanercept on CRP in psoriasis has not been previously examined.
Objectives  The primary objective was to examine the effect of etanercept on CRP levels from baseline to week 12 compared with placebo. Secondary objectives included assessment of baseline CRP and relationships between CRP and body mass index (BMI), statin drug use, and Psoriasis Area and Severity Index (PASI) scores.
Methods  A retrospective analysis was conducted of CRP levels from patients with psoriasis who participated in a randomized, double-blind, placebo-controlled, U.S. registrational study. Data were analysed separately if patients self-reported psoriatic arthritis.
Results  Baseline CRP levels were elevated in patients with psoriasis with and without psoriatic arthritis. CRP was significantly reduced in both groups after 12 weeks of etanercept treatment. Patients with psoriasis with psoriatic arthritis and patients with higher BMIs had higher median baseline CRP values and greater reduction of CRP values compared with those without psoriatic arthritis and those with lower BMIs. Etanercept lowered CRP levels in statin users and nonusers. Regression analyses revealed an association between baseline PASI score and baseline CRP independent of BMI in patients with psoriasis.
Conclusions  Patients with moderate to severe plaque psoriasis, with or without psoriatic arthritis, have increased systemic inflammation demonstrated by elevated CRP levels. In psoriasis without psoriatic arthritis, skin disease activity is associated significantly with CRP elevation, independent of BMI, age and sex. Etanercept reduced CRP levels in all but the normal weight psoriasis group without psoriatic arthritis.     

司库奇尤单抗治疗七例银屑病疗效评价

目的：评价司库奇尤单抗治疗银屑病的疗效和安全性。方法：选取中重度斑块状银屑病患者及泛发性脓疱型银屑病患者,给予司库奇尤单抗,300 mg/次,0～4周每周一次,后每4周一次,并分别于治疗前、1周后、4周后、8周后记录斑块状银屑病患者的银屑病皮损面积和严重度指数(PASI)、泛发性银屑病患者银屑病症状量表(PSS)评分。结果：共治疗6例斑块状银屑病和1例脓疱型银屑病患者,所选的患者均接受至少8周的司库奇尤单抗治疗,起效时间为（1.6±0.73)天;治疗4周时,6例斑块状银屑病患者中全部达到PASI 75,3例达到PASI 90;脓疱型患者PSS评分为2。治疗8周时6例斑块状银屑病患者均达到PASI 100;脓疱型患者PSS评分为0。所有患者治疗期间均未出现严重的药物不良反应。结论：司库奇尤单抗治疗中重度银屑病起效迅速,疗效显著,不良反应少。     

Biologic therapy for acrodermatitis continua of Hallopeau: Successful treatment with secukinumab and review of the literature

Acrodermatitis continua of Hallopeau (ACH) is a rare pustular psoriasis variant refractory to many conventional treatments. We report the successful treatment with secukinumab of a patient with a long history of ACH with marked onychodystrophy with frank pustulosis on the nail bed and with accompanying arthritis. Blockade of the IL‐17 receptor A has shown promise in the treatment of psoriatic erythroderma and generalized pustular psoriasis not responsive to conventional treatment. A rapid response was observed in our patient, in both skin lesions and arthritic symptoms, underlining the ability of secukinumab to improve symptoms beyond those of plaque psoriasis.     

Dramatic impact of a Psoriasis Area and Severity Index 90 response on the quality of life in patients with psoriasis: an analysis of Japanese clinical trials of infliximab

