Body weight increment in patients treated with infliximab for plaque psoriasis

Background Psoriasis is frequently associated with overweight and obesity. Anti‐TNF‐α therapies are effective in the treatment of psoriasis. TNF‐α is highly involved in body weight regulation. Objective Our objective was to evaluate the increase in weight throughout the treatment with infliximab and the association of weight gain with the body mass index (BMI). Methods Thirty‐five patients affected with severe plaque psoriasis receiving infliximab were included. A control group consisted of 16 patients affected with severe plaque psoriasis and treated with cyclosporine, methotrexate, or acitretin. Assessment of PASI score, body weight and BMI were performed at a 1 and 3‐year follow‐up. Results We observed a body weight increment of 2.5 ± 4.4 kg (mean ± SD) (i.e. + 3.6% of baseline) and 0.1 ± 5 kg (i.e. + 1.2%) in patients treated with infliximab and the control group, respectively (P = 0.046), after 1 year of treatment. After 3 years of infliximab administration, weight gain was 4.8 ± 5 kg (n = 16) (i.e. + 6%) (P = 0.005). Moreover, as classified by BMI, normal weight patients experienced a 4 ± 3.7 kg weight gain (i.e. + 6%) whereas overweight and obese patients had gained 1.3 ± 4.8 kg (i.e. + 1.2%) (P = 0.039) after 1 year of anti‐TNF‐α therapy. Percentual changes in body weight were larger in normal weight patients at baseline than in overweight/obese counterparts (P = 0.0149). Conclusion All patients, including normal weight patients, should receive a dietary intervention.     

Practical experience of ustekinumab in the treatment of psoriasis: experience from a multicentre, retrospective case cohort study across the U.K. and Ireland

Background There are limited data on the use of ustekinumab outside of clinical trials. Objectives To assess the efficacy and safety of ustekinumab in patients with severe psoriasis attending 10 dermatology centres in the U.K. and Ireland. Methods A retrospective case‐note review of 129 patients with psoriasis treated with ustekinumab. Results Baseline Psoriasis Area and Severity Index (PASI) was 22·9 ± 10·1 (mean ± SD). After 16 weeks of treatment with ustekinumab PASI 75 (75% reduction in PASI) was observed in 63·0% (n = 80/127) of patients, although four patients required concomitant therapy at the 16‐week time point. Previous biologic use did show a small, non‐significant trend towards treatment failure. A PASI 75 response was seen in 29·4% (n = 5/17) of individuals weighing 90–100 kg and treated with the standard 45 mg ustekinumab dose compared with PASI 75 of 70·3%, 71·4%, 75·0% and 55·6% for weight groups < 80, 80–90, 100–110 and > 110 kg, respectively (P = 0·024). Ustekinumab therapy was well tolerated; serious adverse events were observed in 2·3% (n = 3/129) of patients. Conclusions Ustekinumab is a novel biologic agent for psoriasis. When used in everyday clinical practice it demonstrates high levels of short‐term therapeutic efficacy with an acceptable short‐term safety profile.     

Treatment with 311-nm ultraviolet B enhanced response of psoriatic lesions in ustekinumab-treated patients: a randomized intraindividual trial

Background Treatment with the interleukin‐12/23 antibody ustekinumab produces a satisfactory response [i.e. 75% reduction in Psoriasis Area and Severity Index (PASI) compared with baseline (PASI 75)] in the majority of patients with moderate to severe chronic plaque‐type psoriasis. Objectives To determine whether concomitant 311‐nm ultraviolet (UV) B therapy can further enhance the response in patients with psoriasis treated with ustekinumab. Methods Ten patients (five women and five men; mean age 58 years, range 48–66) with moderate to severe plaque‐type psoriasis were treated with ustekinumab at a standard dosage of 45 or 90 mg subcutaneously depending on body weight (below or above 100 kg) at weeks 0 and 4. Within 2 days after ustekinumab initiation, the minimal erythemal dose (MED) was determined and suberythemal MED 311‐nm UVB‐based phototherapy was thereafter administered to one randomly selected body half (left or right, excluding the head) three times weekly for 6 weeks. Treatment response was monitored weekly in terms of half‐body PASI. Results Nine patients completed the study. Analysis of their data showed that 311‐nm UVB significantly accelerated the therapeutic response. At baseline (i.e. start of 311‐nm UVB therapy), the mean PASI was similar in both irradiated and unirradiated body halves (13·6 vs. 13·3). At week 6, however, it was lower on irradiated body halves (2·5 vs. 6·1). This difference of 3·6 (95% confidence interval 1·3–5) was statistically significant and corresponded to an overall mean PASI reduction from baseline of 82% vs. 54%, respectively. At week 6, PASI 75 was achieved significantly more often on UV‐irradiated body halves than on unirradiated body halves [7/9 patients (78%) vs. 1/9 (11%)] (McNemar test, P = 0·007). At week 12, this synergistic effect of 311‐nm UVB was still apparent although not significantly so. Conclusions Treatment with 311‐nm UVB accelerates the clearance of psoriatic lesions in ustekinumab‐treated patients.     

