Pharmacodynamic analysis of apremilast in Japanese patients with moderate to severe psoriasis: Results from a phase 2b randomized trial

We evaluated the pharmacodynamic effects of apremilast in 69 patients who were included in biomarker subanalyses of a phase 2b study that demonstrated the long‐term safety and efficacy of apremilast in Japanese adults with moderate to severe psoriasis. The association between cytokine levels and Psoriasis Area and Severity Index (PASI) improvement was evaluated using linear regression and Spearman’s rank correlation coefficient analysis. At baseline, median plasma levels of interleukin (IL)‐17A, IL‐17F and IL‐22 were elevated versus reference values for healthy individuals, whereas tumor necrosis factor‐α levels were close to normal. With apremilast 30 mg b.i.d., there were significant associations between percentage change in PASI score and percentage change in IL‐17A, IL‐17F and IL‐22 levels at week 16. Findings demonstrate that the efficacy of apremilast in psoriasis is associated with inhibition of key cytokines involved in the pathology of psoriasis.     

甲氨蝶呤治疗中、重度银屑病的疗效观察

目的:观察甲氨蝶呤(methotrexate,MTX)治疗中、重度银屑病的临床疗效和安全性。方法:41例银屑病患者每周接受MTX5～15mg静脉滴注治疗1次,共20次。结果:41例患者经过10～20周治疗后,痊愈16例(39.0%),显效17例(41.5%),好转7例(17.1%),无效1例(2.4%),有效率为80.5%,不良反应为纳差、恶心、呕吐、头痛、荨麻疹、月经过多、丙氨酸转氨酶轻度升高。结论:MTX5～15mg每周1次静脉滴注治疗中、重度银屑病安全有效。     

A randomized, double-blind, placebo-controlled study to evaluate the addition of methotrexate to etanercept in patients with moderate to severe plaque psoriasis

Background Etanercept plus methotrexate combination therapy has not been adequately investigated in psoriasis. Objectives To evaluate etanercept plus methotrexate vs. etanercept monotherapy in patients with moderate to severe plaque psoriasis who had not failed prior methotrexate or tumour necrosis factor‐inhibitor therapy. Methods Patients received etanercept 50 mg twice weekly for 12 weeks followed by 50 mg once weekly for 12 weeks and were randomized 1 : 1 to receive methotrexate (7·5–15 mg weekly) or placebo. The primary endpoint was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 24. Results In total, 239 patients were enrolled in each arm. PASI 75 was significantly higher at week 24 for the combination therapy group compared with the monotherapy group (77·3% vs. 60·3%; P < 0·0001). Other PASI improvement scores at week 12 [PASI 75, 70·2% vs. 54·3% (P = 0·01); PASI 50, 92·4% vs. 83·8% (P = 0·01); and PASI 90, 34·0% vs. 23·1% (P = 0·03)] showed similar results as did week 24 PASI 50 (91·6% vs. 84·6%; P = 0·01) and PASI 90 (53·8% vs. 34·2%; P = 0·01). Significantly more patients receiving combination therapy than monotherapy had static Physician’s Global Assessment of clear/almost clear at week 12 (65·5% vs. 47·0%; P = 0·01) and week 24 (71·8% vs. 54·3%; P = 0·01). Adverse events (AEs) were reported in 74·9% and 59·8% of combination therapy and monotherapy groups, respectively; three serious AEs were reported in each arm. Conclusions Combination therapy with etanercept plus methotrexate had acceptable tolerability and increased efficacy compared with etanercept monotherapy in patients with moderate to severe psoriasis.     

Improvements in patient-reported outcomes in moderate-to-severe psoriasis patients receiving continuous or paused etanercept treatment over 54 weeks: the CRYSTEL study

Objective  To assess patient-reported outcomes (PRO) in patients with moderate-to-severe plaque psoriasis receiving continuous or paused etanercept treatment.
Methods  In a multicentre European open-label study, one group ( n  = 352) received continuous therapy: 25 mg subcutaneously (SC) twice weekly (BIW) throughout 54-weeks. The other group ( n  = 359) received paused therapy: 50 mg SC BIW (≤ 12 weeks) until response was adequate by Physician Global Assessment; after psoriasis returned, retreatment (25 mg BIW) was begun. PRO included the Dermatology Life Quality Index (DLQI), EuroQoL-5D (EQ-5D), Hospital Anxiety and Depression Scale (HADS), and the SF-36 Vitality subscale.
Results  At baseline, mean DLQI for patients in the continuous (12.8) and paused group (13.8), indicated significant quality-of-life impairment; mean EQ-5D utility scores were 0.65 and 0.66 for continuous and paused patients, respectively; 30.0% of continuous and 37.0% of paused patients had at least mild symptoms of depression; 40.2% and 48.6%, respectively, had at least mild symptoms of anxiety. At week 54, both groups showed statistically significant ( P  < 0.05) and meaningful improvement in DLQI and EQ-5D scores; improvements in HADS-D, HADS-A, and SF-36 vitality were also significant. Improvements in DLQI and EQ-5D were significantly greater in the continuous arm than the paused arm, but the differences were not meaningful. Differences between arms in HADS and SF-36 Vitality at week 54 were not significant.
Conclusions  At baseline, patients exhibited significant quality-of-life impairment. Both continuous and paused etanercept treatment provided improvements in PRO measures. Either regimen could be considered and care should be individualized.     

