Combining etanercept with traditional agents in the treatment of psoriasis: a review of the clinical evidence

Psoriasis is a chronic, systemic inflammatory disorder manifesting primarily in skin and potentially in joints, frequently necessitating treatment with conventional systemic therapies, phototherapy or biological agents. Patients with moderate to severe disease suffer a diminished quality of life, experience significant comorbidities and have a higher mortality. Although traditional treatments are effective in the short‐term, their use is often limited by concerns over long‐term toxicity, including end‐organ damage and risk of malignancy. Combination therapy is a commonly used approach and is often more effective than any single agent. Lower doses of two treatments in combination can also minimize potential side effects from a single agent at higher doses. Etanercept is a recombinant human tumour necrosis factor (TNF)α receptor (p75) protein fused with the Fc portion of IgG1 that binds to TNFα. This article reviews the evidence on the efficacy and safety of etanercept in combination with methotrexate, acitretin, narrowband UVB and cyclosporin. The largest body of evidence assesses the combination with methotrexate, although evidence is available for the other combinations. Data suggest that although highly effective as monotherapy, etanercept in combination with a conventional systemic agent can enhance efficacy and allow drug sparing. Potentially, the combination may also result in faster treatment responses and permit safe transitioning from one systemic agent to another. Evidence to date suggests that these benefits can be achieved without significant additional toxicity, although long‐term data on the efficacy and safety of the combination in psoriatic populations is limited and further evaluation is warranted.     

Anti–tumour necrosis factor-α therapy increases body weight in patients with chronic plaque psoriasis: a retrospective cohort study

Background Chronic plaque psoriasis is associated with overweight or obesity. Anti–tumour necrosis factor‐α (anti‐TNF‐α) treatments are now frequently used in psoriasis management. TNF‐α is deeply involved in body weight homeostasis, which may be affected by TNF‐α–targeted therapy. Objective To investigate whether anti‐TNF‐α treatments is associated with changes in body weight in patients with chronic plaque psoriasis. Methods We performed a retrospective controlled analysis comparing the variations in body weight and body mass index (BMI) in three closed cohorts of psoriatic patients during a 6‐month treatment with etanercept (N = 58), infliximab (N = 40) or methotrexate (N = 43). Results We observed a body weight increment of 1.5 ± 2.7 kg (mean ± SD; P = 0.0002) and 2.5 ± 3.3 kg (P = 0.004) in patients treated with etanercept and infliximab, respectively. In contrast, a non‐significant change (0.6 ± 1.4 kg; P = 0.4) was measured in patients treated with methotrexate. The BMI increased with 0.5 ± 0.5 (P = 0.01) and 0.8 ± 1 (P = 0.003) points in patients treated with etanercept and infliximab, respectively, whereas it did not change (< 0.2 ± 0.5; P = 0.06) in patients treated with methotrexate. About one fourth of patients experienced a 4‐ to 10‐kg weight gain. Differences in body weight variations among patients treated with anti‐TNF‐α therapies and methotrexate were statistically significant (P = 0.0005). We could not identify clinical parameters predicting this phenomenon. Conclusions Patients with psoriasis treated with long‐term anti‐TNF‐α therapies may manifest a body weight gain. This effect should be taken into account in the global approach to patients with psoriasis.     

Once weekly administration of etanercept 50 mg is efficacious and well tolerated in patients with moderate-to-severe plaque psoriasis: a randomized controlled trial with open-label extension