Impact of obesity on the efficacy of ustekinumab in Japanese patients with psoriasis: a retrospective cohort study of 111 patients

Obesity is thought to be involved in the pathogenesis of psoriasis, although its impact on the therapeutic response to systemic treatments remains unclear. The aim of this study was to examine the association of body mass index (BMI) with the efficacy of ustekinumab in Japanese patients with psoriasis. Clinical data from a cohort of 111 Japanese patients treated with ustekinumab 45 mg between July 2011 and March 2014 were retrospectively evaluated. The measured outcome was improvement in the psoriasis area and severity index (PASI) score at week 16. Patients with BMI ≥ 25 and BMI < 25 had comparable rates of ≥50 and 75 % improvement in PASI (PASI-50 and PASI-75, respectively), whereas patients with BMI ≥ 25 had significantly lower PASI-90 and PASI-100 response rates. Patients with BMI ≥ 25 also showed significantly lower percent reduction in PASI than those with BMI < 25 at week 16 (85 vs. 74 %, P < 0.004). BMI was negatively correlated with percent reduction in PASI, whereas body weight was not. These results show that a higher BMI, but not body weight, is associated with lower effectiveness of ustekinumab for psoriasis. BMI ≥ 25 could therefore be a negative predictor of achieving PASI-90 and PASI-100 in patients with psoriasis when starting ustekinumab.     

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.     

Serum chemerin is increased in patients with chronic plaque psoriasis and normalizes following treatment with infliximab

Background Chronic plaque psoriasis is associated with obesity, which is a metabolic and inflammatory disorder. Adipokines are involved in the pathogenesis of psoriasis and they are biomarkers of obesity‐related inflammation. Objectives To measure serum adipokines in patients with chronic plaque psoriasis treated with infliximab. Methods Serum levels of chemerin, resistin, visfatin, C‐reactive protein (CRP), lipids, glycaemia and liver enzymes were measured in 40 patients with psoriasis and 40 controls matched by age, sex and body mass index (BMI). Adipokines were measured at baseline and after 2–12 months of treatment with infliximab 5 mg kg^?1. Results At baseline, levels of chemerin (195·9 ± 48·5 vs. 145·6 ± 27·1 ng mL^?1), resistin (2·03 ± 0·9 vs. 1·4 ± 0·5 ng mL^?1) and CRP (5·5 ± 7·3 vs. 1·9 ± 4·4 mg L^?1) were higher (P < 0·01) in patients with psoriasis compared with controls. Psoriasis was associated with elevated chemerin level independently of age, sex, BMI and levels of cholesterol and triglycerides. Chemerin was linearly correlated to CRP (r = 0·4, P = 0·01) and resistin (r = 0·3, P = 0·01). Chemerin levels were higher in patients affected by psoriatic arthritis than in patients with psoriasis without arthritis (195·5 ± 49·1 vs. 158·1 ± 37·5 ng mL^?1, P = 0·01). After 2 months of infliximab treatment a significant reduction of chemerin, resistin and CRP levels was observed. Conclusions Patients with psoriasis have higher blood levels of adipokines, which normalize during therapy with infliximab. Whether this reduction is a direct effect of infliximab or secondary to a reduction of inflammation should be further investigated.     

