Efficacy of infliximab for severe recalcitrant psoriasis after 6 weeks of treatment

Infliximab treatment has been shown to be effective for moderate-to-severe psoriasis in several large clinical trials. Nonetheless, experience with this new treatment is still needed to evaluate its efficacy and tolerance in everyday practice. In this follow-up study, we report our experience with infliximab for recalcitrant psoriasis. Nineteen patients with recalcitrant psoriasis were treated between July 2004 and December 2006 with 5 mg/kg infliximab i.v. at weeks 0, 2 and 6 followed by maintenance every 8 weeks. In three patients resistant to treatment, methotrexate was added at a 15-25 mg dose weekly after the sixth week of infliximab therapy. Pretreatment evaluations included chest X-ray, tuberculin test (5 units), full blood count, kidney and liver function tests, antinuclear antibodies and patient weight. Response to treatment, using the Psoriasis Area and Severity Index (PASI) score, and adverse effects were prospectively assessed at weeks 0, 6 and 22. At week 6, after only two infusions, 78.9% (15/19) of patients showed at least 75% improvement in baseline PASI (PASI 75). At week 22, 73.6% (14/19) patients had reached PASI 75. Three patients had a relapse. Four developed adverse effects that required suspension of infliximab therapy. No tuberculosis or lymphoproliferative disease was observed. Four patients (21%) showed apparition of positive antinuclear antibody during the course of treatment and 57.8% (11/19) of patients showed an increase in weight at week 22. Our experience shows that infliximab is a very rapidly effective treatment of severe, treatment-resistant psoriasis as soon as the sixth week of treatment.     

Infliximab improves health-related quality of life in the presence of comorbidities among patients with moderate-to-severe psoriasis

Background  Psoriasis affects patients both physically and psychologically.
Objectives  To investigate the effect of comorbidities on health-related quality of life (HRQoL) and to determine whether infliximab improved HRQoL in the presence of these conditions.
Methods  In this multicentre, double-blind study, 835 patients with moderate-to-severe plaque psoriasis were randomized to receive infliximab 3 or 5 mg kg⁻¹ or placebo at weeks 0, 2 and 6. Infliximab-treated patients were re-randomized at week 14 to receive the same treatment every 8 weeks or as needed through week 46; placebo patients crossed over to infliximab 5 mg kg⁻¹ at week 16. Disease severity (Psoriasis Area and Severity Index, PASI) and HRQoL (Dermatology Life Quality Index, DLQI; 36-item Short-Form Health Survey, SF-36) were measured at various time points. The effect of patient comorbidities on baseline HRQoL was assessed using multiple regression models. The impact of key comorbidities on infliximab treatment effect was also assessed.
Results  Disease severity (PASI), depression and psoriatic arthritis (PsA) were predictors of poor baseline HRQoL. At week 10, infliximab 3 and 5 mg kg⁻¹ significantly improved physical and mental health dimensions of the SF-36 and the DLQI (all P  < 0·001). Consistent improvement in HRQoL with infliximab treatment was observed regardless of baseline patient characteristics or comorbidities. Through week 50, HRQoL and PASI scores were most improved with infliximab 5 mg kg⁻¹ administered every 8 weeks.
Conclusions  Disease severity, depression and PsA were significant predictors of poor HRQoL. Infliximab significantly improved HRQoL, regardless of these characteristics.     

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.     

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.     

Etanercept combined with methotrexate for high-need psoriasis

Background  For some high-need psoriatic patients, the efficacy of etanercept monotherapy is insufficient. In these cases it might be indicated to combine etanercept with other conventional treatments.
Objectives  To provide daily practice safety and efficacy data for etanercept and methotrexate combination therapy.
Methods  Data were extracted from an existing database, which contains prospective safety and efficacy data of all patients who were treated with etanercept in clinical practice. A case was defined as a patient using etanercept and methotrexate simultaneously for an indefinite period during follow-up. For all cases, baseline data, Psoriasis Area and Severity Index (PASI) scores, adverse events and laboratory values were investigated. Furthermore, the influence of introduction and discontinuation of methotrexate on these parameters was analysed.
Results  Fourteen patients with simultaneous use of etanercept and methotrexate were selected. In six patients, methotrexate was introduced after etanercept to avoid further psoriasis deterioration, which resulted in an improvement of psoriasis in four of these patients. Eight patients were on methotrexate therapy before start of etanercept. Discontinuation of methotrexate in six of these patients resulted in a decrease in PASI improvement in five patients. Etanercept combined with methotrexate was well tolerated, and only mild adverse events were reported. No clinically significant changes in laboratory parameters occurred.
Conclusions  Results show that combining etanercept with methotrexate is reasonable when efficacy of etanercept monotherapy is insufficient, or when rapid deterioration of psoriasis after abrupt discontinuation of methotrexate is expected. Laboratory values and adverse events were not different from what would have been expected when using methotrexate alone.     

