Efficacy and safety of systemic methotrexate in two fixed doses of 10 mg or 25 mg orally once weekly in adult patients with severe plaque-type psoriasis: a prospective, randomized, double-blind, dose-ranging study

Background. Methotrexate (MTX) is the ‘gold‐standard’ drug for the treatment of severe psoriasis. In the absence of any consensus on an optimum dose of MTX for psoriasis, there is wide variation in prescribing patterns between dermatologists, resulting in variable or delayed therapeutic effects. Aim. To identify the most effective fixed single weekly dose of oral MTX with acceptable side‐effects in the treatment of severe plaque‐type psoriasis. Methods. This was a prospective, randomized, double‐blind, parallel‐group, dose‐ranging study, which enrolled 60 patients of both genders (aged 18–62 years) with severe chronic plaque‐type psoriasis. Patients were randomly assigned to one of two groups: group A was treated with MTX 10 mg once weekly, and group B was treated with 25 mg MTX once weekly. The main outcome measure was change in Psoriasis Area and Severity Index (PASI) between the two groups from baseline to 12 weeks. Results. Of the 60 patients, 51 (85%) completed the 12‐week study. At the end of the study, 24 patients (92.3%) in the MTX 25 mg group had achieved a 75% reduction in PASI (PASI 75) from baseline, compared with 18 patients (72%) in the MTX 10 mg group (P > 0.05). Mean time in weeks to achieve PASI 75 was significantly shorter in the MTX 25 mg group (7.92 ± 1.91) than in the MTX 10 mg group (9.47 ± 2.29) (P < 0.05). In addition, 20 patients (69%) in the MTX 25 mg group achieved 100% reduction in PASI compared with 9 patients (30%) in the MTX 10 mg group within 12 weeks of the study period (P < 0.01). Adverse effects were generally mild, and were noted in 43.1% of the 51 patients who completed the study, with no significant difference in frequency between the two groups, although they were less severe in the 10 mg group. Conclusions. MTX 25 mg is an effective dose as monotherapy for the treatment of severe psoriasis, whereas the 10 mg dose is slow to act and less effective, but has a less severe side‐effect profile.     

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.     

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 mycophenolate mofetil vs. methotrexate for the treatment of chronic plaque psoriasis

Background Methotrexate (MTX) is a well‐known systemic drug for moderate to severe chronic plaque psoriasis. Recently, mycophenolate mofetil (MMF) has been recommended for psoriasis. Objective To compare the efficacy and safety of MMF vs. MTX for the treatment of chronic plaque psoriasis. Methods Thirty‐eight consecutive patients with Psoriasis Area and Severity Index (PASI) >10 were randomly assigned for 12 weeks of treatment with either MTX (18 patients; initial dose, 7.5 mg/week) or MMF (20 patients; dose; 2 g/day) and were followed for 12 weeks after discontinuing the treatment. The differences between the two groups were analysed at the end of treatment and follow‐up comparing with baseline values. Results After 12 weeks of treatment, the mean ± SD score for the PASI decreased from 16.46 ± 5.29 at baseline to 3.17 ± 2.35 among 15 patients treated with MTX, whereas the score decreased from 17.43 ± 7.42 to 3.97 ± 5.95 among 17 patients treated with MMF (P > 0.05). Twelve weeks after discontinuing the treatment, the scores were 4.77 ± 3.52 and 5.94 ± 4.27, respectively (P > 0.05). PASI ‐75 were achieved in 58.8% of patients in MMF group and 73.3% in MTX group (P > 0.05). Three months after discontinuing the treatment, PASI‐75 remained in 33.3% of patients in MMF and 53.3% of MTX group (P > 0.05). Both drugs were well tolerated and side‐effects were minor and transient. Conclusions No significant differences in efficacy were found between MTX and MMF groups. MMF may represent a good alternative for the treatment of psoriasis in patients who are unable to take MTX or other available drugs due to contraindication or toxicity.     

