Switching from etanercept to adalimumab is effective and safe: results in 30 patients with psoriasis with primary failure,secondary failure or intolerance to etanercept

Background Knowledge on the sequential treatment of psoriasis with biologics with regard to efficacy and safety is sparse. This also applies to the efficacy and safety of adalimumab in patients previously treated with etanercept. The relationship between the reasons for discontinuation of etanercept and the response to adalimumab is not clear in psoriasis. Objectives To evaluate the efficacy and safety of adalimumab in patients with psoriasis with primary failure, secondary failure or intolerance to etanercept in daily practice. Methods Data were extracted from two prospective registries from all patients with psoriasis with failure on etanercept treatment, who switched to adalimumab therapy. Thirty patients fulfilled these criteria. All patients were naive to biologics when etanercept was initiated. Primary endpoints were the percentage of patients achieving a 50% or 75% improvement of the baseline Psoriasis Area and Severity Index (PASI) score (PASI 50 and PASI 75, respectively) at weeks 12, 24 and 48. Secondary endpoints were the percentage of patients achieving PASI 90, the mean percentage improvement in the PASI score from baseline and the adverse event rate. Results Compared with the baseline PASI score before the start of etanercept, the mean percentage improvement in PASI and the PASI 50/75/90 response rates to adalimumab until week 48 were comparable to those achieved with etanercept. In the patients failing on etanercept, PASI 75 was achieved by 27%, 36% and 54% at weeks 12, 24 and 48 of adalimumab treatment, respectively. The majority of patients showed a beneficial response to adalimumab, irrespective of the reason for discontinuation of etanercept. Previous treatment with etanercept did not increase the adverse event rate nor change the nature of the side‐effects. Conclusions Adalimumab seems to be an effective and safe treatment option for patients with psoriasis who failed on etanercept treatment irrespective of the reason for discontinuation.     

Treatment with 311-nm ultraviolet B accelerates and improves the clearance of psoriatic lesions in patients treated with etanercept

Background  Some patients with plaque-type psoriasis respond slowly to treatment with etanercept. In such cases combining etanercept with conventional treatments might be helpful.
Objectives  To investigate whether treatment with 311-nm ultraviolet (UV) B can improve the therapeutic response in patients treated with etanercept.
Methods  Four women and one man (mean age 57 years, range 48–66) with moderate to severe plaque-type psoriasis who had received standard treatment with etanercept 50 mg twice weekly for 6 weeks without Psoriasis Area and Severity Index (PASI) reduction of 75% or greater (of initial mean PASI of 16·0, range 15·4–20·4) were enrolled in the study. Starting at 6 weeks, 311-nm UVB treatment was given to a randomly selected body half (left or right, excluding the head) for another 6 weeks, while all patients continued receiving etanercept. The patients were monitored by half-body PASI at weekly intervals.
Results  During the 6-week irradiation regimen, 311-nm UVB significantly bolstered the therapeutic response in the patients on etanercept treatment. After 6 weeks of 311-nm UVB, the patients had a mean PASI on their UV-irradiated body halves of 1·6 (range 0·6–3·3) vs. 4·7 (range 1·4–8·6) on nonirradiated body halves ( P  =   0·0192, paired two-tailed t -test), compared with 10·7 (range 6–16·4) and 10·5 (range 5·2–16·4) at start of 311-nm UVB treatment. The overall mean PASI reduction from baseline (i.e. at etanercept start) was 89% vs. 68%, respectively ( P  =   0·0009 and P  =   0·0088).
Conclusions  Treatment with 311-nm UVB significantly accelerates and improves the clearance of psoriatic lesions in patients responding slowly to etanercept monotherapy.     

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.     

Etanercept: Efficacy and safety

Objective  To evaluate the efficacy and safety of etanercept in the treatment of patients with moderate to severe plaque psoriasis.
Methods  An observational, longitudinal, and retrospective study involving two groups of dose of treatment with etanercept (50 vs. 100 mg/week). The selected patients presented moderate to severe plaque psoriasis, and they had received treatment with the mentioned drug. A total of 58 patients were included in the study. The efficacy of the drug was evaluated by measuring the psoriasis area and severity index (PASI), body surface area (BSA) and physician's global assessment (PGA) in weeks 8, 16, 24, 32, 40 and 48.
Results  A statistically significant improvement was observed in the PASI, BSA and PGA indexes after 24 and 48 weeks of therapy. As for PASI, and after 48 weeks of treatment, PASI 50, 75 and 90 were 100.0%, 92.3% and 69.2%, respectively. In our series, etanercept 50 mg/week reached the same results after 48 weeks as etanercept 100 mg/week, though the initial response was faster in the last group. The PASI, BSA and PGA indexes diminished significantly with the treatment, though without statistically significant differences between both groups. As for the safety, etanercept was well tolerated, and no serious adverse events were recorded. There were no cases of tuberculosis or opportunistic infections.
Conclusions  Our study confirms the efficacy and safety outcomes of the clinical trials of etanercept in psoriasis with both doses of treatment. As for the safety, etanercept was well tolerated, and all the recorded adverse events coincided with the known potential side-effects of treatment.

