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.     

Successful treatment of moderate to severe plaque psoriasis with the PEGylated Fab' certolizumab pegol: results of a phase II randomized, placebo-controlled trial with a re-treatment extension

Background Certolizumab pegol (CZP) is a PEGylated antitumour necrosis factor agent. Objectives To evaluate the efficacy and safety of CZP in patients with plaque psoriasis. Methods In a randomized, placebo‐controlled, double‐blind study, 176 patients with moderate to severe psoriasis received placebo or CZP 400 mg at week 0 followed by placebo or CZP (200 or 400 mg) every other week until week 10. Co‐primary endpoints were ≥ 75% improvement from baseline in Psoriasis Area and Severity Index (PASI 75) and a Physician’s Global Assessment (PGA) of clear‐almost clear at week 12. A re‐treatment extension study was conducted in 71 CZP PASI 75 responders who relapsed during a 12‐ to 24‐week observation period without treatment. Results PASI 75 was achieved by 44/59 (75%), 48/58 (83%) and 4/59 (7%) patients in the CZP 200 mg, CZP 400 mg and placebo groups, respectively (P < 0·001 for both treatment arms vs. placebo). A PGA score of clear‐almost clear was achieved by 53%, 72% and 2%, respectively (P < 0·001 for both treatment arms vs. placebo). In the re‐treatment study median PASI scores were similar at week 12 in the first treatment and re‐treatment periods for both CZP groups. Serious adverse events occurred in 3%, 5% and 2% of CZP 200 mg, CZP 400 mg and placebo patients, respectively. Conclusions Treatment with CZP significantly improved psoriasis at week 12. Similar efficacy was observed at week 12 in patients receiving re‐treatment for loss of response after drug withdrawal.     

Treatment of plaque‐type psoriasis with oral CF101: data from an exploratory randomized phase 2 clinical trial

Aims CF101 demonstrated a marked anti‐inflammatory effect in Phase 2 studies conducted in patients with rheumatoid arthritis and dry eye syndrome. The aim of this study was to evaluate the safety and efficacy of CF101 for the treatment of patients with moderate to severe plaque‐type psoriasis. Materials and methods This was a phase 2, multicentre, randomized, double‐blind, dose‐ranging, placebo‐controlled study. Seventy five patients with moderate to severe plaque‐type psoriasis were enrolled, randomized and treated with CF101 (1, 2, or 4 mg) or placebo administered orally twice daily for 12 weeks. Safety and change from base line of Psoriasis Area and Severity Index (PASI) score and physician’s global assessment (PGA) score over 12 weeks. Results In the 2 mg CF101‐treated group, a progressive improvement in the mean change from baseline in the PASI score vs. placebo throughout the study period was observed, with a statistically significant difference on weeks 8 and 12 (P = 0.047; P = 0.031, respectively). In this group, 35.3% of the patients achieved PASI ≥50 response, and 23.5% of the patients achieved a PGA score of 0 or 1. CF101 was safe and well tolerated. Conclusions CF101 was well tolerated and demonstrated clear evidence of efficacy in patients with moderate to severe plaque psoriasis.     

Efficacy and safety of topical WBI‐1001 in patients with mild to moderate psoriasis: results from a randomized double‐blind placebo‐controlled,phase II trial

Background There is a need for the development of novel non‐steroidal topical drugs for the treatment of psoriasis. Objective To assess the efficacy and safety of topical 1.0% WBI‐1001 in patients with mild to moderate plaque psoriasis. Methods A total of 61 patients with 1–10% body surface area (BSA) covered with plaque psoriasis and a physician’s global assessment score (PGA) of 2–4 were randomized (2 : 1) to receive either 1% WBI‐1001 in a cream formulation or placebo, applied twice daily for 12 weeks. Efficacy was evaluated using PGA, BSA and Psoriasis Area and Severity Index (PASI). The primary endpoint was the change from baseline (Day 0) in PGA at week 12. Results The improvement in PGA at week 12 was 62.8% for patients randomized to WBI‐1001 when compared with 13.0% for patients randomized to placebo (P < 0.0001). At week 12, the proportion of patients who achieved a PGA of clear or almost clear and the mean improvement in BSA were 67.5% and 79.1%, respectively, for patients randomized to WBI‐1001, when compared with 4.8% (P < 0.0001) and an increase of 9.4% (P < 0.0001), respectively, for patients randomized to placebo. More application site adverse drug reactions were observed in patients randomized to WBI‐1001 than in those randomized to placebo. These adverse drug reactions were all mild or moderate in intensity. Conclusion Topical WBI‐1001 induces rapid and significant improvement in patients with plaque psoriasis.     