Five‐year experience with infliximab: Follow up of the product familiarisation program

This 5‐year retrospective analysis is of 22 patients who participated in the product familiarisation program (PFP) at St Vincent's Hospital Melbourne, prior to the listing of infliximab on the Pharmaceutical Benefit Scheme. Criteria for inclusion were being an adult with chronic plaque psoriasis, having a psoriasis area and severity index (PASI) score of at least 15 with an inadequate response or intolerance to three of the following: phototherapy, acitretin, cyclosporin and methotrexate. Participants were infused with infliximab 5 mg/kg on the standard induction (weeks 0, 2 and 6) and maintenance (8‐weekly) protocols. At each visit PASI and dermatology life quality index (DLQI) scores were recorded. Success was determined as the proportion of patients achieving at least a 75% improvement in the PASI score from baseline (PASI 75). At 60 months after commencement of therapy, 31% of patients remained on infliximab. Those who did retained PASI 75 with a DLQI of 0 or 1. Of those who ceased infliximab, nine did so due to loss of efficacy, three for personal reasons, two for serious adverse events and one was lost to follow up. Adverse events included non‐melanoma skin cancers, infections and abnormal liver enzymes. Infliximab in the Australian context has proven to be a highly effective treatment of chronic plaque psoriasis, and patients who remained on the drug derived a high level of satisfaction, assessed both subjectively (DLQI) and objectively (PASI 75). The variable response indicates that psoriasis is a heterogeneous disease and investigation into potential patient selection for treatment in the future is warranted.     

Systematic review on the maintenance of response during systemic antipsoriatic therapy

As a chronic disease psoriasis often requires long‐term treatment. Successful continuation of therapy during a maintenance phase is therefore important. A systematic review was performed on the efficacy of psoriasis drugs during maintenance treatment in patients who had achieved sufficient treatment success during the induction period. Maintenance therapy is defined as treatment during the period after successful induction therapy. Inclusion criteria were prospective studies with systemic therapies recommended by the 2009 European psoriasis guidelines (plus ustekinumab), and a study population that had achieved a defined treatment response criterion after induction therapy within a period of ≥ 6 months. Maintenance studies on conventional treatments were identified for ciclosporin (CSA) only (no studies investigating acitretin, methotrexate or ustekinumab were found). Compared with placebo, CSA was shown to be effective in maintenance therapy, yet CSA 1·5 mg kg^?1 seems to be insufficient to maintain disease control. Based on the evidence, it is uncertain whether there is any difference between daily or intermittent treatment. For biologics, maintenance data were available for adalimumab, etanercept and infliximab. No differences in 75% improvement in Psoriasis Area and Severity Index (PASI 75) response were identified between adalimumab 40 mg once and twice a month. Continuous infliximab treatment was shown to be superior to as‐needed treatment. For etanercept, only observational postrandomized controlled trial data were available, indicating a maintained PASI 75 response in approximately three‐quarters of patients during long‐term treatment. Only limited evidence is available for a conclusion on how patients with an adequate response should be optimally treated during the maintenance period. A clear ranking of the available treatments is not yet possible.     

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.     

Ustekinumab does not increase body mass index in patients with chronic plaque psoriasis: a prospective cohort study

Background Chronic plaque psoriasis is frequently associated with metabolic disorders including obesity. Antitumour necrosis factor α treatments can induce body‐weight increase in patients with psoriasis. Information on the effect of ustekinumab on body weight is not available. Objectives To investigate whether therapy with ustekinumab is associated with changes in body mass index (BMI) in patients with chronic plaque psoriasis. Methods A prospective, multicentre study comparing the changes in BMI in two closed cohorts of patients with psoriasis during 7‐month treatment with ustekinumab (n = 79) or infliximab (n = 83). Results Patients treated for 7 months with infliximab showed a significant (P < 0·001) increase in mean BMI (2·1 ± 4·5%) and body weight (2·5 ± 3·3 kg) compared with patients treated with ustekinumab (0·1 ± 3·3%; 0·6 ± 1·1 kg). Some 45% of patients treated with infliximab had a BMI increase > 2%, compared with only 11% of those receiving ustekinumab (P = 0·01). In the multivariate analysis, all other clinical parameters predicted the BMI increase, except for the use of infliximab. At month 7, 96% of patients treated with infliximab and 82% of patients treated with ustekinumab achieved at least a 50% improvement from their baseline psoriasis area and severity index (PASI 50), and 69% of the infliximab group compared with 58% of the ustekinumab group achieved at least PASI 75. There was no difference in the proportion of PASI 50 and PASI 75 responders between the two groups. Conclusions In contrast to infliximab, ustekinumab does not increase BMI in patients with chronic plaque psoriasis. This difference could be taken into account in the selection of biologics when treating patients with psoriasis.     

