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.     

Long-term efficacy of ustekinumab in patients with moderate-to-severe psoriasis: results from the PHOENIX 1 trial through up to 3 years

Background An unmet need remains for safe and effective long‐term treatments of psoriasis. Objectives To evaluate ustekinumab efficacy and safety for up to 3 years in the PHOENIX 1 trial. Methods Patients (n = 766) with moderate‐to‐severe psoriasis were randomized to ustekinumab 45 mg or 90 mg at weeks 0 and 4, and then every 12 weeks, or placebo at weeks 0 and 4, with crossover to ustekinumab at week 12. Ustekinumab responders [≥ 75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) at weeks 28 and 40] were re‐randomized at week 40 to continue or withdraw from treatment until psoriasis recurrence. Partial responders (week 28: PASI 50–74; week 40: < PASI 75) switched to dosing every 8 weeks. Clinical efficacy was assessed by PASI, the Physician’s Global Assessment (PGA), and the Dermatology Life Quality Index (DLQI) measures. Results Overall, 79·8% of the ustekinumab‐treated patients remained in the study for 3 years. PASI 75 response rates (45 mg: 61·2%; 90 mg: 72·4%) at week 76 were maintained through year 3 (45 mg: 62·7%; 90 mg: 72·2%); PGA response was similarly durable. At year 3, 80·9% (45 mg) and 82·7% (90 mg) of week 40 responders continuing treatment every 12 weeks achieved a PASI 75 response, while 42·6% (45 mg) and 58·0% (90 mg) achieved a PASI 90 response. Among partial responders adjusted to dosing every 8 weeks, 50·9% (45 mg) and 52·0% (90 mg) had a PASI 75 response at year 3. DLQI responses paralleled the PASI responses. Through year 3, no dose response was observed in rates of adverse events (AEs), overall infections, serious AEs, or AEs leading to discontinuation; nor was there evidence of cumulative organ toxicity. Conclusions Continuous, stable, maintenance dosing with ustekinumab was generally well tolerated and sustained durable efficacy for up to 3 years of treatment.     

Long‐term efficacy of ustekinumab in patients with moderate‐to‐severe psoriasis treated for up to 5 years in the PHOENIX 1 study

Background Ongoing evaluation of biological agents in patients with moderate‐to‐severe psoriasis is needed to support their long‐term use. Objective To evaluate long‐term efficacy and safety of ustekinumab through 5 years in the PHOENIX 1 study. Methods Patients were randomized to placebo or ustekinumab (45 mg or 90 mg) at Weeks 0, 4 and every‐12‐weeks thereafter; placebo patients crossed‐over to ustekinumab at Week 12. Clinical response through Week 244 was evaluated using the Psoriasis Area and Severity Index (PASI) in the Overall Population (i.e. patients receiving ≥1 dose of ustekinumab), Initial Responders (i.e. PASI 75 responders [Weeks 28/40] re‐randomized at Week 40 to continue every‐12‐week maintenance) and Partial Responders (i.e. <PASI 75 responders adjusted to every‐8‐week maintenance at Weeks 28 or 40). Safety endpoints were evaluated through Week 264 for the Overall Population. Results  Overall, 68.7% (517/753) of ustekinumab‐treated patients completed treatment through Week 244. Initial clinical responses were generally maintained through Week 244 (PASI 75: 63.4% and 72.0%; PASI 90: 39.7% and 49.0%; PASI 100: 21.6% and 26.4%) for patients receiving 45 mg and 90 mg, respectively. Similarly, PASI 75 responses were generally maintained among Initial Responders [79.1% (45 mg) and 80.8% (90 mg)] and Partial Responders [57.6% (45 mg) and 55.1% (90 mg)]. With 3104 patient‐years of follow‐up, rates of overall adverse events (AEs), serious AEs, serious infections, malignancies and major adverse cardiovascular events were generally consistent over time and comparable between doses. Conclusions Through 5 years of continuous treatment, ustekinumab demonstrated stable clinical response and a safety profile consistent with previous reports.     

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.     