Methotrexate/narrowband UVB phototherapy combination vs. narrowband UVB phototherapy in the treatment of chronic plaque‐type psoriasis – a randomized single‐blinded placebo‐controlled study

Background Psoriasis is a chronic, recurring inflammatory disease affecting the skin, joints and nails that has a significant negative impact on the quality of life. Efficacy of combination of methotrexate/narrowband ultraviolet B (NBUVB) phototherapy in the treatment of psoriasis has been rarely assessed. Objectives To compare the efficacy of methotrexate/NBUVB phototherapy combination vs. NBUVB phototherapy in the treatment of chronic plaque psoriasis. Methods Forty patients with chronic plaque‐type psoriasis (body surface area involvement >10%) were randomized to receive either methotrexate/NBUVB phototherapy (group A) or placebo/NBUVB phototherapy (group B). End point of treatment was 75% reduction in Psoriasis Area and Severity Index (PASI) Score or upto 6 months, whichever was earlier. Patients were then followed up for a period of 12 weeks for assessment of relapse. Results Of 40 patients, 37 completed the treatment period and 29 both the treatment period and follow‐up. PASI 75 was achieved in 19/20 patients in group A and 14/20 patients in group B (P < 0.04). The mean number of weeks(P = 0.001), the mean cumulative dose of NBUVB (P = 0.001) and the mean number of phototherapy sessions (P = 0.0001) required to achieve PASI 75 were significantly less in group A compared with group B. There was no significant difference in the number of patients who relapsed during the follow‐up period (P = 0.68). Conclusion Combination of methotrexate and NBUVB phototherapy provides more rapid clinical improvement compared with NBUVB monotherapy in the treatment for chronic plaque‐type psoriasis.     

Efficacy and safety of ustekinumab in Japanese patients with moderate-to-severe plaque-type psoriasis: long-term results from a phase 2/3 clinical trial

This phase 2/3, double-blind, placebo-controlled study was designed to assess the safety and efficacy of ustekinumab in Japanese patients with moderate-to-severe plaque-type psoriasis. Overall, 158 patients were randomized to receive ustekinumab 45 or 90 mg at weeks 0, 4, and every 12 weeks, or placebo with cross-over to ustekinumab at week 12. The primary end-point was the proportion of patients achieving at least 75% improvement in Psoriasis Area and Severity Index (PASI 75) at week 12. Physician's Global Assessment (PGA), Dermatology Life Quality Index (DLQI), Nail Psoriasis Severity Index and joint pain Visual Analog Scale (VAS) were also measured. At week 12, 59.4% and 67.7% of ustekinumab 45 and 90 mg patients achieved PASI 75, respectively, compared with 6.5% in the placebo group (P < 0.0001 each). PASI 75 responses were maintained through week 64 in 65.0% and 78.6% of the ustekinumab-treated patients, respectively. Placebo cross-over patients had similar responses to ustekinumab-treated patients. Significant improvements in PGA, DLQI and VAS scores were observed at week 12 and generally maintained over time. Adverse events during the placebo-controlled period were similar among groups (45 mg, 65.6%; 90 mg, 59.7%; placebo, 65.6%). Serious adverse events were observed in 0%, 4.8% and 6.3% of patients, respectively. Through week 72, similar rates and types of adverse events and serious adverse events were reported in patients receiving 45 and 90 mg. Rates of injection site reactions and antibodies to ustekinumab were low. Ustekinumab was efficacious and generally well-tolerated in Japanese patients with moderate-to-severe plaque-type psoriasis through 72 weeks. These results are consistent with those reported in the global, phase 3 studies.     