Background In previous studies, etanercept 25 mg twice weekly (BIW) or 50 mg BIW significantly reduced disease severity in patients with plaque psoriasis and demonstrated a favourable safety profile. Objectives To assess the efficacy and safety of etanercept 50 mg administered once weekly (QW) compared with placebo in patients with moderate‐to‐severe plaque psoriasis over 24 weeks. Methods This study was conducted in two parts: (i) a 12‐week, double‐blind, placebo‐controlled phase, in which patients received etanercept 50 mg QW or placebo QW; and (ii) a 12‐week, open‐label extension phase, in which all patients received etanercept 50 mg QW. Primary endpoint was a 75% or greater improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) at week 12. Secondary endpoints included percentage PASI improvement and Physician’s Global Assessment (PGA). Results One hundred and forty‐two patients were analysed in the double‐blind phase; 126 patients entered the open‐label phase. At week 12, significantly more patients receiving etanercept 50 mg QW (37·5%) achieved PASI 75 response than patients receiving placebo (2·2%; P < 0·0001). At week 24, 71·1% in the etanercept–etanercept group and 44·4% in the placebo–etanercept group achieved PASI 75. Mean percentage of PASI improvement from baseline was 55·4% with etanercept vs. 9·4% worsening with placebo at week 12 (P < 0·0001), with 77·4% and 57·7% improvement in the etanercept–etanercept and placebo–etanercept groups at week 24. A PGA score of 0–1 (clear–almost clear) was achieved by 64% and 42% in the etanercept–etanercept and placebo–etanercept groups at week 24, respectively. Etanercept 50 mg QW was well tolerated. No deaths, serious infections, opportunistic infections (including tuberculosis), demyelinating disorders, malignancies or new safety signals were reported. Conclusions Nearly three‐quarters of patients with moderate‐to‐severe psoriasis receiving etanercept 50 mg QW achieved significant improvement in disease severity over 24 weeks. This study also showed a favourable tolerability and safety profile with etanercept 50 mg QW.     

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.     

A global phase III randomized controlled trial of etanercept in psoriasis: safety, efficacy, and effect of dose reduction

BACKGROUND: In previous studies, etanercept significantly improved plaque psoriasis and was well tolerated. OBJECTIVES: To examine further the efficacy and safety of etanercept and to assess maintenance of treatment effect after dose reduction of etanercept. METHODS: In this multicentre 24-week study in the U.S.A., Canada and Western Europe, patients were at least 18 years old; had active, clinically stable plaque psoriasis involving at least 10% of body surface area; had a minimum Psoriasis Area and Severity Index (PASI) of 10 at screening; and had received or were a candidate to receive systemic psoriasis therapy or phototherapy. During the first 12 weeks of the study, patients were randomly assigned to receive by subcutaneous injection etanercept twice weekly (BIW) at a dose of 50 mg or 25 mg, or placebo BIW in a double-blind fashion. During the second 12 weeks, all patients received etanercept 25 mg BIW. The primary endpoint was a 75% or greater improvement from baseline in PASI (PASI 75) at 12 weeks. RESULTS: Five hundred and eighty-three subjects were randomized and received at least one dose of study drug. At week 12, a PASI 75 was achieved by 49% of patients in the etanercept 50 mg BIW group, 34% in the 25 mg BIW group, and 3% in the placebo group (P < 0.0001 for each etanercept group compared with placebo). At week 24 (after 12 weeks of open-label 25 mg etanercept BIW), a PASI 75 was achieved by 54% of patients whose dose was reduced from 50 mg BIW to 25 mg BIW, by 45% of patients in the continuous 25 mg BIW group, and by 28% in the group that received placebo followed by etanercept 25 mg BIW. Etanercept was well tolerated throughout the study. CONCLUSIONS: Etanercept provided clinically meaningful benefit to patients with chronic plaque psoriasis, with no apparent decrease in efficacy after dose reduction.     

Recommendations for the use of etanercept in psoriasis: a European dermatology expert group consensus

BACKGROUND: Psoriasis is a chronic, inflammatory skin disorder that has a significant impact on quality of life and, particularly in moderate to severe cases, adversely affects the patient's overall health and well-being. Biological treatments, such as etanercept, are being widely adopted across Europe for treatment of moderate to severe psoriasis due to favourable safety and efficacy profiles. The increase in usage, combined with a growing body of clinical evidence, has identified a need to clarify the best use of etanercept within its current treatment label. OBJECTIVE: To prepare a series of recommendations agreed by an expert group of dermatologists, relating to the most effective use of etanercept for psoriasis in Europe, within the product license. METHODS: An expert panel of dermatologists from across Europe completed a Delphi survey to address the current use of etanercept in psoriasis in Europe. In June 2005 the results were presented to the expert panel at their nominal group meeting, and a consensus was agreed. RESULTS: It was recommended that, where possible, patients are initiated on the 50 mg twice-weekly (BIW) dose. Etanercept should be given until remission is achieved (maximum 24 weeks) and retreatment should be initiated according to the physician's judgement. Before commencing treatment, contraindications, such as infection or previous malignancy (within 5 years), should be ruled out. CONCLUSIONS: The consensus presented herein provides valuable clarification of use of etanercept according to the label, which may have wider implications relating to the use of all biological therapies in psoriasis.     