European S3 Guidelines on the systemic treatment of psoriasis in 2009 propose 75% or more improvement in the Psoriasis Area and Severity Index from baseline (PASI 75) and a Dermatology Life Quality Index (DLQI) of 0 or 1 as treatment goals. However, the relationship of these two parameters is yet to be clarified. Herein, we analyzed the data pooled from two Japanese phase III clinical trials on psoriasis with infliximab to clarify the PASI response necessary to achieve a DLQI of 0 or 1. Of the 90 patients, the mean percent improvement in PASI at week 50 or 66 was 74.5%, and the PASI 75 and PASI 90 response rates were 66.7% and 46.7%, respectively; no difference in the improvement was noted among the body areas. Significant improvements in nail psoriasis were also observed. A negative correlation was shown between the improvement in PASI and DLQI. Patients who achieved a PASI 90 response had a significantly higher percentage of achieving a DLQI of 0 or 1 than the patients who achieved a PASI 75 but not a PASI 90 response. The median serum trough level of infliximab was maintained at 2 μg/mL or more in the PASI 90 responders, whereas it was less than 1 μg/mL at week 30 and on in the others. The present results demonstrate that a PASI 90 response is necessary to achieve a DLQI of 0 or 1. Infliximab is considered a useful drug in meeting the treatment goal of achieving a DLQI of 0 or 1 through the attainment of a PASI 90 response.     

Combination of skin,joint and quality of life outcomes with etanercept in psoriasis and psoriatic arthritis in the PRESTA trial

Background Psoriasis and psoriatic arthritis (PsA) affect skin, and/or joints and quality of life (QoL). Objective To better assess the success in multiple attributes in subjects with both active psoriasis and PsA, the objective was to quantify the proportion of those who achieved substantial improvement in a composite measure of skin symptoms, joint manifestations, and QoL, on one of two treatment regimens. Methods Subjects (n = 752) with psoriasis and PsA (mean age: 46.5 years, 62.9% male) received etanercept (ETN) 50 mg twice weekly (BIW; n = 379) or 50 mg weekly (QW; n = 373) for 12 weeks, followed by open‐label ETN 50 mg QW for 12 weeks. Skin and joint symptoms and QoL were assessed using psoriasis area and severity index (PASI), American College of Rheumatology criteria (ACR) and Euro‐QoL (EQ‐5D), respectively. Results By week 24, 30.6% and 25.8% of subjects receiving ETN 50 mg BIW/QW and ETN 50 mg QW/QW, respectively (P = 0.198) achieved the composite measure of efficacy for skin plus joints plus QoL (PASI 75 + ACR 50 + EQ‐5D VAS >82). Conclusion At 24 weeks, 25.8–30.6% met the triad of rigorous efficacy outcomes. Evaluation of treatment efficacy should address the multiple components of this disease complex; therefore it may be important to consider this composite measure in future trials.     

Guselkumab治疗银屑病关节炎疗效及安全性meta分析

目的：评价guselkumab治疗银屑病关节炎的疗效及安全性。方法：检索Pubmed、Embase、Cochrane Library、维普期刊数据库、万方数据库及中国知网数据库与guselkumab治疗银屑病关节炎的随机对照试验（RCT），检索时间均为建库起至2020年4月。文献质量根据Cochrane系统评价进行评估。两位评论员独立选择文献并收集数据。文献用Revman 5.3软件进行meta分析。结果：纳入符合标准的文献共3篇，共涉及896例银屑病关节炎患者，试验组475例，对照组421例。meta分析结果示皮下注射guselkumab与安慰剂比较，在第24周时能显著提高达到ACR 20，ACR 50，ACR 70和PASI 75，PASI 90患者的例数；HAQ-D1较基线提高0.35的患者例数也高于安慰剂组；Guselkumab与安慰剂比较，总的不良事件的发生率方面差异无统计学意义。结论：Guselkumab是改善银屑病关节炎安全、有效的选择。     

Treatment of palmoplantar psoriasis with infliximab: a randomized,double‐blind placebo‐controlled study