A randomized trial of etanercept as monotherapy for psoriasis

OBJECTIVE: To determine safety and efficacy of monotherapy with etanercept. DESIGN: Randomized, double-blind, placebo-controlled, multicenter study. SETTING: Outpatient, ambulatory; private practice and university dermatology research centers. PATIENTS: Patients aged at least 18 years, with plaque psoriasis involving 10% or more of body surface area; 148 were screened and 112 were randomly assigned to treatment groups and received study drug. INTERVENTIONS: Patients received placebo or etanercept, 25 mg, subcutaneously twice a week for 24 weeks. Other psoriasis therapies were limited during the study. MAIN OUTCOME MEASURES: Safety measurements included tracking of adverse events and laboratory values. Efficacy was evaluated using the Psoriasis Area and Severity Index (PASI); the primary end point was a 75% improvement in PASI. Other efficacy measurements included patient and physician global assessments and quality-of-life measures. RESULTS: After 12 weeks of treatment, 17 (30%) of the 57 etanercept-treated patients and 1 (2%) of the 55 placebo-treated patients had achieved PASI 75%, and after 24 weeks, 32 (56%) of etanercept-treated patients and 3 (5%) of placebo-treated patients had reached this level (P<.001 for both time points). By 24 weeks, psoriasis was clear or minimal by physician's global assessment in more than 50% of patients who received etanercept. Treatment failure (PASI response <50) occurred in 23% of patients at week 24. All other measures confirmed the efficacy of etanercept. Adverse events were similar among etanercept and placebo groups. CONCLUSION: Etanercept monotherapy provided significant benefit to patients with psoriasis and had a favorable safety profile.     

Topical calcipotriol plus oral fumaric acid is more effective and faster acting than oral fumaric acid monotherapy in the treatment of severe chronic plaque psoriasis vulgaris

BACKGROUND: Calcipotriol is an established topical therapy for psoriasis vulgaris. OBJECTIVE: This study aimed to investigate whether the addition of calcipotriol to fumaric acid ester (FAE) monotherapy had an additive efficacy and an FAE-sparing effect in patients with severe plaque psoriasis. METHODS: This multicentre, randomised, double-blind, vehicle-controlled study included 143 patients for up to 13 weeks treatment. Group A received FAE tablets (Fumaderm) with an increasing daily dosage from 105 to 1,075 mg + ointment vehicle. Group B received FAE tablets + calcipotriol ointment (50 microg/g). Ointments were applied twice daily. Clinical response was assessed using percentage changes in the Psoriasis Area and Severity Index (PASI), from baseline to treatment end. RESULTS: The mean percentage change in the PASI was -76.1% in group B and -51.9% in group A, the difference between treatments was -24.2% (95% CI from -34.2 to -14.2%; p < 0.001). Group B responded more rapidly to treatment. Investigators' and patients' overall efficacy assessments were significantly more favourable for group B (p < or = 0.001). Group B was prescribed less FAE than group A. This difference was greatest at the last visit (mean daily dose 529 and 685 mg, respectively; p = 0.006). Overall adverse events in the two groups were similar. CONCLUSION: This study shows that the combination of calcipotriol and FAEs is significantly more effective and faster acting than FAE monotherapy in the treatment of severe plaque psoriasis. The combination has a slight FEA-sparing effect and therefore a superior benefit/risk ratio.     

Safety of efalizumab in adults with chronic moderate to severe plaque psoriasis: a phase IIIb, randomized, controlled trial

Background To provide safety data for efalizumab, a recombinant humanized monoclonal IgG₁ antibody, in adults with chronic plaque psoriasis. Methods A 12‐week, Phase IIIb, randomized, double‐blind, parallel‐group, placebo‐controlled trial. At 58 study sites in the USA and Canada, 686 patients with moderate to severe chronic plaque psoriasis received an initial conditioning dose of efalizumab 0.7 mg/kg subcutaneously (SC) followed by either 11 weekly doses of efalizumab 1 mg/kg SC or matching placebo. Main outcome measures were safety and tolerability outcomes (primary) and efficacy outcomes (secondary). Results During 12 weeks of therapy with efalizumab or placebo, the incidence of clinical adverse events was 82.2% and 72.9%, respectively; the incidence of serious adverse events was 1.8% and 3.4%, respectively; and the incidence of nonserious adverse events leading to withdrawal was 1.8% and 1.7%, respectively. In the efalizumab group, there were no clinically significant changes in vital signs or laboratory parameters and no evidence of end‐organ toxicities. A significantly higher proportion of patients receiving efalizumab than those receiving placebo achieved ≥ 75% improvement in the Psoriasis Area and Severity Index (PASI) (P < 0.001), ≥ 50% improvement in PASI (P < 0.001), and a static Physician's Global Assessment rating of Minimal or Clear (P < 0.001). The mean improvement in the Psoriasis Symptom Assessment was significantly greater in the efalizumab group (P < 0.001). Conclusions Efalizumab treatment SC for 12 weeks was safe, well tolerated, and effective in patients with moderate to severe chronic plaque psoriasis.     