Evaluation of the efficacy of methotrexate and cyclosporine therapies on psoriatic nails: a one‐blind,randomized study

Background Treatment of psoriatic nail is difficult. Objective The aim of this study was to evaluate and compare the efficacy and safety of methotrexate and cyclosporine in psoriatic nail. Methods Thirty‐seven psoriatic patients with nail involvement were randomized to treatment with methotrexate (initial dose, 15 mg per week) or cyclosporine (initial dose, 5 mg per kg of bodyweight per day) for 24 weeks. The primary outcome was the Nail Psoriasis Severity Index (NAPSI). The Psoriasis Area and Severity Index (PASI), doctor and patient global score were also measured. The scores were determined by a blinded observer. Results Seventeen patients completed the study in each group. The mean percentages of reduction of the NAPSI score after methotrexate and cyclosporine treatments were 43.3% and 37.2%, respectively. No significant differences between the treatment groups was found for in the NAPSI, PASI, physician’s and patient’s global score at the end of the study period. The methotrexate group showed a significant improvement in nail matrix scores and the cyclosporine group in nail bed score. Conclusion Moderate effectiveness on psoriatic nail was found in the two treatment agents and there were no significant differences in efficacy between the groups. A significant improvement was detected in methotrexate group for the nail matrix findings, and in cyclosporine group for the nail bed findings.     

Combination TL01 ultraviolet B phototherapy and topical calcipotriol for psoriasis: a prospective randomized placebo-controlled clinical trial

BACKGROUND: Previous studies have demonstrated the ultraviolet (UV)-sparing effect of combining topical calcipotriol with broadband UVB in the treatment of psoriasis. OBJECTIVES: To determine if the combination of narrowband TL01 UVB phototherapy and topical calcipotriol produces the same UVB-sparing effect. METHODS: This was a randomized, placebo-controlled, blinded clinical trial. Fifty psoriasis patients were recruited, 25 of whom were randomized into the active group who received TL01 phototherapy together with twice-daily application of calcipotriol cream 50 microg g(-1). The control group received TL01 phototherapy and twice-daily application of a topical emollient as placebo. TL01 phototherapy was given three times per week starting at 70% minimal erythema dose with 20% increments as tolerated for up to approximately 20 sessions. Patients were assessed using the Psoriasis Area and Severity Index (PASI) and Psoriasis Disability Index (PDI). They were evaluated at treatment sessions 8, 14 and 20, and followed up at 5 and 10 weeks post-treatment. Statistical analysis was performed using a two-tailed t-test. RESULTS: There were no significant differences in demographic characteristics and baseline PASI and PDI scores between the two groups. The mean PASI score declined significantly (P < 0.01) for both groups after treatment. The difference in mean PASI score reduction from baseline between the two groups was only significant during the first eight sessions, with a net reduction of 3.6 (95% confidence interval 1.0-6.2, P = 0.008) in the active group relative to the control group. The mean PDI score declined significantly (P < 0.05) for both groups, but there was no statistical difference in mean PDI score reduction between the two groups (P = 0.8) at the end of treatment. The mean cumulative UVB dose for the active group was significantly lower (P < 0.02) at 16 204 mJ cm-2 compared with 21 082 mJ cm-2 for the control group. CONCLUSIONS: We conclude that combining TL01 phototherapy with topical calcipotriol cream has a UVB-sparing effect.     

Folic acid supplementation during treatment of psoriasis with methotrexate: a randomized, double-blind, placebo-controlled trial

BACKGROUND: The value of folate supplementation in methotrexate (MTX)-treated patients remains controversial. OBJECTIVES: To determine the effect of folic acid (FA) on the efficacy of MTX and the frequency of side-effects associated with MTX therapy. METHODS: A 12-week double-blind clinical trial was conducted in patients with psoriasis stable on their long-term MTX doses but not receiving FA. They were randomized into two arms of either FA 5 mg or placebo daily. MTX doses were not changed throughout the study. Patients were monitored every 3 weeks by the same observer. Assessments included Psoriasis Area and Severity Index (PASI), a visual analogue scale (VAS) of patients' perception of their psoriasis severity and the Dermatology Life Quality Index (DLQI). Adverse events were systematically recorded. Haematological and biochemical monitoring was performed. RESULTS: Twenty-two patients with psoriasis were recruited. Age, sex and weekly MTX doses were similar in both groups. All 22 patients completed the study. The mean PASI in the FA group increased from 6.4 at baseline to 10.8 at 12 weeks. In the placebo group the mean PASI fell from 9.8 at baseline to 9.2 at 12 weeks. The mean change from baseline in the FA group was 4.4 vs. -0.6 in the placebo group (P < 0.05). Similar trends were observed in the changes in VAS and in the DLQI and differences between the groups were significant for both these parameters (P < 0.05). Few adverse effects were reported. CONCLUSIONS: This study suggests that supplementation with FA during long-term MTX treatment reduces the efficacy of MTX in the control of psoriasis. Due to the relatively small sample size and short duration of this study, no conclusions can be drawn regarding the possibility that FA may reduce the side-effects of MTX.     