Effects of tumor necrosis factor‐α, interleukin‐23 and interleukin‐17A inhibitors on bodyweight and body mass index in patients with psoriasis

Treatment with tumor necrosis factor‐α inhibitors has been reported to cause weight gain in patients with psoriasis; however, limited information is available in terms of the effects of interleukin (IL)‐23 and IL‐17A inhibitors on bodyweight (BW) in patients with psoriasis. This study aimed to investigate the effects of infliximab, ustekinumab and secukinumab on BW and body mass index (BMI) in patients with psoriasis. We retrospectively examined changes in BW and BMI among patients treated with these biologics at our hospital. At baseline, no significant differences in BW and BMI were observed among the patients treated with infliximab (n = 18), ustekinumab (n = 30) or secukinumab (n = 20). After 7 months of the therapy, significant increases in mean BW (from 71.4 to 74.3 kg) and mean BMI (from 24.7 to 25.7) were observed in the patients treated with infliximab, whereas no significant changes were observed in those treated with ustekinumab (BW, from 70.3 to 70.1 kg; BMI, from 25.4 to 25.3) or secukinumab (BW, from 69.0 to 68.9 kg; BMI, from 25.2 to 25.2). There were no differences in the proportion of the patients who showed 75% or more improvement in the Psoriasis Area and Severity Index among the three groups. These results suggest that infliximab increases BW in the patients with psoriasis, whereas ustekinumab and secukinumab do not affect the BW in these patients.     

Infliximab treatment results in significant improvement in the quality of life of patients with severe psoriasis: a double-blind placebo-controlled trial

Background Psoriasis is a chronic disease that significantly diminishes the health‐related quality of life (HRQOL). Infliximab is a chimeric, tumour necrosis factor α monoclonal antibody that has been shown to improve the signs and symptoms of plaque psoriasis. Objectives The objective of this study was to evaluate the effect of infliximab induction therapy on the HRQOL of patients with severe plaque psoriasis. Methods In this double‐blind, placebo‐controlled trial, 249 patients were randomly assigned to receive intravenous infusions of 3 or 5 mg kg^?1 of infliximab or placebo and were treated at weeks 0, 2 and 6. Patients completed the Dermatology Life Quality Index (DLQI) at baseline and week 10. Results Infliximab induction therapy resulted in a substantial improvement in HRQOL. At week 10, patients in the infliximab 3‐ and 5‐mg kg^?1 groups showed a median percentage improvement in DLQI scores of 84·0% and 91·0%, respectively, compared with 0% in the placebo group (P < 0·001). The median decrease from baseline in DLQI score at week 10 was 8·0 and 10·0 for the 3 and 5 mg kg^?1 infliximab groups, respectively, compared with 0 in the placebo group (P < 0·001). Thirty‐three per cent and 40% of patients in the 3 and 5 mg kg^?1 infliximab groups, respectively, had a DLQI score of 0 at week 10, compared with 2% in the placebo group (P < 0·001). There was a strong correlation between the percentage change from baseline at week 10 in Psoriasis Area and Severity Index (PASI) scores and the percentage change in DLQI scores during the same period (Spearman's correlation, 0·61, P < 0·001). When the infliximab and placebo treatment groups were combined, patients with at least 75% improvement in PASI scores between baseline and week 10 had a greater mean improvement in DLQI scores (81%) than those with 50–75% improvement in PASI during the same period (60%). Conclusions Infliximab induction therapy resulted in significant improvement in HRQOL in patients with severe psoriasis.     

Efficacy of psoralen plus ultraviolet A therapy vs. biologics in moderate to severe chronic plaque psoriasis: retrospective data analysis of a patient registry