Efficacy of oral methotrexate (MTX) monotherapy vs oral MTX plus narrowband ultraviolet light B phototherapy in palmoplantar psoriasis

Palmoplantar psoriasis (PPP) is a chronic, inflammatory dermatosis of the palms and/or soles with significant morbidity. It is notoriously difficult to treat and unresponsive to traditional topical agents. We aim to compare the effect of oral methotrexate (MTX) monotherapy vs MTX plus narrowband ultraviolet light B (NB‐UVB) in the treatment of recalcitrant PPP. This was a comparative clinical trial involving 90 patients of PPP. Eligible patients were randomly assigned to one of the two treatment groups. We aim patients in group A received 10 mg oral MTX weekly, and patients in group B received oral MTX 10 mg weekly and NB‐UVB sessions twice weekly for 12 weeks. There was a statistically significant difference in reduction of modified PPP Area Severity Index (m‐PPPASI) of patients in MTX plus NB‐UVB at week 12. The mean m‐PPPASI at week 12 was 3.66 ± 2.11 in MTX plus NB‐UVB group and 6.51 ± 2.04 in MTX only group (P < .001). Marked improvement (m‐PPPASI 75) was achieved in 20 (44.44%) patients in MTX plus NB‐UVB group compared with 6 (13.3%) in MTX monotherapy group (P < .001). Combination of MTX and NB‐UVB phototherapy helps to attain a better clinical response (reduction in m‐PPPASI score) than MTX monotherapy in the treatment of recalcitrant PPP.     

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.     

Long-term safety and efficacy of 50 mg of etanercept twice weekly in patients with psoriasis

OBJECTIVE: To evaluate the safety and efficacy of long-term treatment of psoriasis with etanercept, 50 mg twice weekly. DESIGN, SETTING, AND PATIENTS: A phase 3, randomized, double-blind trial with an open-label extension. A total of 618 adult patients with moderate to severe plaque psoriasis were studied at 39 medical centers in the United States and Canada from May 23, 2003, through June 22, 2005. INTERVENTIONS: Patients were randomized to receive placebo or etanercept for 12 weeks. Beginning with week 13, all patients (N=591) received etanercept. MAIN OUTCOME MEASURES: Exposure-adjusted adverse event rates were calculated. Efficacy measures included efficacy and patient global assessment of psoriasis. RESULTS: Exposure-adjusted rates of adverse events, serious adverse events, infections, and serious infections were similar for placebo and etanercept treatments. Nonneutralizing antibodies to etanercept, observed in 18.3% of patients, had no apparent effect on safety or efficacy. Patients responded within 2 weeks to etanercept, with statistically significant differences in the Psoriasis Area and Severity Index and Dermatology Life Quality Index between the etanercept and placebo groups at week 12. At week 24, after 12 weeks of open-label etanercept treatment, patients in the original placebo group had clinical benefits comparable to those of patients in the original etanercept group. As both groups progressed through the open-label period, the Psoriasis Area and Severity Index response peaked at week 48. At week 96, 51.6% of the original placebo-treated patients and 51.1% of the original etanercept-treated patients had improvements from baseline in the Psoriasis Area and Severity Index of at least 75%. CONCLUSIONS: Extended exposure to 50 mg of etanercept twice weekly resulted in exposure-adjusted rates of adverse events and infections similar to those in patients receiving placebo. Improvements in physician- and patient-reported measures of psoriasis severity were observed for up to 96 weeks of continuous etanercept therapy. Trial Registration clinicaltrials.gov Identifier NCT00111449.     

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 ixekizumab treatment for Japanese patients with moderate to severe plaque psoriasis,erythrodermic psoriasis and generalized pustular psoriasis: Results from a 52‐week,open‐label,phase 3 study (UNCOVER‐J)

Psoriasis, a chronic, immune‐mediated skin disease characterized by red, scaly plaques, affects approximately 0.3% of the population in Japan. The aim of this open‐label study was to evaluate the long‐term efficacy and safety of ixekizumab, a humanized, anti‐interleukin‐17A monoclonal antibody, in Japanese patients with plaque psoriasis (n = 78, including 11 psoriatic arthritis), erythrodermic psoriasis (n = 8) and generalized pustular psoriasis (n = 5). Ixekizumab was administrated s.c. at baseline (week 0, 160 mg), from weeks 2 to 12 (80 mg every 2 weeks), and from weeks 16 to 52 (80 mg every 4 weeks). At week 52, 92.3% of patients with plaque psoriasis achieved Psoriasis Area and Severity Index (PASI) 75, 80.8% achieved PASI 90, 48.7% achieved PASI 100, and 52.6% had remission of plaques (by static Physician Global Assessment, sPGA [0]). Difficult to treat areas of psoriasis (nail or scalp) also responded to ixekizumab. All patients with psoriatic arthritis who were assessed (5/5) achieved an American College of Rheumatology 20 response. Most patients with erythrodermic psoriasis or generalized pustular psoriasis responded to ixekizumab and the clinical outcome was maintained over 52 weeks (75% and 60% of patients achieved sPGA [0, 1] at week 52, respectively). Mostly mild or moderate treatment‐emergent adverse events were reported by 79 of 91 patients; the most common were nasopharyngitis, eczema, seborrheic dermatitis, urticaria and injection site reactions. In conclusion, 52‐week ixekizumab treatment was efficacious and well tolerated in Japanese patients with plaque psoriasis. Efficacy was also observed in patients with erythrodermic psoriasis, generalized pustular psoriasis and psoriatic arthritis.     