Conflicts of interest

None declared     

Adalimumab treatment for severe recalcitrant chronic plaque psoriasis

Aim.  To assess the efficacy and safety profile of adalimumab in patients with severe, recalcitrant chronic plaque psoriasis, and to assess short-term overlapping of other systemic treatment with adalimumab to prevent flaring of disease.
Methods.  This was a retrospective study comprising 39 patients with chronic plaque psoriasis treated with adalimumab between October 2005 and January 2008. All had failed treatment with other systemic agents, including biological therapies in 59% of patients. Patients were started on adalimumab 40 mg weekly or fortnightly, as clinically indicated. Severity of psoriasis was assessed by the Psoriasis Area and Severity Index (PASI). Therapeutic response was assessed by 75% improvement on PASI (PASI 75). All adverse events were recorded.
Results.  Results were analysed separately for those treated with adalimumab only and those on combination treatment. PASI 75 was achieved in 38% (8 of 21 patients at week 16), 62% (13 of 21 patients) at week 24, 69% (9 of 13 patients) at week 48% and 71% (5 of 7 patients) at week 72 in the adalimumab-only group, compared with 56% (5 of 9 patients) at week 16, 50% (4 of 8 patients) at week 24, 80% (4 of 5 patients) at week 48% and 67% (2 of 3 patients) at week 72 in the combined group. Of the 39 patients, 15 (38%) achieved a PASI of 0 at some point in their treatment. Adalimumab was well tolerated; 38% of patients experienced side-effects, which were generally mild.
Conclusion.  Adalimumab was effective in a group of patients with psoriasis refractory to other systemic therapies, including biological treatments, and was well tolerated.     

Comparison of clinical and pharmacokinetic profiles of etanercept 25 mg twice weekly and 50 mg once weekly in patients with psoriasis

BACKGROUND: Etanercept is a tumour necrosis factor antagonist that is approved in the U.S.A., Canada and Europe for treating adult patients with chronic moderate to severe plaque psoriasis. OBJECTIVES: To assess whether clinical efficacy, safety and pharmacokinetic (PK) profiles of etanercept 50 mg once weekly are comparable to etanercept 25 mg twice weekly. METHODS: Patients from a U.S. phase 3 study and a global phase 3 study were subsequently enrolled in an open-label extension study (extension study) where they all received etanercept at a dose of 50 mg once weekly for an initial 12 weeks. Patients who had received at least 24 weeks of etanercept 25 mg twice weekly in the global phase 3 study and were enrolled in the extension study (n = 265) were assessed for efficacy and safety at extension study baseline and after 12 weeks of etanercept 50 mg once weekly. Efficacy endpoints included the Psoriasis Area and Severity Index (PASI), the Dermatology Life Quality Index and the Physician's Global Assessment of psoriasis. In addition, PK profiles from patients in the U.S. phase 3 study were compared with PK profiles from another set of patients in the extension study. Comparison was made between a subset of patients receiving etanercept 25 mg twice weekly dosing in the U.S. phase 3 study (n = 13) and those receiving etanercept 50 mg once weekly in the extension study (n = 84). RESULTS: The mean PASI score was 5.77 at extension study baseline after treatment with etanercept 25 mg twice weekly, which was sustained at 5.82 after 12 weeks of etanercept 50 mg once weekly. Similar results were observed in other efficacy endpoints. Etanercept 50 mg once weekly was generally well tolerated. No new safety findings were reported. PK profiles overlapped extensively between the two dosing regimens. CONCLUSIONS: In this report, we demonstrate that efficacy, safety and PK profiles were comparable between etanercept 25 mg twice weekly and 50 mg once weekly in patients who had received at least 24 weeks of etanercept 25 mg twice weekly prior to receiving etanercept 50 mg once weekly in the extension study.     

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.     