Comparison of clobetasol propionate cream plus coal tar vs. topical psoralen and solar ultraviolet A therapy in palmoplantar psoriasis

Aim. Palmoplantar psoriasis (PPP) produces significant morbidity and requires prompt treatment. Topical agents form the mainstay of therapy. We compared the efficacy and side‐effect profile of a steroid/coal‐tar combination with topical psoralen and solar ultraviolet A (PUVAsol) in PPP. Methods. In total, 52 patients with PPP were randomized to receive either a combination of clobetasol propionate cream and coal tar daily (group 1) or topical PUVAsol on alternate days (group 2) for 16 weeks. Response was assessed as change in Psoriasis Activity and Severity Index (PASI) and Patient Global Assessment (PGA). Results. Of the 52 patients, 43 completed the treatment phase. There was a reduction in PASI for the palms and soles in both treatment groups throughout the treatment period until week 16. There was a greater reduction in PASI in palmar psoriasis with topical PUVAsol, and a greater reduction in psoriasis of the soles with the steroid/coal‐tar combination. In both groups, patients perceived ‘good improvement’. Improvement or cure in palmar lesions was observed in 90% of cases in the topical steroid/coal‐tar group and in 75% of cases in the topical PUVAsol group; for the soles, these figures were 76% and 79%, respectively. No adverse effects were experienced with the steroid/coal‐tar combination, whereas for the topical PUVAsol, phototoxicity occurred in 22% of cases. Conclusion. Both treatments had comparable efficacy. In both groups, patients experienced ‘good improvement’ after 16 weeks of therapy.     

Clinical benefits in patients with psoriasis after efalizumab therapy: clinical trials versus practice

Evaluations of efficacy of the new biologic therapies for psoriasis have used both physician-assessed endpoints and patient-reported outcome measures. The Psoriasis Area and Severity Index (PASI) is commonly used in clinical trials but is too labor intensive for clinical practice, which uses more subjective measures (physician global assessment [PGA] of change and Overall Lesion Severity [OLS] scale). Because psoriasis affects quality of life (QOL), patient-reported assessments of their satisfaction with treatment also are important. The purpose of this study was to evaluate some of the measurement tools used in clinical trials to make them more applicable to the practicing dermatologist. We used results of a placebo-controlled clinical study of efalizumab for the treatment of patients with moderate to severe plaque psoriasis. After treatment, ratings of improvement in psoriasis as measured by the PASI and PGA were closely aligned. It was noted the latter tool could provide a more practical and user-friendly evaluation in clinical practice. After 12 weekly subcutaneous injections of efalizumab, patients who achieved > or = 50% but < 75% improvement in PASI had treatment responses rated as primarily good or excellent using the PGA; additionally, the patients treated with efalizumab had statistically significant improvements (P<.001) in all patient-reported QOL assessments compared with placebo-treated patients, as did patients who achieved a > or = 75% improvement in PASI (PASI 75).     