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

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

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.     

Long-term study of infliximab in Japanese patients with plaque psoriasis, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma

The efficacy and safety of infliximab in patients with plaque psoriasis, psoriatic arthritis, pustular psoriasis (excluding localized type) and psoriatic erythroderma were assessed in clinical practice. Without washout of the existing treatment of psoriasis, treatment was switched to infliximab, which was given at a dose of 5 mg/kg at weeks 0, 2 and 6 and then every 8 weeks up to week 46. The primary end-points were 75% improvement in Psoriasis Area and Severity Index score (PASI 75 response rate) for plaque psoriasis, 20% improvement in American College of Rheumatology criteria (ACR 20 response rate) for psoriatic arthritis, and global improvement in pustular psoriasis and psoriatic erythroderma. The PASI 75 response rate in plaque psoriasis was 72.2% at week 10 and 53.6% at week 50. The ACR 20 response rate in psoriatic arthritis was 66.7% at week 14 and 80.0% at week 46. The response defined as global improvement in pustular psoriasis was between 66.7% and 100.0% during the 2–50-week period. The response defined as global improvement in psoriatic erythroderma was between 75.0% and 100.0% during the week-2–50 period. There were 14 discontinued patients. The most frequently reported reason for discontinuation was the development of adverse events. However, there were no serious respiratory diseases, infections or infusion reactions. In patients with plaque psoriasis, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma, infliximab was well tolerated, regardless of prior treatment, and also showed superior efficacy over a period of approximately 1 year.     

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.     

Etanercept

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

Relationship between methotrexate dosing and clinical response in patients with moderate to severe psoriasis: subanalysis of the CHAMPION study

Background CHAMPION was a phase III trial that compared adalimumab with methotrexate and placebo for chronic plaque psoriasis. Objectives To determine the relationship between methotrexate dosing and improvement in psoriasis for patients in CHAMPION. Methods Methotrexate‐treated patients in CHAMPION received step‐up dosing to 15 mg per week during the first 8 weeks. At week 8, PASI 50 responders (early responders, ER) were to continue with 15 mg weekly for the next 8 weeks; PASI 50 nonresponders were to receive 20 mg weekly for the next 4 weeks, followed by 20 mg weekly if they achieved ≥ PASI 50 at week 12 (late responders, LR), or 25 mg weekly if not (late nonresponders, LN). Outcomes were assessed post hoc for patients in these groups who completed CHAMPION. Results One hundred and three methotrexate‐treated patients were analysed: 40 ER, 22 LR and 41 LN. Week 16 mean percentage improvement from baseline in Psoriasis Area and Severity Index was greatest in the ER group, nearly as good in LR, and poor in LN; PASI 75/90/100 response rates were 70%/32%/18%, 41%/9%/5% and 5%/0%/0%, respectively. Among patients with a PASI 75 response at week 16, 72% were in the ER group (comprising 27% of patients overall) and 23% were in the LR group. Conclusions Nearly all week 16 PASI 75 responders in CHAMPION achieved a PASI 50 response at week 8 or 12, with maximum methotrexate dosages of 15 or 20 mg per week, respectively. Week 12 may be an appropriate time to discontinue methotrexate treatment in patients who are not achieving good responses.     

The combination of etanercept and methotrexate increases the effectiveness of treatment in active psoriasis despite inadequate effect of methotrexate therapy

Many patients with moderate-to-severe plaque psoriasis do not respond adequately to methotrexate monotherapy. This pilot study, with a small patient population, was performed to evaluate the effectiveness and safety of etanercept and methotrexate combination in patients with plaque psoriasis and inadequate response to methotrexate. Outpatients with plaque psoriasis (Psoriasis Area and Severity Index >/= 8 and/or body surface area > 10%), despite methotrexate treatment (>/= 3 months; >/= 7.5 mg/week) were randomized to either etanercept with metho nottrexate tapered and discontinued (n = 28) or etanercept with continuous methotrexate (n = 31). Significantly more patients had a Physicians' Global Assessment of "clear"/"almost clear" in the combination group compared with etanercept/methotrexate taper (66.7 vs. 37.0%, respectively; p = 0.025). Adverse events were similar for both groups, with no cases of tuberculosis, malignancies or opportunistic infections reported. Addition of etanercept to methotrexate achieved significant improvement in psoriasis after 24 weeks.     