Background Few studies have directly compared the clinical efficacy of psoralen plus ultraviolet A (PUVA) vs. biologics in the treatment of psoriasis. Objectives To compare the clinical efficacy of PUVA and biologic therapies for psoriasis under daily life conditions. Methods Data from a psoriasis registry ( http://www.psoriasis‐therapieregister.at ) of 172 adult patients with moderate to severe chronic plaque psoriasis treated between 2003 and 2010 were analysed retrospectively. These patients had received oral PUVA [118 treatment courses including 5‐methoxypsoralen (5‐MOP; n = 32) and 8‐methoxypsoralen (8‐MOP; n = 86)] and/or biologic agents [130 treatment courses including adalimumab (n = 18), alefacept (n = 32), efalizumab (n = 17), etanercept (n = 38), infliximab (n = 7) and ustekinumab (n = 18)]. Treatment responses were analysed in terms of Psoriasis Area and Severity Index (PASI) improvement, including complete remission (CR) and reduction of PASI by at least 90% (PASI 90) or 75% (PASI 75), at treatment completion for PUVA (median time 10·3 and 9·2 weeks, for 8‐MOP and 5‐MOP, respectively) and at week 12 for biologics. Results Intention‐to‐treat–as observed CR, PASI 90 and PASI 75 rate was 22%, 69% and 86% for PUVA compared with 6%, 22% and 56% for adalimumab (P = 0·0034 by adapted Wilcoxon test), 3%, 3% and 25% for alefacept (P = 0·000000002), 6%, 6% and 59% for efalizumab (P = 0·000053), 6%, 29% and 39% for etanercept (P = 0·0000086), 29%, 71% and 100% for infliximab (P = 0·36) and 6%, 39% and 67% for ustekinumab (P = 0·028). When applying a more conservative post‐hoc modified worst‐case scenario analysis, with CR of 15%, PASI 90 of 58% and PASI 75 of 69%, PUVA was superior only to alefacept (P = 0·000013), efalizumab (P = 0·015) and etanercept (P = 0·0037). There were no statistically significant differences in PASI reduction rates between PUVA and infliximab. Conclusions Retrospective analysis of registry data revealed that the primary efficacy of PUVA was superior to that of certain biologics. Prospective head‐to‐head studies of PUVA and biologics are warranted to confirm these observations.     

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.     

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

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

Ustekinumab improves health-related quality of life in patients with moderate-to-severe psoriasis: results from the PHOENIX 1 trial

Background PHOENIX 1 was a phase III, randomized, double‐blind, placebo‐controlled study that demonstrated the long‐term efficacy and safety of ustekinumab in patients with moderate‐to‐severe psoriasis. Objectives To assess the effect of ustekinumab maintenance therapy on health‐related quality of life (HRQoL) in PHOENIX 1 patients. Patients and methods Patients (n = 766) were randomized to receive ustekinumab 45 mg (n = 255) or 90 mg (n = 256) at weeks 0 and 4 and every 12 weeks thereafter, or placebo (n = 255) at weeks 0 and 4 with crossover to ustekinumab at week 12. Ustekinumab‐randomized patients achieving at least 75% improvement in Psoriasis Area and Severity Index (PASI) 75 at weeks 28 and 40 were re‐randomized at week 40 to continue ustekinumab or be withdrawn until loss of therapeutic effect. HRQoL was assessed using the SF‐36 and Dermatology Life Quality Index (DLQI). Results At baseline, more than 97% had a DLQI > 1 and the average DLQI was > 10, indicating a significant impact on patients’ HRQoL. Significantly greater proportions of patients receiving ustekinumab 45 and 90 mg achieved a normalized DLQI score (≤ 1) compared with placebo (53·2%, 52·4% and 6·0%, respectively, both P < 0·001) at week 12 and achieved a clinically meaningful improvement (increase of at least five points) in SF‐36 physical (23·1%, 33·7% and 15·6%) and mental (25·5%, 31·3% and 14·8%) component summary scores. At week 12, changes in individual DLQI and SF‐36 domains were significantly better in each ustekinumab group vs. placebo (P < 0·001). The magnitude of improvement across SF‐36 scales was greatest for the bodily pain and social functioning domains. Improvements in HRQoL were sustained with maintenance ustekinumab therapy through at least 1 year. Regression analysis showed that, after adjustment for improvement in PASI or Physician’s Global Assessment (PGA), ustekinumab‐treated patients demonstrated significant improvements in DLQI. Conclusions Ustekinumab improves HRQoL in patients with moderate‐to‐severe psoriasis. Patient‐reported outcomes measured a treatment effect beyond that indicated by clinical measures.     