Transitioning patients from efalizumab to alternative psoriasis therapies: findings from an open-label, multicenter, Phase IIIb study

BACKGROUND: Rebound in psoriasis is, by definition, a rapid worsening of disease following the discontinuation of therapy for psoriasis; it occurs following the abrupt discontinuation of many therapies. To prevent rebound on discontinuation of efalizumab, this study evaluated the effectiveness of transitioning patients to an alternative psoriasis therapy. METHODS: Patients (n = 130) received subcutaneous efalizumab 1 mg/kg/week for 12 weeks. Efalizumab was discontinued at 12 weeks; patients were evaluated for improvement from baseline in the Psoriasis Area and Severity Index (PASI) and a 12-week transition period was begun. Patients who achieved PASI improvement of 75% or more (PASI-75) at week 12 of efalizumab treatment were observed during the transition period and treated only if psoriasis recurred. Patients who did not attain PASI-75 at week 12 of efalizumab treatment were immediately transitioned to an alternative psoriasis therapy at the physician's discretion. All patients were evaluated for signs of rebound following efalizumab discontinuation. RESULTS: Rebound was not observed in any PASI-75 responder (n = 46). Rebound was observed in two of 32 patients who achieved between PASI-50 and PASI-75, and was more common in nonresponders (14/49). Rebound was observed in none of the eight patients treated with cyclosporine and in two of the 12 patients treated with methotrexate during the transition period. CONCLUSIONS: These results suggest that efalizumab-responsive patients are less likely to experience rebound than nonresponders and may not require treatment until disease recurrence following efalizumab discontinuation. Efalizumab nonresponders are at higher risk of developing rebound and thus should be considered for transition to an appropriate psoriasis therapy immediately following efalizumab discontinuation.     

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.     

Efficacy and safety of etanercept in the treatment of recalcitrant psoriasis: An open-label,retrospective, observational study in Taiwan

BackgroundPsoriasis is a chronic inflammatory disease affecting the quality of life of patients. Traditional treatments are limited by adverse side effects. Etanercept is a biological agent used as an alternative treatment for psoriasis.MethodsThis open-label, observational study conducted in Taiwan involved 22 patients with recalcitrant psoriasis who received a 24-week treatment with etanercept—50 mg twice weekly (BIW) during the first 12 weeks and 25 mg BIW in the next 12 weeks. Psoriasis Area and Severity Index (PASI) score at Weeks 0, 12, and 24 were recorded. Levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antinuclear antibody (ANA), and tumor necrosis factor-alpha (TNF-α) at baseline, Week 12, and Week 24 were obtained. Adverse events and blood tests were recorded as safety assessment.ResultsAt Week 12, 54.5% and 13.6% patients achieved ≥50% improvement from baseline in PASI score (PASI 50 and PASI 75, respectively); at Week 24, 66.7% and 23.8% patients achieved PASI 50 and PASI 75, respectively. The mean improvement in PASI was 49.8% at Week 12 and 59.8% at Week 24, while 100% and 62.5% patients had reduced ESR and CRP levels, respectively. There were no deaths or serious adverse events. Four patients developed positive ANA, one of whom had poor psoriasis control. Most patients (93.8%) had higher serum TNF-α levels compared to baseline.ConclusionsEtanercept is effective and safe in treating recalcitrant psoriasis, reduces ESR and CRP levels, and occasionally induces positive ANA titer associated with poor psoriasis control. Serum TNF-α level may increase after treatment, but this does not seem to affect PASI improvement.     

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.     

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.     

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.     

Open-label, single-center, safety dose escalation trial of alefacept for the treatment of moderate to severe chronic plaque psoriasis