Safety and effectiveness of adalimumab in patients with moderate-to-severe psoriasis who had inadequate therapeutic response to prior etanercept

BackgroundFew studies exist that evaluate the therapeutic response among switchers of tumor necrosis antagonists in patients with psoriasis, especially Asian patients.ObjectiveThis study aimed to evaluate the safety and effectiveness of adalimumab in patients with moderate-to-severe psoriasis who had inadequate therapeutic response to prior etanercept.MethodsThis is a single-center, open-labeled, retrospective study on the effects of adalimumab in patients with moderate-to-severe psoriasis who had inadequate therapeutic responses to prior etanercept. We included 13 patients who had received etanercept for at least 3s months but showed inadequate therapeutic response, as defined by less than 50% improvement in psoriasis area and severity index (PASI) 50, compared to baseline after 6 months or less than PASI25 improvement after 3 months in our hospital during 2006–2012. Adalimumab 40 mg was given every other week with a loading dose of 80 mg. Patients were evaluated monthly for safety and effectiveness. PASI, physician global assessment, and scores of scalp lesions were calculated at Weeks 12 and 24. Scalp lesions were assessed separately.ResultsAt Week 12, one patient (7%) had at least PASI90, two (15%) had at least PASI75, four (31%) had at least PASI50, and eight (61.5%) had at least PASI25 response. At Week 24, two patients (15%) had at least PASI90, three (23%) had at least PASI75, six (46%) had at least PASI50, and nine (69%) had at least PASI25 response. No severe adverse events were recorded in our series. For scalp lesion, adalimumab showed similar efficacy to etanercept nonresponders.ConclusionSafety profiles of adalimumab were similar to those of etanercept, and PASI50 was achieved in 46% of patients, who failed prior etanercept therapy, after 24 weeks of adalimumab treatment.     

Safety and efficacy of alefacept, efalizumab, etanercept and infliximab in treating moderate to severe plaque psoriasis: a meta-analysis of randomized controlled trials

Background The relatively recent introduction of biological agents to treat psoriasis presents clinicians with the need to objectively compare and contrast these agents to allow more effective treatment of their patients. Objectives To evaluate and compare the efficacy and safety of biological agents in the treatment of plaque psoriasis. Methods (i) Data sources: Four parallel systematic reviews conducted through July 2006, including peer‐reviewed data and U.S. Food and Drug Administration (FDA) reports. (ii) Study selection: Randomized, controlled, double‐blind, monotherapy trials of alefacept (n = 3), efalizumab (n = 5), etanercept (n = 4) and infliximab (n = 4); 16 studies comprising 7931 patients met inclusion criteria. (iii) Data extraction: Efficacy was measured by Psoriasis Area and Severity Index (PASI) 75 achievement after 10–14 weeks of treatment, using intention‐to‐treat analysis. Safety was evaluated by the incidence of one or more adverse event(s) (AEs) and serious adverse event(s) (SAEs) during 10–30 weeks of treatment. Results Pooled relative risk (RR) and number needed to treat (NNT) of PASI 75 achievement compared with placebo was computed using Mantel–Haenszel methods and the random effects model. All biological agents for psoriasis were efficacious (P < 0·001); however, there was a graded response for achievement of PASI 75: infliximab (RR = 17·40, NNT = 2), etanercept (RR = 11·73, NNT = 3), efalizumab (RR = 7·34, NNT = 4) and alefacept (RR = 3·70, NNT = 8). The risk of one or more AEs was evaluated by RR and number needed to harm (NNH). This was increased in the alefacept (RR = 1·09, P = 0·03, NNH = 15), efalizumab (RR = 1·15, P < 0·001, NNH = 9) and infliximab (RR = 1·18, P < 0·001, NNH = 9) groups compared with placebo. SAEs were increased in a sensitivity analysis of four efalizumab trials (n = 2443, RR = 1·92, P = 0·03, NNH = 60). Conclusions The decreasing rank order for pooled efficacy was infliximab, etanercept, efalizumab and alefacept when compared with placebo. Pooling safety data revealed a previously unreported increased risk of AEs for alefacept, efalizumab and infliximab.     