Economic evaluation of etanercept in the management of chronic plaque psoriasis

Background  The National Institute for Health and Clinical Excellence has recommended that etanercept 25 mg twice weekly (biw) be used in adults with severe plaque psoriasis. However, its economic model did not consider the alternative licensed regimen of etanercept 50 mg biw.
Objectives  To assess the cost-effectiveness of etanercept 50 mg biw for the treatment of chronic plaque psoriasis, and to explore characteristics of patients who benefited most from 50 mg dosing.
Methods  An economic model was constructed to estimate the incremental cost per quality-adjusted life year (QALY) gained. The model considered patients with chronic plaque psoriasis who had both Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) of 10 or higher who were unable to take standard systemic therapies. Quality of life gain was estimated from the DLQI responses of patients enrolled in three clinical studies. The model considered expenditure on drugs, monitoring visits, adverse events and inpatient stays. Costs were estimated from the perspective of the U.K. National Health Service over a time period of 10 years.
Results  The incremental cost per QALY for etanercept 50 mg biw compared with no systemic therapy was found to be £6217 (95% confidence interval £5396–7486). The cost-effectiveness of 50 mg dosing was more attractive in patients with baseline PASI ≥ 20 (£5163) or baseline DLQI ≥ 20 (£4599).
Conclusions  This model found the licensed dose regimen of etanercept 50 mg biw to be cost effective in the U.K. This regimen was particularly appropriate for patients with severe disease or poor quality of life at baseline.     

阿维A治疗严重类型银屑病临床疗效观察

目的:评价阿维A治疗严重类型银屑病的临床疗效。方法:23例银屑病患者,应用阿维A治疗,成人阿维A初始剂量为0.75～1.00mg/(kg·d),平均维持剂量为10～30mg/d,平均疗程4～6周;儿童阿维A初始剂量为1.00mg/(kg·d),起效后维持量为0.10～0.20mg/(kg·d),最大不超过35.00mg/d。结果:在严重的寻常型斑块状银屑病、红皮病型银屑病、泛发性脓疱型银屑病中的有效率分别为87.5%、83.3%、100.0%。而关节病型银屑病有效率仅为50.0%。对皮肤干燥、口干、瘙痒、唇炎、掌跖脱屑以及血脂增高等不良反应进行了对症处理,结果均好转或消失。结论:阿维A治疗严重类型的银屑病疗效显著。     

Effects of etanercept on urine neopterin levels in patients with psoriasis in a controlled, open-label study

Neopterin is an immunological marker of cellular immune activation. Etanercept is a tumor necrosis factor-α (TNF-α) antagonist that decreases excessive levels of TNF-α associated with inflammatory disease down to physiological levels. The objective of this study was to investigate urine neopterin levels in psoriatic patients treated with etanercept, to study the effect of etanercept as a TNF-α blocker on urine neopterin levels. Urine neopterin levels and urine neopterin/creatinine ratios were measured by high-performance liquid chromatography in 22 patients with psoriasis before and after treatment with etanercept. Results were compared with a group of 20 healthy volunteers, and 20 patients with inflammatory skin diseases as control groups. Urine neopterin levels, neopterin/creatinine ratios and Psoriasis Area and Severity Index (PASI) scores were evaluated at baseline, and the 12th and 24th week after treatment. Urine neopterin levels were significantly elevated in the psoriatic group compared with control and inflammatory skin diseases groups ( P  < 0.05). Urine neopterin levels were significantly reduced after etanercept treatment. Statistically we did not find any correlation between neopterin levels and PASI scores. Our findings indicate that urine neopterin concentrations may reflect the disease activity in psoriasis, and may be used as a marker for monitoring disease activity and response to treatment with etanercept in psoriatic patients.     