Combining etanercept and acitretin in the therapy of chronic plaque psoriasis: a 24-week, randomized, controlled, investigator-blinded pilot trial

Background Combination treatments may increase efficacy while reducing dosages and side‐effects of individual agents. No randomized controlled trials have been published combining biologics with conventional agents for psoriasis. Objectives To investigate the efficacy and safety of the association of acitretin and etanercept in the treatment of moderate to severe chronic plaque psoriasis. Methods A 24‐week, randomized, controlled, investigator‐blinded pilot trial was conducted. Sixty adult patients with moderate to severe chronic plaque psoriasis were randomized into three groups to receive etanercept 25 mg twice weekly subcutaneously, oral acitretin 0·4 mg kg^?1 daily or etanercept 25 mg once weekly plus acitretin 0·4 mg kg^?1 daily. The primary end point was a 75% or greater improvement in Psoriasis Area and Severity Index (PASI) from baseline (PASI 75) at week 24. Results At week 24, PASI 75 response was achieved by 10 of 22 patients in the etanercept group (45%), six of 20 in the acitretin group (30%) and eight of 18 (44%) in the group treated with etanercept plus acitretin (P = 0·001 for both etanercept groups compared with acitretin alone). A 50% or greater improvement from baseline in PASI was achieved by 15 of 22 (68%), 10 of 20 (50%) and 12 of 18 (67%) patients, respectively (P = 0·001). The safety profiles of the three groups were similar. Conclusions A combined therapeutic regimen with etanercept 25 mg once weekly and acitretin 0·4 mg kg^?1 daily is as effective as etanercept 25 mg twice weekly, and more effective than acitretin alone. Although larger studies are needed to confirm these results, the etanercept/acitretin association could offer several advantages in the therapy of moderate to severe chronic plaque psoriasis.     

Treatment of severe,recalcitrant, chronic plaque psoriasis with fumaric acid esters: a prospective study

Background Fumaric acid esters (FAE) are used in Germany as a first‐line systemic treatment for chronic plaque psoriasis, with proven efficacy and low toxicity. Their use in the U.K. is variable, and they remain unlicensed. Consequently, efficacy and safety data from U.K. patients is limited and their place in the psoriasis treatment armamentarium is unclear. Objectives To examine the efficacy and safety of FAE in a prospective cohort of U.K. patients with severe, treatment‐recalcitrant, chronic plaque psoriasis. Methods A single‐centre, open, nonrandomized, prospective study was performed in a regional referral centre for patients with severe psoriasis. Outcomes were measured by the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), blood investigations and adverse events monitoring. Results Eighty patients were recruited. Fifty‐nine per cent were taking a concomitant oral antipsoriatic agent; 20% achieved a PASI‐50, 8% a PASI‐75 and 4% a PASI‐90 on intention‐to‐treat analysis at 3 months with an overall, statistically significant, reduction in PASI from 13·9 ± 9·0 to 11·3 ± 9·2 (P < 0·0001). At 3 months, lymphopenia was seen in 33% of the cohort with significantly lower counts in patients responsive to FAE (P = 0·008). In addition, by 3 months, 36% of concomitant antipsoriatic medication had been stopped and 25% of doses had been reduced without loss of disease control. Side‐effects (most commonly diarrhoea, abdominal pain and flushing) were reported by 74% of patients resulting in cessation of FAE in 36%. Conclusions FAE is a useful alternative treatment option in patients with severe, treatment‐resistant, chronic plaque psoriasis and can allow dose reduction, and subsequent cessation, of other, potentially more toxic agents.     

Plasma homocysteine and folate levels in patients with chronic plaque psoriasis

Background Hyperhomocysteinaemia is a well‐known risk factor for cardiovascular diseases. Patients with severe chronic plaque psoriasis have a higher risk of death due to arterial and/or venous thrombosis. Objectives To investigate the relationship among plasma homocysteine and folate levels and severity of chronic plaque psoriasis in a selected cohort of patients with psoriasis without known risk factors for acquired hyperhomocysteinaemia. Methods We performed a case–control study in 40 patients with chronic plaque psoriasis and 30 age‐ and sex‐matched healthy controls. Cases and controls were selected excluding individuals with conditions or diseases associated with acquired hyperhomocysteinaemia, and were also asked to stop alcohol and coffee consumption for 1 week before blood sampling. The plasma levels of homocysteine and folic acid were measured and were correlated with the severity of psoriasis (Psoriasis Area and Severity Index, PASI). Results Patients with psoriasis had plasma homocysteine levels higher than controls (mean ± SD 16·0 ± 5·6 vs. 10·4 ± 4·7 μmol L^?1; P < 0·001). Conversely, folic acid levels were lower in patients with psoriasis compared with controls (mean ± SD 3·6 ± 1·7 vs. 6·5 ± 1·7 nmol L^?1; P < 0·001). Plasma homocysteine levels in patients with psoriasis correlated directly with disease severity (PASI) and inversely with folic acid levels. Plasma folic acid levels were inversely correlated with the PASI. No abnormalities of plasma vitamin B₆ and B₁₂ were found. Conclusions Patients with psoriasis may have a tendency to hyperhomocysteinaemia, which may predispose to higher cardiovascular risk. Dietary modification of this risk factor appears relevant to the global management of patients with moderate to severe psoriasis.     