Patient satisfaction with injection devices: a randomized controlled study comparing two different etanercept delivery systems in moderate to severe psoriasis

Background There is limited information regarding the acceptability of injection devices for biological agents. Objectives The primary objective of the study was to investigate patients’ perceptions on the acceptability of two devices delivering etanercept. The secondary objectives of the study were to explore whether patients’ attributes are associated with preferences. Methods This was a multicentre, open‐label, randomized, parallel‐design study. Adult patients with psoriasis were randomized to receive etanercept 50 mg twice‐weekly subcutaneously for 12 weeks, either as a pre‐filled syringe or as a pre‐filled pen. The primary outcome was the patient satisfaction at week 12 with the injection device, as measured on a 0–10‐point Likert scale. The study was powered to demonstrate non‐inferiority of a pen over a syringe for the primary endpoint. Results A total of 421 patients were randomized. Mean patient satisfaction at week 12 was 8.9 (±1.9) points in the pen group and 7.6 (±2.6) points in the syringe group. There was a statistically significant advantage for the pen compared with the syringe. Multiple correspondence analysis showed that very satisfied patients were the oldest and had had psoriasis for a longer duration, while less satisfied patients were the most anxious and depressed. PASI 75 response was achieved by 61% of patients in the pen group and 57% in the syringe group at week 12. Conclusions This study showed higher patient satisfaction when injecting etanercept with a pen compared with a syringe. Factors associated with lower satisfaction are younger age, anxiety and depression.     

中、重度银屑病的联合疗法

介绍应用系统性药物、外用药及光疗等治疗方法联合治疗中、重度银屑病,阐述了各种联合疗法的优、缺点。大部分联合治疗方法具有增加疗效、减少不良反应及可减少各种药物剂量的作用,对于顽固性银屑病患者尤为适用。     

Efficacy and safety observed during 24 weeks of efalizumab therapy in patients with moderate to severe plaque psoriasis

OBJECTIVE: To assess the efficacy and safety of a 24-week course of efalizumab. DESIGN: Phase 3, randomized, double-blind, parallel-group, placebo-controlled 12-week study followed by a 12-week open-label study. SETTING: Outpatient dermatology clinics.Patients A total of 556 patients with moderate to severe chronic plaque psoriasis who were seeing an outpatient dermatologist were included in the study.Intervention For weeks 1 to 12, the 556 patients were randomized to receive 1 mg/kg of efalizumab weekly or placebo subcutaneously. For weeks 13 to 24, 516 of these patients received 1 mg/kg of efalizumab weekly. MAIN OUTCOME MEASURES: Proportion of patients with a 75% or greater improvement in Psoriasis Area and Severity Index (PASI-75), a 50% or greater improvement in PASI (PASI-50), static Physician's Global Assessment (sPGA) rating of minimal or clear, and improvements in Dermatology Life Quality Index (DLQI), itching scale, and Psoriasis Symptom Assessment (PSA) frequency and severity scores at weeks 12 and 24. Safety was evaluated by reviewing adverse events, laboratory parameters, vital signs, and anti-efalizumab antibodies. RESULTS: At week 12, 26.6% of efalizumab-treated patients achieved PASI-75 and 58.5% achieved PASI-50. After 24 weeks of continuous efalizumab therapy, PASI responses increased: 43.8% of patients achieved PASI-75 and 66.6% achieved PASI-50. The percentage of patients who achieved an sPGA rating of minimal or clear increased from 25.7% to 35.9%. The mean percentage of improvement in all patient-reported outcomes (DLQI, itching scale, and PSA frequency and severity scores) at week 12 was maintained at week 24 (DLQI, 49.2%; itching scale, 42.2%; PSA frequency, 47.6%; PSA severity, 47.3%). There was a decline in overall reported adverse events from weeks 1 to 12 (80.4%) to weeks 13 to 24 (63.2%) without evidence of cumulative toxic effects.Conclusion Extending efalizumab treatment from 12 to 24 weeks leads to improved efficacy and maintenance of quality of life with no evidence of cumulative toxic effects noted in patients with moderate to severe chronic plaque psoriasis.     

Efficacy and safety of briakinumab vs. etanercept and placebo in patients with moderate to severe chronic plaque psoriasis

Background The anti‐interleukin‐12/23p40 monoclonal antibody briakinumab has been shown in a phase II study to be effective psoriasis treatment. Objectives The aim of the current study was to assess the efficacy, safety and tolerability of briakinumab compared with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis. Methods In this phase III, 12‐week study (M10‐114, NCT00691964), 347 patients were randomized in a 2 : 2 : 1 ratio to receive 200 mg briakinumab at weeks 0 and 4 followed by 100 mg briakinumab at week 8 (n = 138); 50 mg of etanercept twice weekly 3–4 days apart at weeks 0–11 (n = 141); or placebo injections matching active treatment (n = 68). The co ‐ primary efficacy endpoints were the proportion of patients achieving a Physician’s Global Assessment (PGA) of 0/1 at week 12, and the proportion of patients achieving a Psoriasis Area and Severity Index (PASI) 75 response at week 12. Results Of the briakinumab‐treated patients, 71·0% achieved a PGA of 0/1 at week 12 as compared with 39·7% of etanercept‐treated patients and 2·9% of placebo‐treated patients, (P < 0·001, for both comparisons). Of the briakinumab‐treated patients 81·9% achieved a PASI 75 response at week 12 as compared with 56·0% of etanercept‐treated and 7·4% of placebo‐treated patients (P < 0·001, for both comparisons). Serious adverse event rates were reported in four (2·9%) patients receiving briakinumab, one (0·7%) patient receiving etanercept and one (1·5%) placebo‐treated patient. Conclusions In patients with moderate to severe psoriasis, briakinumab had superior efficacy to both placebo and etanercept at 12 weeks as administered in this study.