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.     

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

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

Efficacy and safety of acitretin in three fixed doses of 25, 35 and 50 mg in adult patients with severe plaque type psoriasis: a randomized,double blind,parallel group,dose ranging study

Background Acitretin is available for use in psoriasis since the late 1980s; however, there is no consensus on its optimum effective dose with acceptable side‐effects. Objective To evaluate the efficacy and safety of acitretin in three fixed doses in adult patients with severe plaque type psoriasis. Methods This was a randomized, double blind, parallel group, dose ranging study. The study included patients of either gender (age range, 18–65 years) with severe chronic plaque type psoriasis. Of the 80 patients screened, 61 were randomly assigned to three groups: group A – 20 patients (acitretin 25 mg/day), group B – 20 patients (acitretin 35 mg/day) and group C – 21 patients (acitretin 50 mg/day) for 12 weeks. Forty‐eight patients completed the study. The main outcome measure was change in Psoriasis Area Severity Index (PASI) score between the three groups from baseline to 12 weeks. Results After 12 weeks of therapy, the percentage reduction in the PASI score was 54%, 76% and 54% in acitretin 25, 35 and 50 mg/day group respectively. PASI 75 was achieved in 47%, 69% and 53% patients in acitretin 25, 35 and 50 mg/day groups respectively. The majority of adverse events were mucocutaneous, mild‐to‐moderate severity and dose dependent. Conclusions Acitretin 35 mg/day was observed to be more efficacious compared to 25 mg/day and 50 mg/day dosing, whereas its safety profile is better than 50 mg/day dosing in the management of severe plaque type psoriasis in adult patients.     

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.     

Assessment of methotrexate hepatotoxicity in psoriasis patients: a prospective evaluation of four serum fibrosis markers

Background Low‐dose oral methotrexate (MTX) is an effective immunosuppressive therapy for chronic plaque psoriasis. However, its use is hampered by the risk of liver fibrosis. Aim To compare the results of serial measurements of serum fibrosis markers during the remission‐induction phase of treatment with MTX to those of patients on biological therapy and long‐term MTX therapy (>2 years). Subjects and methods Serum concentrations of hyaluronic acid, N‐terminal propeptide of collagen type III (PIIINP) and the results of two multi‐test algorithms Fibrotest and Hepascore were evaluated in patients with chronic plaque psoriasis (N = 24, age: 28–79 years, baseline Psoriasis Area Severity Index PASI 13.5, range 2.2–33) at baseline and weeks 16 and 26 after the start of pharmacokinetically guided therapy with MTX (Group A). Patients on established therapy with biologics (N = 15, Group B) and long‐term MTX users (N = 10, Group C) with the mean baseline PASI scores of 0.9 and 1.2 were studied in parallel cohorts. Results At baseline, HA, Hepascore and PIIINP were correlated with PASI of Group A patients. At weeks 16 and 26, HA decreased by 48% and 40% (P < 0.001) and Hepascore by 31 (P < 0.01) and 20% (P < 0.05) respectively. PASI75 (≥75% improvement from baseline PASI) was observed in 76% of Group A patients by week 26 and the absolute decreases in PASI and both fibrosis markers were correlated (HA: r = 0.49, P = 0.018, Hepascore: r = 0.47, P = 0.022). In contrast, no significant within‐group differences were found in HA and Hepascore results of patients in the groups B and C. PIIINP and Fibrotest were stable in all groups. Conclusion The fibrosis markers hyaluronic acid and Hepascore (the multiple test algorithm which includes hyaluronic acid) are less liver specific and more prone to reflect psoriasis activity than PIIINP and Fibrotest.     