Secukinumab and acitretin as a combination therapy for three clinical forms of severe psoriasis in multi‐drug refractory patients: A case series of high efficacy and safety profile

Secukinumab, the first monoclonal antibody that inhibits interleukin‐17A, has been shown to have rapid and long‐lasting efficacy in the treatment of moderate‐to‐severe psoriasis. However, there are still difficult‐to‐treat cases in which even dose‐escalation fails to provide a clinical response. In such cases, combining secukinumab with a conventional systemic agent may be a rational approach. Although methotrexate is most commonly preferred, acitretin may also be considered a good alternative, with its lower hepatotoxic potential. Data are limited regarding the use of combination therapy of secukinumab and acitretin for psoriasis. We herein present three patients with chronic plaque, generalized pustular and erythrodermic psoriasis, respectively, accompanied by multiple comorbidities, in whom skin clearance could not be achieved with several conventional and biologic therapies (including escalated dose regimens of secukinumab in two patients). Alternatively, we used a combination of secukinumab with low‐dose acitretin, which resulted in a complete or almost complete skin clearance in all patients, with no adverse events or increased toxicity. Based on our real‐life clinical experience with those patients, acitretin seems an effective and safe option to be used in combination with secukinumab. Even in patients who are refractory to multiple drugs including escalated doses of secukinumab, the addition of low‐dose acitretin may be helpful in achieving treatment goals, decreasing the need for switching to another biologic therapy.     

Comparison of cutaneous tolerance and efficacy of calcitriol 3 microg g(-1) ointment and tacrolimus 0.3 mg g(-1) ointment in chronic plaque psoriasis involving facial or genitofemoral areas: a double-blind, randomized controlled trial

BACKGROUND: Two nonsteroidal topical agents, calcitriol and tacrolimus, have been reported to be effective and safe for psoriatic lesions on sensitive areas. However, no comparative studies between calcitriol and tacrolimus have been reported. OBJECTIVES: To compare the tolerability and efficacy of calcitriol 3 microg g(-1) and tacrolimus 0.3 mg g(-1) ointment in chronic plaque psoriasis affecting facial and genitofemoral regions. METHODS: This is a double-blind, parallel, 6-week study of 50 patients who were randomized in a 1 : 1 ratio to apply calcitriol or tacrolimus twice daily. The primary efficacy variable was the mean reduction of the target area score (TAS), and the secondary efficacy variable was the percentage of patients with the Physician's Global Assessment (PGA) score of 5 (clear) and 4 (almost clear) at the end of the study. RESULTS: Both calcitriol and tacrolimus were well tolerated. Although calcitriol induced perilesional erythema in a statistically significant higher proportion of patients than tacrolimus (55% vs. 16% at week 6; P < 0.05), it did not necessitate treatment discontinuation. At the end of the study, tacrolimus was significantly more effective than calcitriol based on a significant reduction of mean TAS (67% vs. 51%; P < 0.05) as well as more patients achieving complete or almost complete clearance by PGA (60% vs. 33%; P < 0.05). CONCLUSIONS: Both calcitriol 3 microg g(-1) and tacrolimus 0.3 mg g(-1) are safe and well-tolerated therapeutic agents in the treatment of psoriasis in sensitive areas. Tacrolimus demonstrated a more effective clinical outcome compared with calcitriol.     