BACKGROUND: Alefacept (Amevive) is a fully human LFA-3/IgG1 fusion protein with a dual mechanism of action inhibiting T-cell activation and selectively reducing memory T cells. Alefacept is currently approved as a 12-week course of weekly 15 mg intramuscular (IM) injections for the treatment of adults with moderate to severe chronic plaque psoriasis. In clinical trials using the currently approved dosing regimen, 33% and 57% of patients achieved a 75% or greater or 50% or greater reduction in Psoriasis Area and Severity Index score (PASI 75 and PASI 50), respectively, after one course of alefacept. OBJECTIVE: To evaluate the tolerability and efficacy of alefacept 15 mg IM weekly for 6 weeks followed by alefacept 30 mg IM weekly for 6 weeks. DESIGN: Open-label, single-center, dose escalation study of alefacept. PATIENTS: Adult patients with chronic plaque psoriasis involving a minimum body surface area of 10% and with a minimum PASI of 12. INTERVENTION: Patients were treated with alefacept 15 mg IM for 6 weeks followed by alefacept 30 mg IM for an additional 6 weeks; doses were held for CD4 counts < 200 cells/mm(3) or evidence of a clinically significant infection. MAIN OUTCOME MEASURE: Efficacy was evaluated by PASI and Physician Global Assessment (PGA) at baseline, week 7, and 2, 6, 12, and 24 weeks post-treatment. RESULTS: Sixteen patients were enrolled; at 6 weeks post-treatment, the PASI mean reduction was 39%, with continued improvement to 46% at 12 weeks post-treatment. The PASI 90, PASI 75, and PASI 50 responses at 12 weeks post-treatment were 6% (1 of 16), 13% (2 of 16), and 38% (6 of 16), respectively; 12% (2 of 16) of patients achieved a PGA of clear to almost clear at 12 weeks post-treatment. The overall PASI 75 and PASI 50 responses were 19% (3 of 16) and 38% (6 of 16), respectively. CONCLUSION: The treatment regimen of alefacept 15 mg IM for 6 weeks followed by alefacept 30 mg IM for 6 weeks was well tolerated by our patients. There was no increased incidence of infections when patients were treated with alefacept 30 mg compared with the 15 mg dose. The increased dose of alefacept 30 mg for the last 6 weeks of a 12-week course did not appear to yield a higher efficacy rate compared with historical controls.     

Subcutaneous methotrexate in patients with moderate‐to‐severe psoriasis: a critical appraisal

This article is a review of a study, published in the Lancet, by R.Warren and colleagues, based in the U.K. and western Europe. The authors compared 17.5mg weekly methotrexate, given by subcutaneous injection, with placebo in 120 patients with moderate to severe psoriasis who had not previously received the drug. The first sixteen weeks of the study were a randomised controlled trial, meaning patients were randomly selected to either receive the drug or a placebo; patients continued an open study on methotrexate for up to a year. The dose was increased to 22.5 mg weekly if they did not improve on the lower dose to achieve PASI 50 at week 24. PASI is used to record the redness, thickness and scaling of a patient's psoriasis and to measure how well a treatment works, as a reduction in the PASI score means a reduction in these symptoms; for example PASI 75 means the patient has a 75% or more reduction in their PASI score from the start. The authors took blood tests and skin biopsies from patients on methotrexate and found changes on microscopic examination, including a decrease in CD3 positive lymphocytes and cytokine markers, and this implies that the drug works by its effect on the immune system. Blood tests showed no significant abnormality. At week 16, 41% of patients on methotrexate achieved PASI 75 improvement, compared to 10% of patients on placebo. The reviewers observed that, although methotrexate is widely used as a systemic treatment for psoriasis, there have been no previous randomised placebo controlled trials. This trial is therefore welcome, although only the first phase is placebo controlled. Traditionally, patients are given a small test dose (e.g. 5 or 7.5mg), and the dose is increased gradually over successive weeks. The investigators encountered no adverse events from starting on a higher dose. The reviewers noted that methotrexate by injection was not compared with the oral form of the drug (taken by mouth), which might be equally effective and is substantially cheaper. The unusually high response to placebo may be due in part to alcohol avoidance, which is advised for patients on methotrexate. The changes on skin biopsy are of interest, but it was not possible to correlate them with clinical response to the drug.     

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.     

Efficacy and safety of cyclosporine versus methotrexate in severe psoriasis: a study from north India

