The efficacy of methotrexate plus pioglitazone vs. methotrexate alone in the management of patients with plaque‐type psoriasis: a single‐blinded randomized controlled trial

Recently, thiazolidinediones have shown to be efficacious with a favorable safety profile when used in the treatment of chronic plaque‐type psoriasis. The aim of this study was to evaluate and compare the efficacy and safety of a combination of methotrexate plus pioglitazone and methotrexate alone in plaque‐type psoriasis. A total of 44 adult patients with plaque‐type psoriasis were included in the study. Patients were randomized to treatment with methotrexate alone (group A) or methotrexate plus pioglitazone (group B) for 16 weeks. The primary efficacy outcome measure was psoriasis area and severity index (PASI) score change between the study groups at week 16 relative to baseline. The secondary efficacy outcome measure was dermatology life quality index (DLQI) score change between the two groups at week 16 relative to baseline. The PASI 75 score was also measured. After 16 weeks of therapy, the percentage of reduction in the mean PASI score was 70.3% in group B and 60.2% in group A. PASI 75 was achieved in 14 patients (63.6%) in group B compared with two patients (9.1%) in group A within 16 weeks, which was significant (P < 0.001). At 16 weeks from the baseline, a 63.6% decrease in the mean DLQI score of group B was seen, while the decrease for group A was 56.9%. Pioglitazone enhances the therapeutic effect of methotrexate in plaque‐type psoriasis, as demonstrated by a reduction in the mean PASI scores. In terms of DLQI, there was no extra benefit by the addition of pioglitazone to methotrexate therapy.     

Left ventricular systolic asynchrony: an important sign for cardiac involvement in plaque‐type psoriasis

Psoriasis is associated with cardiovascular diseases (CVD). The purpose of this study was to evaluate the relationship between Left Ventricular (LV) asynchrony and psoriasis. Asynchrony was assessed in 31 patients with psoriasis without evidence of CVD and 25 healthy subjects. All the patients and controls were subjected to tissue synchronization imaging (TSI), and conventional and tissue Doppler echocardiography. The time to regional peak systolic tissue velocity (Ts) in LV by the six‐basal‐six‐midsegmental model was measured on ejection phase TSI images, and four TSI parameters of systolic asynchrony were computed. C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels in psoriatic patients were measured. All TSI parameters of LV asynchrony increased in psoriatic patients compared to the controls: the standard deviation (SD) of the 12 LV segments Ts (37.3 ± 14.8 vs. 24.6 ± 11.1, P = 0.002); the maximal difference in Ts between any two of the 12 LV segments (112.7 ± 39.8 vs. 83.1 ± 38.1, P = 0.01), the SD of the six basal LV segments (36.2 ± 17.3 vs. 23.2 ± 14.5, P = 0.008); and the maximal difference in Ts between any two of the six basal LV segments (91.3 ± 43.5 vs. 60.5 ± 37.3, P = 0.01). LV asynchrony was observed in 67.7% of psoriatic patients. Higher CRP (1.9 ± 1.3 vs. 0.92 ± 1.4, P = 0.04) and ESR (34.8 ± 17.3 vs. 20 ± 15.3, P = 0.03) levels were determined in patients with LV asynchrony. Regression analysis showed LV systolic asynchrony (P = 0.02), Tei index (P = 0.03), EF (P = 0.04), and E/A ratio (P = 0.04) were independently associated with psoriasis. LV asynchrony firstly described in patients with psoriasis may be an important finding of cardiac involvement in psoriasis.     

Targeted phototherapy of plaque‐type psoriasis using ultraviolet B–light‐emitting diodes

Background One of the major technological breakthroughs in the last decade is represented by the diversified medical applications of light‐emitting diodes (LEDs). LEDs emitting in the ultraviolet (UV) B spectrum might serve as a more convenient alternative for targeted delivery of phototherapy in inflammatory skin diseases such as psoriasis. Objectives We investigated the efficacy and safety of a new UVB‐LED phototherapeutic device in chronic plaque‐type psoriasis. Methods Twenty patients with stable plaque‐type psoriasis were enrolled into a prospective, right‐left comparative, open study. Symmetrical lesions located on extremities or trunk were chosen; one lesion was treated with the study device, whereas the other lesion served as an untreated control. Two treatment regimens were used in the study, one with an aggressive dose escalation similar to those used for outpatient treatment and one with slow increase in dose, similar to those used for treatment at home. Results Patients in both groups responded rapidly to the UVB‐LED therapy. Early disease resolution was observed in 11 patients (seven in the first group and four in the second group). Overall improvement at end of therapy was 93% in the high‐dose group and 84% in the low‐dose group. Four patients from the high‐dose group and five from the low‐dose group were still in remission at the 6‐month follow‐up visit. Conclusions These results suggest that this innovative UVB‐LED device is effective in the treatment of localized psoriasis and may be useful in other UV‐responsive skin diseases.     