Tofacitinib for the treatment of moderate to severe chronic plaque psoriasis in Japanese patients: Subgroup analyses from a randomized,placebo‐controlled phase 3 trial

Tofacitinib is an oral Janus kinase inhibitor. These post‐hoc analyses assessed tofacitinib efficacy and safety in Japanese patients with psoriasis enrolled in a 52‐week global phase 3 study. Patients received tofacitinib 5 mg, tofacitinib 10 mg or placebo twice daily (b.i.d.); placebo‐treated patients advanced to tofacitinib at week 16. Primary efficacy end‐points were the proportions of patients with 75% or more reduction from baseline Psoriasis Area and Severity Index (PASI‐75) and Physician's Global Assessment (PGA) of “clear” or “almost clear” (PGA response) at week 16. Other end‐points included: Itch Severity Item (ISI), Dermatology Life Quality Index (DLQI) score and Nail Psoriasis Severity Index (NAPSI). Adverse events (AEs) were recorded throughout the study. Overall, 58 Japanese patients were included in this analysis (tofacitinib 5 mg b.i.d., n = 22; 10 mg b.i.d., n = 24; placebo, n = 12); 29 completed the study. At week 16, significantly more patients receiving tofacitinib 5 and 10 mg b.i.d. versus placebo achieved PASI‐75 (50% and 75% vs 0%, P < 0.01) and PGA response (59% and 75% vs 0%, P < 0.001). Substantial improvements in ISI, DLQI and NAPSI score were observed with both tofacitinib doses. Over 52 weeks, similar rates of AEs were reported across treatment groups; one serious AE occurred with tofacitinib 10 mg b.i.d. Herpes zoster occurred in three patients receiving tofacitinib 10 mg b.i.d. No deaths, serious infections, malignancies or gastrointestinal perforations were reported. Results were generally consistent with global analysis, suggesting sustained efficacy and a manageable safety profile, with increased herpes zoster incidence, of tofacitinib in Japanese patients with psoriasis.     

Sequential treatment with biologics: switching from efalizumab to etanercept in 35 patients with high‐need psoriasis

Background Use of biological agents has been shown to be an efficacious approach in psoriasis, when traditional treatments fail. However, there are limited data on the effectiveness and safety of switching from one biological agent to another. Objectives We aimed to evaluate the effectiveness and safety of etanercept as a sequential treatment in patients previously treated with efalizumab, and to evaluate different transition strategies from efalizumab to etanercept. Methods We present a retrospective study in patients with high‐need plaque psoriasis who were unable to continue efalizumab and were immediately switched to etanercept. Results We included 35 patients during a 4.5‐year period. At 24 weeks of etanercept therapy, 57% of patients had a PASI reduction of 75%, suggesting that alternating between biological agents is feasible. We used three different switching approaches: (i) etanercept in combination with cyclosporine as bridge therapy, (ii) etanercept in combination with methotrexate as bridge therapy, (iii) etanercept monotherapy. Combination therapy was efficacious in all patients, including eight patients with rebound phenomenon with efalizumab. Etanercept was discontinued in two patients as a result of serious adverse events that consisted of an oral squamous cell carcinoma and a diffuse B‐cell‐non‐Hodgkin lymphoma. Conclusions In our experience, it seems that etanercept alone may not be sufficient when transitioning from efalizumab in high‐need patients with severe worsening or rebound of psoriasis. In such patients, combination of etanercept with cyclosporine or methotrexate is a more effective approach. Non‐response to efalizumab did not preclude clinical response after switching to etanercept.     

A systematic review of antistreptococcal interventions for guttate and chronic plaque psoriasis

BACKGROUND: Guttate psoriasis is closely associated with preceding or concurrent streptococcal infection. Some authorities have claimed that chronic plaque psoriasis may also be made worse by infection. In view of this many dermatologists have recommended using antibiotics for psoriasis, particularly guttate type. Some dermatologists have also recommended tonsillectomy for psoriasis in patients with recurrent streptococcal pharyngitis. OBJECTIVES: This review aims to assess the evidence for the effectiveness of antistreptococcal interventions, including antibiotics and tonsillectomy in the management of acute guttate and chronic plaque psoriasis. METHODS: Studies were identified by searching the Cochrane Clinical Trials Register (Cochrane Library, Issue 3, 1999), Medline (1966-September 1999), Embase (1988-September 1999), the Salford Database of Psoriasis Trials (to November 1999) and the European Dermato-Epidemiology Network (EDEN) Psoriasis Trials Database (to November 1999) for terms (STREPTOCOCC* or ANTIBIOTIC* or TONSIL*) and PSORIASIS using the Cochrane Skin Group search strategy. RESULTS: Only one trial met the selection criteria. This compared the use of two oral antibiotic schedules in 20 psoriasis patients, predominantly of guttate type, who had evidence of beta-haemolytic streptococcal colonization. Either rifampicin or placebo was added to the end of a standard course of phenoxymethylpenicillin or erythromycin. No patient in either arm of the study improved during the observation period. No randomized trials of tonsillectomy for psoriasis were identified. CONCLUSIONS: Although both antibiotics and tonsillectomy have frequently been advocated both for patients with guttate psoriasis and for selected patients with chronic plaque psoriasis, there is to date no good evidence that either intervention is beneficial.     