Efficacy and safety results from a phase III, randomized controlled trial comparing the safety and efficacy of briakinumab with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis

Background The tumour necrosis factor‐α antagonist etanercept and the interleukin (IL)‐12/23p40 antagonist ustekinumab have been shown to be effective psoriasis therapies. The IL‐12/23p40 antagonist briakinumab was shown to be effective psoriasis treatment in a phase II study. Objectives To assess the efficacy, safety and tolerability of briakinumab compared with etanercept and placebo in patients with moderate to severe psoriasis. Methods Three hundred and fifty patients were enrolled in this phase III, 12‐week study (M10‐315, NCT00710580) and randomized in the following 2:2:1 ratio: 139 patients received 200 mg briakinumab at weeks 0 and 4 followed by 100 mg briakinumab at week 8; 139 patients received 50 mg of etanercept twice weekly 3–4 days apart at weeks 0–11; 72 patients received placebo injections matching active treatment. The co ‐ primary efficacy endpoints were the proportion of patients achieving a Physician’s Global Assessment (PGA) of 0/1 at week 12, and the proportion of patients achieving a Psoriasis Area and Severity Index (PASI) 75 response at week 12. Results Of the briakinumab‐treated patients, 72·7% achieved a PGA of 0/1 at week 12 as compared with 29·5% of etanercept‐treated patients and 4·2% of placebo‐treated patients (P < 0·001, for both comparisons). Of the briakinumab‐treated patients, 80·6% achieved a PASI 75 response at week 12 as compared with 39·6% of etanercept‐treated and 6·9% of placebo‐treated patients (P < 0·001, for both comparisons). Serious adverse events were reported in two (1·4%) briakinumab‐treated patients, one (0·7%) etanercept‐treated patient and two (2·8%) placebo‐treated patients. Conclusions In patients with moderate to severe psoriasis, briakinumab had superior efficacy to both placebo and etanercept at 12 weeks as administered in this study.     

Impact of ustekinumab on health-related quality of life in Japanese patients with moderate-to-severe plaque psoriasis: Results from a randomized, double-blind, placebo-controlled phase 2 / 3 trial

This study evaluates the effect of ustekinumab on health‐related quality of life (HRQoL) in Japanese patients with moderate‐to‐severe plaque psoriasis through 64 weeks. A total of 158 patients were randomized to receive subcutaneous injections of ustekinumab 45 mg (n = 64) or 90 mg (n = 62) at weeks 0, 4, and every‐12‐weeks, or placebo (n = 32) with crossover to ustekinumab at week 12. Secondary study endpoints included change in Dermatology Life Quality Index (DLQI) at week 12. Other assessments included the 36‐item Short Form health survey to assess Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, and Psoriasis Disability Index (PDI), a psoriasis‐specific instrument to assess HRQoL. Baseline demographic and disease characteristics were similar across randomized treatment groups. Ustekinumab‐treated patients had significantly greater mean improvements in DLQI from baseline to week 12 (45 mg: 8.0 ± 6.5; 90 mg: 7.4 ± 6.5) than placebo‐treated patients (0.3 ± 5.3; P < 0.0001 for each), and these improvements were maintained through week 64. Also at week 12, significant improvements from baseline in PDI scores were observed in ustekinumab‐treated patients (45 mg: 8.6 ± 9.6; 90 mg: 12.0 ± 11.8) compared with placebo‐treated patients (?0.1 ± 4.2). Improvements in the PCS (45 mg: 7.8 ± 14.5; 90 mg: 5.1 ± 12.0) and MCS (45 mg: 5.3 ± 9.8; 90 mg: 5.8 ± 10.5) scores were also observed in ustekinumab‐treated patients at week 12. Placebo‐treated patients who crossed‐over to ustekinumab achieved improvements in HRQoL comparable to those observed in patients originally randomized to ustekinumab. Ustekinumab significantly improves HRQoL in Japanese patients with moderate‐to‐severe plaque psoriasis through week 64.     