Combined treatment with etanercept 50 mg once weekly and narrow-band ultraviolet B phototherapy in chronic plaque psoriasis

The combination of etanercept, a tumour necrosis factor α inhibitor, with narrow-band ultraviolet B (NB-UVB) phototherapy has recently been reported to be effective in moderate-to-severe plaque psoriasis, yielding better results than either monotherapy. To assess the efficacy and safety of this combined treatment using the lower approved etanercept dosage. In this single-arm open-label study patients received etanercept 50 mg once weekly combined with NB-UVB phototherapy three times weekly for 8 weeks, followed by etanercept alone until week 12. We evaluated the proportion of patients achieving 75%, 90% and 100% improvement of their initial PASI score (PASI75, PASI90, and PASI100, respectively). Patients were 19 men and 14 women, mean age 48.3 years ± 12.1 standard deviation (SD) and mean baseline Psoriasis Area and Severity Index (PASI) score 22.5 ± 7.5. On treatment weeks 4, 8, and 12, 24.2%, 66.7%, and 81.8% of patients achieved PASI75; 8.0%, 15.1%, and 57.6% reached PASI90, and 0%, 6.0%, and 24.2% attained PASI100, respectively. There were no severe side effects. Low-dosage etanercept combined with NB-UVB phototherapy is an effective, safe and economical approach to treat moderate-to-severe plaque psoriasis. Further studies are clearly required to assess its long-term efficacy and safety.     

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.     

Efficacy and Safety of Etanercept in Psoriasis after Switching from Other Treatments

Background: Since targeted biologic treatments have been introduced for the treatment of plaque-type psoriasis and psoriatic arthritis, switching between different medications has become necessary in selected patients, particularly after treatment failures. Objective: To evaluate the efficacy and safety of etanercept treatment in adult patients with psoriasis after failure to respond to other previous therapies. In particular, the differences in efficacy profiles after switching from traditional (cyclosporine [ciclosporin], methotrexate, retinoids, fumaric acid esters, psoralen plus UVA therapy, corticosteroids) or biologic (infliximab, efalizumab) treatments were analyzed. Methods: The study included 124 patients affected by plaque-type psoriasis who received etanercept administered subcutaneously at a dosage of 50 mg twice weekly for 12 weeks, followed by 25 mg twice weekly for an additional 12 weeks, and 110 patients affected by psoriatic arthritis who were treated with etanercept 25 mg twice weekly in a continuous regimen, after a 12-week period of treatment with etanercept 50 mg twice weekly. Results: Efficacy results were consistent in both groups of patients (plaque-type psoriasis and psoriatic arthritis), as expressed by the percentage of patients who achieved Psoriasis Area and Severity Index (PASI) 50 and PASI 75 scores. Among psoriatic arthritis patients, the mean pain Visual Analog Scale (VAS) score showed a substantial reduction during the treatment course, from 67.2 at week 0 to 15.8 at week 24. After 24 weeks, among patients with plaque-type psoriasis who had not previously received biologic therapies, 89.9% of patients achieved PASI 50 and 75.3% achieved PASI 75, while among patients who had received biologic therapies, 69.6% of patients achieved PASI 50 and 65.2% achieved PASI 75. In addition, 92.3% of patients with psoriatic arthritis who had not previously received biologic therapies achieved PASI 50 and 73.8% achieved PASI 75, while among patients who had received biologic therapies, 45.8% of patients achieved PASI 50 and 29.2% achieved PASI 75. Conclusions: Our study demonstrated that etanercept was more effective in those patients who had not previously received other biologic therapies than in those who had. The results of the present study indicate that etanercept may represent a valid, effective, and well tolerated therapeutic alternative even after failure to respond to traditional and other biologic therapies.     

Clinical effectiveness and safety experience with alefacept in the treatment of patients with moderate-to-severe chronic plaque psoriasis in Taiwan: results of an open-label, single-arm, multicentre pilot study

Background  The effectiveness and safety of alefacept for the treatment of moderate-to-severe chronic plaque psoriasis has been established in several clinical trials conducted in the United States and Europe. No clinical trial of alefacept has been conducted in Asia.
Objective  To determine the effectiveness and safety of alefacept in the treatment of psoriasis in Chinese population.
Design and methods  This was an open-label, single-arm, multicentre pilot study conducted at three centres. Patients with a body surface area ≥ 10% and psoriasis area and severity Index (PASI) ≥ 12 were given 15 mg alefacept intramuscularly once a week for 12 weeks and were then followed up for a further 12 weeks.
Results  A total of 46 patients was enrolled. Only one subject (2%) achieved a ≥ 75% improvement in PASI at week 14. The median improvement in PASI at week 14 after the 12-week treatment was 39%. At any time during the 6-month course, 3 subjects (7%) achieved a Physician Global Assessment (PGA) of 'almost clear', and a ≥ 50% and ≥ 75% improvement in PASI was seen in 46% and 9%, respectively. There is a trend for decreased counts of CD4⁺ and CD8⁺ cells after alefacept treatment, but subjects who achieved PASI50 showed a lesser degree of decrease in CD4⁺ and CD8⁺ counts compared with those in patients who did not achieve PASI50.
Conclusions  This small pilot study indicated that intramuscular alefacept was effective and safe in psoriasis in Chinese patients over 12 weeks of treatment. Further studies are needed to clarify the reason for low PASI 75 effectiveness and the paradoxical lesser decline of CD4⁺ and CD8⁺ T cells in those who responded.     