Reconsideration of 2008 decision: Food and Drug Administration approval of etanercept for systemic treatment of moderate to severe pediatric psoriasis

Although systemic etanercept was approved in 2004 for adults, the Food and Drug Administration (FDA) denied approval for use in children with psoriasis in 2008. Revision of the FDA's risk‐benefit assessment in response to understanding of disease burden, unmet medical need, and the effect of off‐label use in children with psoriasis led to the 2016 approval as the first systemic biologic product for the treatment of children aged 4‐17 with moderate to severe psoriasis. This article delineates the thinking that led to this reconsideration. The underlying thinking paved the way to inform current pediatric drug development as the FDA continues to bring needed medical products to children.     

Manifestation of Crohn's disease in a young woman during the course of treatment for severe form of chronic plaque psoriasis with etanercept

With the growing number of patients with immune‐modulated diseases treated with tumor necrosis factor (TNF) alpha inhibitors, we are more frequently encountering the occurrence of so‐called paradoxical drug reactions. These are basically situations where during the course of the treatment of one disease, the manifestation of another with similar etiopathogenesis occurs, although under normal conditions this newly developed disease responds well to treatment with TNF alpha inhibitors and is indicated for this treatment. Skin reactions are most frequently recorded in the form of induced psoriasis and psoriasiform exanthems. A less common paradoxical reaction is the induction of Crohn's disease, which is most often described in association with the treatment of inflammatory joint diseases with etanercept. We present a case of induction of Crohn's disease during therapy with etanercept, where the primary disease being treated was psoriasis. In the literature, similar cases have only been described sporadically.     

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.     

Adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis: Efficacy and safety results from a Phase II/III randomized controlled study

Incidence of psoriasis vulgaris in Asians is estimated at 0.05–0.3%. Studies in North America and Europe demonstrated that adalimumab, a fully human, recombinant, immunoglobulin G₁ monoclonal antibody, was efficacious and well‐tolerated in patients with chronic plaque psoriasis. This 24‐week, placebo‐controlled study evaluated the efficacy and safety of three different dosing regimens of adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis (n = 169). Patients were randomized to receive adalimumab 40 mg every other week (eow), adalimumab 80‐mg loading dose at week 0 followed by adalimumab 40 mg eow starting at week 2, adalimumab 80 mg eow, or placebo eow given as s.c. injections. The primary efficacy endpoint was the percentage of patients achieving a 75% or greater improvement in Psoriasis Area and Severity Index (PASI 75) score at week 16. At week 16, PASI 75 response rates were significantly greater for all three adalimumab groups (40 mg eow: 57.9%, P < 0.001; 40 mg eow plus loading dose: 62.8%, P < 0.001; 80 mg eow: 81.0%, P < 0.001) versus placebo (4.3%). As early as week 4, the 40‐mg eow plus loading dose and 80‐mg eow groups achieved significantly greater PASI 75 response rates compared with placebo. Injection‐site reactions and hepatic events occurred in greater percentages of adalimumab‐treated patients compared with placebo. Adalimumab therapy demonstrated efficacy and safety at all three dosage regimens. Rapid response rate in patients receiving 40 mg eow plus loading dose supports using an 80‐mg loading dose in the treatment of psoriasis.