Background Palmoplantar psoriasis is a difficult to treat variant of plaque psoriasis. Objective To study the safety and efficacy of infliximab in non‐pustular palmoplantar psoriasis. Methods Patients with non‐pustular palmoplantar psoriasis affecting at least 10% of their palms and soles and with a modified palmoplantar psoriasis area and severity index (m‐PPPASI) of at least eight were recruited. Patients were randomized (1:1) to receive infliximab 5 mg/kg or placebo at weeks 0, 2 and 6. Patients initially randomized to placebo received infliximab at weeks 14, 16 and 20 whereas patients randomized to infliximab received additional infliximab infusions every 8 weeks until week 22. Results Twenty four (24) patients were randomized in this study. At week 14, 33.3% and 66.7% of patients treated with infliximab achieved m‐PPPASI 75 and m‐PPPASI 50 respectively compared to 8.3% for both m‐PPPASI 75 (P = 0.317) and m‐PPPASI 50 (P = 0.009) for patients randomized to placebo. A reduction of 50.3% in the mean surface area of palms and soles affected with psoriasis was seen at week 14 in patients randomized to infliximab as compared to an increase of 14.9% in patients randomized to placebo (P = 0.009). Conclusions This pilot study did not reach its primary endpoint of m‐PPPASI 75 at week 14. However, infliximab was observed to be more efficacious than placebo in improving PPSA and with respect to the percentage of patients reaching m‐PPPASI 50 at week 14. Larger and longer term studies are needed for severe patients to better assess the efficacy of infliximab in palmoplantar psoriasis.     

Efficacy and safety of infliximab vs. methotrexate in patients with moderate-to-severe plaque psoriasis: results of an open-label, active-controlled, randomized trial (RESTORE1)

Background Infliximab is indicated for treatment of moderate‐to‐severe plaque psoriasis in adults whose disease cannot be controlled with other systemic therapies, including methotrexate (MTX). To date, no studies have directly compared the efficacy and safety of infliximab and MTX. Objectives To compare the efficacy and safety of infliximab vs. MTX in adults with moderate‐to‐severe plaque psoriasis. Methods MTX‐naïve patients (n = 868) were randomized 3 : 1 to receive infliximab 5 mg kg^?1 at weeks 0, 2, 6, 14 and 22 or MTX 15 mg weekly with a dose increase to 20 mg weekly at week 6 if the Psoriasis Area and Severity Index (PASI) response was < 25%. At week 16, patients with < PASI 50 response could switch treatment groups. The primary efficacy endpoint was PASI 75 response at week 16. Major secondary efficacy endpoints were PASI 75 response at week 26, and the proportion of patients achieving a Physician’s Global Assessment (PGA) score of cleared (0) or minimal (1) at weeks 16 and 26. Others included Dermatology Life Quality Index, 36‐Item Short Form Health Survey, and PGA, PASI 50, PASI 75 and PASI 90 responses over time. Results The primary endpoint was achieved by a significantly greater proportion of infliximab‐treated patients (508/653, 78%) than MTX‐treated patients (90/215, 42%; P < 0·001). Key secondary endpoints also were achieved by a greater proportion of infliximab‐treated patients. Similar responses were observed at week 26 in patients who switched from MTX to infliximab at week 16. Overall adverse event (AE) incidence was comparable between groups, but incidence of serious and severe AEs was slightly higher in the infliximab group. Conclusions Infliximab was well tolerated and more efficacious than MTX in patients with moderate‐to‐severe plaque psoriasis. Infliximab also was efficacious in patients who failed MTX and switched to infliximab.     

Treatment of severe recalcitrant plaque psoriasis with single-dose intravenous tumour necrosis factor-alpha antibody (infliximab)

Infliximab is a chimeric anti-tumour necrosis factor-alpha antibody that has been demonstrated to have marked efficacy in the treatment of psoriasis. Seven patients with chronic plaque psoriasis were treated with single-dose intravenous infliximab (5 mg/kg), and the Psoriasis Area and Severity Index (PASI) and Dermatology Life Questionnaire Index (DLQI) were used as a measure of treatment efficacy. There was an average improvement in PASI scores of 69% at 2 weeks post infusion. There was an improvement in DLQI of 61%. Four of the seven patients were also seen at 10 weeks post infusion and the improvement in PASI and DLQI was sustained. All patients tolerated the initial infusion well without adverse events. The results indicate that single-dose infliximab is an effective and efficacious therapy for recalcitrant psoriasis and has a prolonged therapeutic effect.     