Efficacy,effectiveness and safety of fumaric acid esters in the treatment of psoriasis: a systematic review of randomized and observational studies

Fumaric acid esters (FAEs) are increasingly used as a systemic treatment for psoriasis, but there are still uncertainties regarding their suitability. The objective of this systematic review was to assess the evidence for the efficacy and safety of FAEs in psoriasis treatment. A systematic literature search was performed in seven databases up to 17 August 2015. Inclusion criteria were studies that reported clinical effects of FAEs in patients with psoriasis without restrictions in study design, language or publication date. Methodological quality of randomized controlled trials (RCTs) and overall level of quality were assessed using the Cochrane risk of bias tool and the Grading of Recommendation, Assessment, Development and Evaluation approach, respectively. A total of 68 articles were included. There were seven RCTs (total 449 patients) that had an unclear risk of bias and were too clinically heterogeneous to allow a meta‐analysis. Overall, mean Psoriasis Area and Severity Index decreased by 42–65% following 12–16 weeks of treatment. There were 37 observational studies (a total of 3457 patients) that supported the RCT findings, but most were uncontrolled with a high risk of bias. Commonly reported adverse events included gastrointestinal complaints and flushing, leading to treatment withdrawal in 6–40% of patients. Several case‐reports described rare adverse events, such as renal Fanconi syndrome and progressive multifocal leukoencephalopathy. There was a lack of studies focusing on long‐term use and comparisons with other treatments. This review concluded that there is low‐quality evidence to recommend the use of oral FAEs to treat plaque psoriasis in adult patients. Studies focusing on long‐term safety and comparison with systemic psoriasis treatments could lead to a better understanding of the role of FAEs as a treatment for psoriasis.     

Subcutaneous methotrexate versus oral form for the treatment and prophylaxis of chronic plaque psoriasis

Psoriasis is a common inflammatory skin disorder with complex pathomechanisms. Methotrexate (MTX) is an antiproliferative and immunomodulating agent that control psoriasis. The aim of this study is to compare the efficacy of MTX and tolerability to MTX by oral route versus subcutaneous (SC) route. Twenty‐eight cases were divided into two equal groups: Group I received a weekly dose of oral MTX and Group II received a weekly dose of SC MTX for 12 weeks. The starting dose was 7.5–10 mg and increased gradually by 2.5 mg every month till reaching 12.5–15 mg/week. Patients' clinical responses were evaluated according to Psoriasis Area and Severity Index (PASI) score. Results suggest that Group I patients showed reduction in PASI score of mean ± SD from 19 ± 7.4 before treatment to 11.2 ± 6.29 after treatment while Group II patients showed reduction from 23.4 ± 14.7 before treatment to 2.55 ± 2.6 after treatment with highly statistically significant difference between both groups. Clinical improvement was complete in 7.1% of Group I versus 57.1% of Group II. In conclusion, SC MTX has higher efficacy with lesser adverse effects and lower relapse rate when compared to oral form given by the same dose during the same duration.     

Efficacy and safety of adalimumab when added to inadequate therapy for the treatment of psoriasis: results of PRIDE, an open-label, multicentre, phase IIIb study

Background Adalimumab is an effective treatment for chronic plaque psoriasis. Objective To evaluate the safety and efficacy of adalimumab for psoriasis patients who did not adequately respond to prior psoriasis therapy. Methods PRIDE (an Open‐Label Access PR ogram to Evaluate the Safety and Effectiveness of Adalimumab When Added to I naDE quate Therapy for the Treatment of Psoriasis) was a multicentre, Phase IIIb study in Canada. Patients with active moderate‐to‐severe plaque psoriasis who failed to respond to, or were intolerant of, prior therapies received adalimumab 80 mg at Week 0 followed by adalimumab 40 mg every other week Weeks 1 through 23. The primary efficacy measure was PASI (Psoriasis Area Severity Index) 75 response at Week 16. Secondary efficacy measures included PASI 90/100 and percentage change from baseline PASI score. Adverse events (AEs) and serious AEs were recorded. Results A total of 203 patients were enrolled at 26 sites. Baseline characteristics were: male, 61.1%; mean age, 45.5 years; mean PASI score, 20.0; previous exposure to biologics, 38.4%. At Week 16, PASI 75/90/100 responses were achieved by 70.9%/49.3%/24.1% of patients, respectively. Mean percentage PASI score decrease from baseline to Week 16 was 79.5%. Mean percentage PASI improvement and response rates were maintained through Week 24. Nasopharyngitis and upper respiratory tract infection were the only AEs to occur in ≥5% of patients. Nine patients experienced serious AEs; four were considered possibly or probably related to adalimumab. Conclusion Adalimumab was safe, well‐tolerated and effective for treatment of active plaque psoriasis in patients who had not adequately responded to prior therapy.