Etanercept use for psoriasis in Taiwan: a case series study

Background The reported efficacy and safety of some biologic agents for psoriasis vary between Caucasians and Asians. Few reports of etanercept exist in psoriasis patients within the Asia‐Pacific region. Objectives The study aims to report our clinical experience of etanercept in the treatment of patients with moderate‐to‐severe psoriasis in Taiwan. Methods A retrospective analysis of 59 patients with moderate‐to‐severe psoriasis who received etanercept was conducted in a tertiary referral center. Results Etanercept therapy resulted in a reduction of mean Psoriasis Area and Severity Index (PASI) of 47% at week 12 and 61% at week 24. After 12 weeks of treatment, 48%, 26%, and 3.4% of the patients achieved at least PASI50, 75 and 90 response, respectively. At week 24, the proportion of patients achieving at least PASI50, 75 and 90 response was 59%, 37%, and 14%, respectively. Etanercept efficacy in achieving PASI75 improvement was, however, lower than that reported in previous pivotal placebo‐controlled trials. No cases of active tuberculosis, viral hepatitis or malignancies were observed during the observation period. Conclusion Our case series demonstrated the efficacy and safety of etanercept for the management of moderate‐to‐severe psoriasis in Taiwan.     

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.     

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.     

Chronic hand eczema - self-management and prognosis: a study protocol for a randomised clinical trial

Background

The purpose of this study was to estimate the annual and per-patient budget impact of the treatment of moderate to severe psoriasis in Greece before and after the introduction of ustekinumab.

Methods

A budget impact model was constructed from a national health system perspective to depict the clinical and economic aspects of psoriasis treatment over 5?years. The model included drug acquisition, monitoring, and administration costs for both the induction and maintenance years for patients in a treatment mix with etanercept, adalimumab, infliximab, with or without ustekinumab. It also considered the resource utilization for non-responders. Greek treatment patterns and resource utilization data were derived from 110 interviews with dermatologists conducted in February 2009 and evaluated by an expert panel of 18 key opinion leaders. Officially published sources were used to derive the unit costs. Costs of adverse events and indirect costs were excluded from the analysis. Treatment response was defined as the probability of achieving a PASI 50, PASI 75, or PASI 90 response, based on published clinical trial data.

Results

The inclusion of ustekinumab in the biological treatment mix for moderate to severe psoriasis is predicted to lead to total per-patient savings of ?443 and ?900 in years 1 and 5 of its introduction, respectively. The cost savings were attributed to reduced administration costs, reduced hospitalizations for non-responders, and improved efficacy. These results were mainly driven by the low number of administrations required with ustekinumab over a 5?year treatment period (22 for ustekinumab, compared with 272 for etanercept, 131 for adalimumab, and 36 for infliximab).

Conclusions

The inclusion of ustekinumab in the treatment of moderate to severe psoriasis in Greece is anticipated to have short- and long-term health and economic benefits, both on an annual and per-patient basis.     

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。     

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.     

Adalimumab for psoriasis in Greece: clinical experience in a tertiary referral centre

Background Adalimumab, a fully human, anti‐TNFα monoclonal antibody has been shown to be effective for moderate‐to‐severe psoriasis in clinical trial setting. However, only a limited number of studies reflect everyday clinical experience with this drug. Objectives To provide evidence on the efficacy, dose optimization and safety of adalimumab based on everyday clinical experience in a tertiary referral centre for psoriasis, in Greece. Methods We retrospectively reviewed the records of all patients with moderate‐to‐severe psoriasis who received adalimumab, in our referral centre, between January 2008 and October 2010. Results In total, 52 patients were treated with adalimumab for a mean period of 14 months (range 4–30 months). Mean baseline Psoriasis Area and Severity Index (PASI) was 16.7 (range 9–40.3). At 4, 6, 12 and 18 months, PASI75 was attained by 68%, 82%, 89% and 88% of patients respectively. Nineteen of 52 patients (36%) reached a PASI100 at a mean time of 10 months (range 4–18 months). The dose interval between the injections of adalimumab was increased from 2 to 3 weeks for 14 patients (27%) who achieved and sustained a PASI100 after the first year of treatment, without any relapse. The overall rate of adverse events reached 38%, but treatment was discontinued only in two cases (4%). Conclusions Our study demonstrates that adalimumab is effective and safe in patients with moderate‐to‐severe psoriasis in short‐ and long‐term setting. At the same time, it points out novel and interesting issues for further investigation.     