Two years of experience with etanercept in recalcitrant psoriasis

BACKGROUND: The safety and efficacy of etanercept have been demonstrated in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Placebo-controlled trials have indicated the efficacy of etanercept in moderate to severe psoriasis. OBJECTIVES: To observe the efficacy and safety profile of etanercept in patients with severe psoriasis resistant to other systemic agents over a 2-year period. METHODS: In this retrospective study, 49 patients were treated with etanercept between March 2004 and March 2006. All patients were screened for tuberculosis with tuberculin test and a chest X-ray. Thirty-nine patients started on etanercept 25 mg twice weekly (BIW) and 10 started at 50 mg BIW when judged to be clinically indicated. In 19 of those on 25 mg BIW, the dose was increased to 50 mg BIW because of poor response and psoriasis flaring. Response to treatment was assessed by Psoriasis Area and Severity Index (PASI) and static Physician Global Assessment (PGA). Patients were reviewed at 8-week intervals, when clinical response and adverse effects were noted. RESULTS: Forty-four patients (90%) had chronic plaque psoriasis, two (4%) were suberythrodermic, one (2%) had palmoplantar pustular psoriasis and two (4%) had acrodermatitis continua of Hallopeau. At least 75% reduction in PASI was achieved in 47% of patients at week 24 and 66% at week 48. At week 24, 44% had a PGA score of excellent, and at week 48, 58% scored excellent. In 12 who cleared, etanercept was stopped. Ten of these relapsed and etanercept was recommenced, while two remained in remission (mean 12.5 weeks). One patient developed extrapulmonary tuberculosis. CONCLUSIONS: Etanercept was effective in severe psoriasis recalcitrant to other systemic medication. The drug was well tolerated. Development of tuberculosis in one patient underlines the need for rigorous tuberculosis screening.     

Treatment of psoriasis with the chimeric monoclonal antibody against tumor necrosis factor alpha,infliximab

BACKGROUND: Psoriatic skin lesions in patients with Crohn's disease or psoriatic arthritis have shown improvement during infliximab treatment. OBJECTIVE: The purpose of our study was to systematically assess the effects of infliximab in patients with psoriatic skin lesions. METHODS: Eight patients with severe psoriasis were enrolled in an open-label clinical trial. Patients received infliximab, 5 mg/kg, intravenously at weeks 0, 2, and 6. The Psoriasis Area and Severity Index (PASI) was used to monitor disease activity at weeks 0, 2, 4, 6, 8, 10, and 14. Week 10 was the end point of the treatment phase; week 14 was the follow-up end point. Pruritus was assessed on a scale of 0 to 3. Histologic sections were prepared from biopsy specimens of uninvolved skin and of psoriatic lesions at weeks 0, 1, and 10 to measure epidermal thickness with the use of a microscopic micrometer grid. RESULTS: The PASI diminished from 21.8 +/- 4.2 (mean +/- SE) at week 0 to 3.4 +/- 2.0 at week 10, corresponding to 10.7% +/- 4.3% of the original values (100%); on follow-up at week 14, the PASI was 7.1 +/- 2.7 (or still 33.3% +/- 11.3% of the values at week 0). Pruritus decreased from 2.5 +/- 0.26 at week 0 to 0.43 +/- 0.2 at week 10 and to 0.83 +/- 11.3 at week 14. Likewise, epidermal thickness (acanthosis) tended to normalize from 0.41 +/- 0.06 mm at week 0 to 0.14 +/- 0.02 mm at week 10. No adverse effects other than fatigue during infusion on some occasions were reported. CONCLUSION: Although psoriasis tends to recur beyond 2 months of the infusions, this open study provides evidence that infliximab is an effective treatment.