Guselkumab,an anti‐interleukin‐23 monoclonal antibody,for the treatment of moderate to severe plaque‐type psoriasis in Japanese patients: Efficacy and safety results from a phase 3, randomized,double‐blind,placebo‐controlled study

Previous global studies of guselkumab have demonstrated clinical benefits in patients with psoriasis. The aim of this 52‐week, phase 3 study was to evaluate efficacy and safety of guselkumab in Japanese patients with moderate to severe plaque‐type psoriasis. Patients randomly received guselkumab 50 mg or 100 mg at weeks 0, 4 and every 8 weeks, or placebo with cross‐over to guselkumab 50 mg or 100 mg at week 16. Co‐primary end‐points were the proportion of patients achieving Investigator's Global Assessment (IGA) cleared/minimal (0/1) and 90% or more improvement in Psoriasis Area and Severity Index (PASI‐90) at week 16. Overall, 192 patients were randomized to placebo, guselkumab 50 mg or 100 mg. At week 16, patients in the placebo group were crossed over to guselkumab 50 mg or 100 mg. At week 16, a significantly (P < 0.001) higher proportion of patients receiving guselkumab 50 mg and 100 mg versus placebo achieved IGA 0/1 (92.3% and 88.9% vs 7.8%) and PASI‐90 (70.8% and 69.8% vs 0%). Patients in guselkumab 50 mg and 100 mg groups achieved significant improvement versus placebo in PASI‐75 (89.2% and 84.1% vs 6.3%, P < 0.001) at week 16; improvement was maintained through week 52. Incidences of treatment‐emergent adverse events were comparable among the groups through week 16; the most commonly reported was nasopharyngitis. No new safety concerns were observed until week 52. In conclusion, guselkumab treatment demonstrated superior efficacy over placebo and was well tolerated in Japanese patients with moderate to severe plaque‐type psoriasis.     

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.     

Methotrexate vs. ciclosporin in psoriasis: effectiveness, quality of life and safety. A randomized controlled trial

BACKGROUND: When this study was initiated, no previous studies comparing methotrexate and ciclosporin for moderate to severe plaque psoriasis had been performed. OBJECTIVES: To compare the effectiveness, quality of life and side-effects of methotrexate and ciclosporin treatments in a context reflecting normal clinical practice. METHODS: Eighty-four patients with moderate to severe plaque psoriasis were randomized to treatment with methotrexate or ciclosporin for 12 weeks. The primary outcome was the Psoriasis Area and Severity Index (PASI). The secondary outcome was quality of life, measured by the Dermatology Life Quality Index (DLQI) and the 36-item Short Form Health Survey (SF-36). A visual analogue scale (VAS) was used for patients' assessment. RESULTS: Sixty-eight patients started treatment and were included in the analysis. Dropout before initiation of treatment was higher in the ciclosporin group. Mean PASI change from baseline at 12 weeks was 58% in the methotrexate group and 72% in the ciclosporin group, showing ciclosporin to be more effective than methotrexate. Improvement of the VAS score was higher in the ciclosporin group. The methotrexate group showed a greater improvement in the subscale Physical Functioning of the SF-36. No significant difference between the groups was found for DLQI. CONCLUSIONS: Treatment with methotrexate or ciclosporin for chronic plaque psoriasis brings satisfactory disease control, improved quality of life and tolerable side-effects. A statistically significant difference in effectiveness between treatment groups was recorded, showing ciclosporin to be more effective than methotrexate in a short-term perspective.     

Efficacy of a day-care program in the treatment of psoriasis

BACKGROUND: Few data exist documenting the effectiveness of psoriasis day-care treatment programs (PDTPs) using standardized efficacy measurements. OBJECTIVES: We sought to analyze the efficacy of a PDTP using the Psoriasis Area and Severity Index (PASI). METHODS: A retrospective review was performed on 132 patients treated at our PDTP. Sufficient data existed to permit PASI analysis using a simplified method for a representative subgroup of 64 patients, who formed the study population. Patients received phototherapy and topical treatments over 2 weeks. The outcome measures included a baseline and day 11 PASI, a physician global assessment (PGA), and adverse events reported by the patients. RESULTS: Mean baseline PASI was 13.6 (N = 64), with a 59.6% reduction by day 11. A PASI reduction of > or = 50% was seen in 75% of patients, with 30% of patients achieving > or = 75% reduction of PASI. Day 11 PGA demonstrated a 69.9% improvement. CONCLUSION: With a reduction in PASI of 59.6% at 11 days, our PDTP, with phototherapy and topical agents, seems to be a rapid and effective therapy for psoriasis.     