Efficacy, safety and medication cost implications of adalimumab 40 mg weekly dosing in patients with psoriasis with suboptimal response to 40 mg every other week dosing: results from an open-label study

Background The clinical utility of increasing to weekly adalimumab therapy in patients with psoriasis with inadequate response to every other week (eow) dosing is unknown. Objectives (i) To determine the effectiveness of escalating adalimumab dosage from 40 mg eow to 40 mg weekly in patients with < PASI 50 response following ≥ 24 weeks treatment. (ii) To identify retrospectively characteristics of patients likely to benefit from dose escalation using classification and regression tree analysis. (iii) To assess cost implications for allowing dose escalation from the private payers’ perspective. Methods Patients with moderate‐to‐severe psoriasis who had received blinded adalimumab 40 mg eow or placebo in antecedent phase II/III studies could enrol in an open‐label extension (OLE) and initially receive open‐label adalimumab 40 mg eow (EOW population). On/after week 24 (OLE), patients with < PASI 50 response relative to baseline of antecedent study could increase to 40 mg weekly. The dosage escalation population continued on weekly dosing until achieving PASI 75 response, then resumed eow dosing. Study visits were 6/12 weeks after dosage escalation, and every 12 weeks thereafter. The percentage of patients who achieved PASI 75 response following dosage escalation was determined (missing PASI scores imputed as nonresponse). Safety was assessed for the dosage escalation population and for all adalimumab exposure that did not follow dosage escalation in the EOW set. Results In total, 349/1256 (27·8%) patients underwent dosage escalation (OLE). At 12/24 weeks after dosage escalation, 93/349 (26·6%)/133/349 (38·1%) were PASI 75 responders or resumed eow dosing. Secondary nonresponders, patients weighing ≤ 102 kg, and those with disease duration < 8·3 years were most likely to benefit from dose escalation. Rates of serious/serious infectious/malignant (excluding nonmelanoma skin cancers or lymphoma) adverse events were 6·8/0·9/1·4 events per 100 patient‐years (dosage escalation population); comparable rates in the EOW set were 6·5/1·2/0·5 events per 100 patient‐years. Conclusions Most patients did not require dose escalation. By 12 weeks after dose escalation, one‐quarter achieved substantial clinical improvement. Safety results were similar between patients who dosage‐escalated and those who did not.     

Treatment of erythrodermic psoriasis with etanercept

BACKGROUND: Severe variants of psoriasis, such as erythrodermic psoriasis, may be associated with serious morbidity and mortality. Current treatment options for erythrodermic psoriasis are limited, unsatisfactory and potentially associated with organ-specific toxicity. Recently, a new class of agents, targeted biological therapies, has emerged. Etanercept is a recombinant human fusion protein acting as a competitive inhibitor of tumour necrosis factor-alpha. The safety and efficacy of etanercept have been widely demonstrated in psoriatic arthritis and moderate to severe plaque-type psoriasis. OBJECTIVES: To assess the efficacy and tolerability of etanercept in the treatment of erythrodermic psoriasis over a period of 24 weeks. METHODS: Ten patients, eight men and two women, were selected to receive etanercept 25 mg subcutaneously twice weekly. The Psoriasis Area and Severity Index (PASI) score, ranging from 0 to 72, was used to assess the severity of disease. RESULTS: Etanercept was well tolerated and led to a significant reduction in the severity of disease over the period of treatment. After 24 weeks, the mean PASI score decreased from 39.1 (baseline) to 5.1. At week 12, five of 10 (50%) patients achieved an improvement of PASI score from baseline exceeding 75%. At week 24, six of 10 patients (60%) achieved or maintained an improvement of PASI score from baseline exceeding 75% while two patients (20%) maintained an improvement of between 50% and 75%. CONCLUSIONS: In this study, etanercept has been demonstrated to be an effective treatment for erythrodermic psoriasis, providing a safe and convenient alternative to current therapies.