Treatment of patients with severe psoriasis is difficult. Among the number of systemic drugs that are available, methotrexate has long been used, but cyclosporine has been recently recommended for the management of severe psoriasis. The purpose of this study was to compare the efficacy and safety of daily cyclosporine with weekly methotrexate in the management of severe psoriasis. Thirty consecutive patients with severe psoriasis were randomly assigned to treatment with cyclosporine or methotrexate. The initial dose of cyclosporine was 3 mg/kg/day, which was increased to a maximum of 4 mg/kg after two weeks of therapy when the response was not adequate. Methotrexate was administered weekly at a dose of 0.5 mg/kg. Clinical response was assessed by calculating PASI score in all patients at biweekly intervals. Patients were followed up fortnightly up to a maximum of 12 weeks. The doses of both drugs were gradually tapered once >75% reduction in disease severity was attained. Marked improvement (>75%) reduction in PASI was noted in all patients except for one in the cyclosporine group. The median time for marked improvement was 5.3 weeks with methotrexate and 6.8 weeks with cyclosporine. Patients on methotrexate were found to have more rapid and complete clearance than those on cyclosporine. Both drugs were well tolerated. Side effects in both the treatment groups were minor, transient, and manageable. At doses with comparable safety profiles, methotrexate resulted in more rapid and cost effective clearance of patients with severe psoriasis. Cyclosporine can provide an effective and safe alternative.     

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.     

Secukinumab efficacy and safety in Japanese patients with moderate‐to‐severe plaque psoriasis: Subanalysis from ERASURE,a randomized,placebo‐controlled,phase 3 study

Secukinumab, a fully human anti‐IL‐17A monoclonal antibody, neutralizes IL‐17A, a key cytokine in the pathogenesis of psoriasis. Efficacy and safety of secukinumab was evaluated in Japanese patients with moderate‐to‐severe plaque psoriasis as part of a large Phase 3 global study (ERASURE). In this 52‐week, double‐blind study (ClinicalTrials.gov Identifier: NCT01365455, JapicCTI‐111529), 87 patients from Japan (11.8% of 738 patients randomized in the overall study population) were equally randomized to receive secukinumab 300 mg or 150 mg, or placebo once weekly at baseline and at Weeks 1, 2, 3 and 4, then every 4 weeks. Co‐primary endpoints (Week 12) were ≥75% improvement in psoriasis area‐and‐severity index (PASI 75) from baseline and a score of 0 (clear) or 1 (almost clear) on a 5‐point Investigator's Global Assessment scale (IGA mod 2011 0/1) versus placebo. PASI 75 and IGA mod 2011 0/1 responses at Week 12 were superior with secukinumab 300 mg (82.8% and 55.2%, respectively) or 150 mg (86.2% and 55.2%, respectively) versus placebo (6.9% and 3.4%, respectively; P < 0.0001 for all). Greater than 90% improvement in PASI (PASI 90) was also superior with secukinumab 300 mg (62.1%) or 150 mg (55.2%) versus placebo (0.0%) at Week 12 (P < 0.0001 for both). Clinical responses were sustained up to Week 52 in the majority of patients. During a 12‐week induction period, adverse event incidences were 48.3% with secukinumab 300 mg, 55.2% with 150 mg, and 41.4% with placebo. Secukinumab showed robust and sustainable efficacy in symptom reduction for moderate‐to‐severe plaque psoriasis in the Japanese patients.     

Treatment of psoriasis with recombinant human LFA3-antibody fusion protein: a multi-center, randomized, double-blind trial in a Chinese population

To evaluate clinical efficacy and safety of injectable recombinant human LFA3-antibody fusion protein (rhLFA3-IgFP), a multi-center, randomized, double-blind, double-dummy, parallel-controlled clinical trial was performed in 212 cases of moderate to severe psoriasis. Intramuscular injection of rhLFA3-IgFP (15 mg/week) and oral administration of blank dummy methotrexate at the dose of 7.5 mg/week was performed in the patients in the experimental group, and control patients were orally administered with methotrexate at the dose of 7.5 mg/week and intramuscularly injected with the blank dummy rhLFA3-IgFP (15 mg/week). PASI was determined prior to and at 2, 4, 6, 8, 12, 16, 20 weeks after the treatment. The efficacy evaluation was carried out on 192 patients, and no significant differences were found in PASI50, PASI75 & PASI90 between the two groups after twelve weeks' treatment (p>0.05). After discontinuation, PASI scores continued to decrease drastically in the experiment group, whereas they increased in the control group. At 8 weeks after discontinuation, PASI scores were decreased by 62.32% (p<0.05) and 52.67% (p<0.05) in the experimental and control groups, respectively. No serious adverse reactions were observed. In conclusion, the results of our investigation demonstrated that rhLFA3-IgFP was an effective therapy for chronic plaque psoriasis with lasting action and low incidence of adverse reactions.     

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.     

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.     

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.