Methotrexate and ciclosporin combination for the treatment of severe psoriasis

BACKGROUND: Psoriasis is a chronic skin disease that often requires long-term therapy to control the symptoms. Combination therapies for severe psoriasis have advantages for disease control and are thought to reduce long-term side-effects. OBJECTIVE: To assess the efficacy and side-effects of methotrexate plus ciclosporin used in combination for the treatment of severe psoriasis. METHODS: In this prospective study, 20 patients were treated with the combination of methotrexate and ciclosporin. Methotrexate was given intramuscularly as a single weekly dose of 10 mg and ciclosporin at a dose of 3.5 mg/kg/day in two equally divided doses. Clinical response was assessed according to clinical outcome and the Psoriasis Area and Severity Index which were evaluated at the beginning of therapy (PASI1), after cessation of one agent (PASI2), and at the end of therapy (PASI3). RESULTS: All the patients had previously received one or more systemic treatment. There were 10 women and 10 men (mean age 44 years). The median (minimum to maximum) duration of methotrexate and ciclosporin treatments were 12.5 (4-55) and 14.0 (4-80) weeks, respectively. Median duration of combination therapy was 9.5 weeks (range 4-50). The median of previously used and end-of-study cumulative doses of methotrexate were 181.8 mg (range 0-785) and 330.8 mg (range 50-845), respectively. The median PASI scores were decreased by 77.4% (range 51.2-90.2) and 75.9% (range 10.1-100) at PASI2 and PASI3, respectively. CONCLUSION: Patients with severe psoriasis had clinically significant improvement after the initiation of combination therapy. Healing rate was decreased upon cessation of one of the medications. Short-term side-effects were minor, transient and manageable. Long-term follow-up of patients treated with this combination is needed.     

Efficacy and safety results from the randomized controlled comparative study of adalimumab vs. methotrexate vs. placebo in patients with psoriasis (CHAMPION)

BACKGROUND: Biologic therapies such as adalimumab, a tumour necrosis factor antagonist, are safe and effective in the treatment of moderate to severe chronic plaque psoriasis. OBJECTIVES: To compare a biologic agent with methotrexate, a traditional systemic agent, to define clearly the role of biologics in psoriasis. METHODS: Patients with moderate to severe plaque psoriasis were randomized to adalimumab (80 mg subcutaneously at week 0, then 40 mg every other week, n=108), methotrexate (7.5 mg orally, increased as needed and as tolerated to 25 mg weekly; n=110) or placebo (n=53) for 16 weeks. The primary efficacy endpoint was the proportion of patients achieving at least a 75% improvement in the Psoriasis Area and Severity Index (PASI 75) after 16 weeks. Safety was assessed at all visits through week 16. RESULTS: After 16 weeks, 79.6% of adalimumab-treated patients achieved PASI 75, compared with 35.5% for methotrexate (P<0.001 vs. adalimumab) and 18.9% for placebo (P<0.001 vs. adalimumab). Statistically significantly more adalimumab-treated patients (16.7%) than methotrexate-treated patients (7.3%) or placebo-treated patients (1.9%) achieved complete clearance of disease. The response to adalimumab was rapid, with a 57% improvement in mean PASI observed at week 4. Adverse events were similar across treatment groups. Adverse events leading to study discontinuation were greatest in the methotrexate group, primarily because of hepatic-related adverse events. CONCLUSIONS: After 16 weeks, adalimumab demonstrated significantly superior efficacy and more rapid improvements in psoriasis compared with either methotrexate or placebo.     

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.     

Patients with moderate-to-severe psoriasis recapture clinical response during re-treatment with etanercept

Background  Patients with psoriasis experience remission and gradual reappearance of erythematous and scaly plaques and require individualized treatment over time. A goal of psoriasis treatment is to provide optimal efficacy with a flexible therapeutic regimen that may include treatment pauses.
Objectives  To determine whether patients receiving initial treatment with etanercept who then pause therapy would subsequently recapture response during re-treatment.
Patients and methods  A post-hoc analysis of 226 patients with moderate-to-severe psoriasis from a large multicentre trial was performed. Patients had received etanercept 50 mg twice weekly subcutaneously until a target clinical response had been achieved, then had paused treatment and eventually relapsed. They were then re-treated with etanercept 25 mg twice weekly. The number of patients recapturing a Physician Global Assessment (PGA) of psoriasis rating of ≤ 2 (clear, almost clear or mild) on first re-treatment was assessed. Patient satisfaction during the initial treatment and first re-treatment period was also determined.
Results  A total of 187 (83%) patients recaptured the target clinical response of a PGA of ≤ 2 after re-treatment. The majority of patients [219 of 226 (97%)] reported satisfaction with etanercept re-treatment. No new safety concerns emerged during re-treatment.
Conclusions  In this post-hoc analysis, patients with psoriasis who were re-treated with etanercept 25 mg twice weekly effectively recaptured clinical responses that patients found satisfactory. A flexible treatment option is available to dermatologists and patients for individualized care.