Infliximab for the treatment of psoriasis in Greece: 4 years of clinical experience at a single centre

Background Infliximab, a chimeric monoclonal antibody, has been shown to be effective for moderate to severe psoriasis. Clinical experience with long‐term infliximab therapy for psoriasis is accumulating, and it is therefore important to share our experience with its use in real‐life clinical practice. Objectives To report our experience with infliximab (Remicade^®; Schering Plough, Kenilworth, NJ, U.S.A.) for the treatment of moderate to severe plaque psoriasis (and/or arthritis) from a single clinic in Greece. Patients and methods Between August 2004 and March 2008, 62 patients presenting to our clinic with moderate to severe psoriasis were treated with infliximab. Disease phenotype, clinical course, disease severity and adverse events were assessed throughout the treatment period. Results Infliximab resulted in a reduction of median Psoriasis Area and Severity Index (PASI) of 70% at week 6 and 84·4% at week 14. Nineteen patients who have completed 1 year on infliximab treatment experienced sustained efficacy with a median PASI improvement of 92·16% and a Physician’s Global Assessment (PGA) of ‘clear’ or ‘almost clear’, while nine patients have reached approximately 20 months of continuous therapy. All patients with psoriatic arthritis showed marked improvement in their clinical symptoms following the first infusion. Eight patients (12·9%) experienced adverse events that required discontinuation of treatment. There were no statistically significant differences in PASI and Dermatology Life Quality Index (DLQI) scores between patients with arthritis and those with only skin lesions, or between those who received methotrexate, either from the beginning or during infliximab therapy, and those who did not receive methotrexate at all. Selected patients of interest are discussed. Conclusions The above data confirm previous reports that treatment with infliximab is an efficacious and safe option for patients with moderate to severe plaque psoriasis (and/or arthritis). Long‐term follow‐up, continued pharmacovigilance, and controlled comparative studies will be required to fully evaluate its use in the treatment of psoriasis.     

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.     

Efficacy and safety of tofacitinib, an oral Janus kinase inhibitor, in the treatment of psoriasis: a Phase 2b randomized placebo-controlled dose-ranging study

Background Tofacitinib is a novel, oral Janus kinase inhibitor under investigation as a potential treatment for plaque psoriasis. Objectives This Phase 2b, 12‐week, dose‐ranging study (A3921047, NCT00678210) aimed to characterize the exposure–response, efficacy and safety of tofacitinib vs. placebo in patients with moderate‐to‐severe chronic plaque psoriasis. Methods One hundred and ninety‐seven patients were randomized. The primary endpoint was the proportion of patients achieving a ≥ 75% reduction in the Psoriasis Area and Severity Index (PASI 75) score at week 12. Results At week 12, PASI 75 response rates were significantly higher for all tofacitinib twice‐daily groups: 25·0% (2 mg; P < 0·001), 40·8% (5 mg; P < 0·0001) and 66·7% (15 mg; P < 0·0001), compared with placebo (2·0%). Significant increases in the proportion of PASI 75 responses were seen by week 4 and were maintained at week 12. Exposure–response over the 0–15 mg tofacitinib twice‐daily dose range was successfully characterized. PASI 50, PASI 90 and Physician’s Global Assessment response rates were also higher for tofacitinib vs. placebo. The most frequently reported adverse events (AEs) were infections and infestations: 22·4% (2 mg twice daily), 20·4% (5 mg twice daily), 36·7% (15 mg twice daily) and 32·0% (placebo). Discontinuations due to AEs were 6·0%, 2·0%, 4·1% and 6·1% of patients in the placebo, and 2, 5 and 15 mg twice‐daily tofacitinib groups, respectively. Dose‐dependent increases from baseline in mean serum high‐density lipoprotein, low‐density lipoprotein and total cholesterol, and decreases in haemoglobin and neutrophils were observed. Conclusion Short‐term treatment with oral tofacitinib results in significant clinical improvement in patients with moderate‐to‐severe plaque psoriasis and is generally well tolerated.