The efficacy of narrowband ultraviolet B phototherapy in psoriasis using objective and subjective outcome measures

The efficacy of narrowband ultraviolet B (UVB) was assessed in 100 consecutive patients with psoriasis by quantifying disease severity using objective (Psoriasis Area and Severity Index, PASI and Dermatologists Global Assessment, DGA) and subjective (Psoriasis Disability Index, PDI) measures. The median pretreatment PASI, DGA and PDI were 5.7 (interquartile range, IQR 4.5-8.35), 7 (IQR 6-9) and 42 (IQR 29-63.5), respectively. At 3 month follow-up, the PASI, DGA and PDI had fallen to 2.7 (IQR 1.1-3.5), 3 (IQR 2-5) and 30 (IQR 21-50.5), respectively (P < 0.001). A small group of patients continued to score highly on their PDI despite being clinically clear or having minimal disease, possibly representing chronic disability behaviour. Patients exhibiting this may require more intensive supervision. In most patients, symptoms of itch and pain improved or disappeared (70% and 75%, respectively). Side-effects were reported in 18%. Narrowband UVB phototherapy is safe and effective for psoriasis. Symptoms and subjective quality of life measures improved significantly. Both objective and subjective measures should be used when evaluating the efficacy of a treatment for psoriasis.     

Positive effect of modified Goeckerman regimen on quality of life and psychosocial distress in moderate and severe psoriasis

Psoriasis is a chronic inflammatory skin disease with a profound effect on quality of life and psychosocial stress. The relationship between clinical improvement and psycho-social impact after treatment is complex. The objective of this study was to compare changes in quality of life and psychosocial distress, and overall cost-effectiveness, in patients with psoriasis receiving the modified Goeckerman regimen (UV irradiation and coal tar) with those receiving conventional treatment. Patients with moderate/severe psoriasis receiving the Goeckerman regimen were followed from admission to discharge. Clinical severity, was evaluated weekly using the Psoriasis Area and Severity Index (PASI). Psoriasis Disability Index (PDI) and Hospital Anxiety and Depression Scale (HADS) questionnaires were applied at admission and one month after discharge. Thirty-six patients with psoriasis receiving conventional treatment and 48 patients receiving the Goeckerman regimen were recruited to the study. The mean PASI score in the Goeckerman group decreased from 27.1 to 6.9 and PDI scores decreased from 25.3 to 13.8. HADS scores for anxiety and depression decreased significantly from 9.8 to 6.3 and 9.1 to 6.8, respectively. In comparison with conventional therapy, the modified Goeckerman regime showed similar clinical efficacy, with additional benefits in improving overall quality of life and psychosocial distress in patients with moderate/severe psoriasis, and more cost-effectiveness.     

Placebo response in relation to clinical trial design: a systematic review and meta-analysis of randomized controlled trials for determining biologic efficacy in psoriasis treatment

There is a need to better define how the efficacy of investigational drugs is affected by study design, implementation, and placebo responses in randomized controlled trials. The improvements observed in placebo groups within trials examining psoriasis treatments may be partially due to study design and implementation. We conducted a systematic review of randomized placebo-controlled trials assessing the efficacy of biologics in the treatment of psoriasis and psoriatic arthritis to evaluate rates of placebo and active drug responders to determine specific factors within study design that may contribute to placebo responses. We included randomized, placebo-controlled trials of etanercept, infliximab, adalimumab, golimumab, ustekinumab, alefacept, and efalizumab that utilized Psoriasis Area Severity Index as an outcomes measure. We compared the rates of the placebo treatment arm versus the active drug arm achieving 75?% improvement of Psoriasis Area Severity Index. 31 trials involving 8285 active treatment and 3999 placebo patients were included. Rates of placebo responders (4.14?%) were significantly lower than active drug responders (48.4?%). The overall odds ratio calculated was 23.94 (p?<?0.0001, 95?% CI 16.02–35.76). Binomial regression models showed that treatment indication, randomization fraction, a PASI inclusion requirement, and the time period of outcomes measure documentation affect placebo responses. Placebo responses seen in randomized controlled trials evaluating biologics in the treatment of psoriasis are not likely due to a physiologic mechanism, but may be secondary to chronic disease course and factors of clinical trial design and implementation.     

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.     

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

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