Treatment of plaque psoriasis with an ointment formulation of the Janus kinase inhibitor,tofacitinib: a Phase 2b randomized clinical trial

Background

Most psoriasis patients have mild to moderate disease, commonly treated topically. Current topical agents have limited efficacy and undesirable side effects associated with long-term use. Tofacitinib is a small molecule Janus kinase inhibitor investigated for the topical treatment of psoriasis.

Methods

This was a 12-week, randomized, double-blind, parallel-group, vehicle-controlled Phase 2b study of tofacitinib ointment (2 % and 1 %) applied once (QD) or twice (BID) daily in adults with mild to moderate plaque psoriasis. Primary endpoint: proportion of patients with Calculated Physician’s Global Assessment (PGA-C) clear or almost clear and ≥2 grade improvement from baseline at Weeks 8 and 12. Secondary endpoints: proportion of patients with PGA-C clear or almost clear; proportion achieving Psoriasis Area and Severity Index 75 (PASI75) response; percent change from baseline in PASI and body surface area; change from baseline in Itch Severity Item (ISI). Adverse events (AEs) were monitored and clinical laboratory parameters measured.

Results

Overall, 435 patients were randomized and 430 patients received treatment. The proportion of patients with PGA-C clear or almost clear and ≥2 grade improvement from baseline at Week 8 was 18.6 % for 2 % tofacitinib QD (80 % confidence interval [CI] for difference from vehicle: 3.8, 18.2 %) and 22.5 % for 2 % tofacitinib BID (80 % CI: 3.1, 18.5 %); this was significantly higher vs vehicle for both dosage regimens. No significant difference vs vehicle was seen at Week 12. Significantly more patients achieved PGA-C clear or almost clear with 2 % tofacitinib QD and BID and 1 % tofacitinib QD (not BID) at Week 8, and with 2 % tofacitinib BID at Week 12. Pruritus was significantly reduced vs vehicle with 2 % and 1 % tofacitinib BID (starting Day 2), and 2 % tofacitinib QD (starting Day 3). Overall, 44.2 % of patients experienced AEs, 8.1 % experienced application site AEs, and 2.3 % experienced serious AEs. The highest incidence of AEs (including application site AEs) was in the vehicle QD group.

Conclusions

In adults with mild to moderate plaque psoriasis, 2 % tofacitinib ointment QD and BID showed greater efficacy than vehicle at Week 8, but not Week 12, with an acceptable safety and local tolerability profile.

Trial registration

NCT01831466 registered March 28, 2013.

     

D‐chiro‐inositol as a treatment in plaque psoriasis: A randomized placebo‐controlled clinical trial

Cyclitols are widely available natural sugars which do not exert toxic effects. Their anti‐inflammatory and antioxidant properties may be used in the treatment of psoriasis. The aim of this placebo‐controlled, double‐blind study was to evaluate the clinical effects of D‐chiro‐inositol (DCI) in mild plaque psoriasis (46 psoriatic patients and 10 healthy volunteers). Three stable psoriatic plaques were selected for evaluation in every patient. Different samples were applied on each lesion twice a day: vehiculum without an active agent, containing 1% DCI and 0.25% DCI. The lesions were assessed using the PSI, VAS scale, and the objective measurement of hydration, transepidermal water loss (TEWL), elasticity, and thickness (DermaLab Combo) at 0, 3, and 6 weeks. PSI and VAS were improved in all groups without significant statistical differences. 1% DCI sample presented the highest statistically significant increase in the hydration of 50%, but it was still significantly lower than in healthy controls. TEWL increased for 1% DCI, which was a statistically significant difference compared to 0.25% DCI and still higher than in controls. An improvement in elasticity was observed in all lesions—it was statistically significant for 1% DCI. The thickness of the lesion decreased for 1% DCI, but the change was not statistically significant. Subepidermal low‐echogenic band showed a decreasing tendency in all groups, but it was not statistically significant. Favorable 1% DCI sample results indicate that it may be used as an adjuvant to the local treatment of psoriasis.     

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.     

Costs and quality of life in patients with moderate to severe plaque‐type psoriasis in Germany: A multi‐center study

Background: This study evaluated costs, disease severity and health‐related quality of life (QoL) in patients with moderate to severe plaque‐type psoriasis. Patients and Methods: Patients with a ‘psoriasis area and severity index’ (PASI) > 12 and/or a body surface area (BSA) > 10 were enrolled in dermatological practices and hospital outpatient departments (n = 184) and the total costs of illness generated during the last 12 months were retrospectively calculated. QoL was assessed using the SF‐36 and the DLQI. Participants were stratified into three subgroups according to the treatment received during the 1 year documentation period; a) patients without and b) patients with phototherapy or standard systemic therapy, and c) patients who had failed, were intolerant or had contraindications to at least two standard systemic therapies. The study was performed before biologics became available for the treatment of psoriasis in Germany. Results: Included patients had severe skin symptoms (mean PASI 18.2) and a highly impaired QoL (mean DLQI 10.6). Total annual costs amounted to € 6,709. Patients belonging to subgroup C had the most severe skin symptoms (mean PASI 22.2), the lowest QoL (mean DLQI 12.6), the highest hospitalization rate and largest loss of productivity.These patients produced the highest total costs of 8.831 €/y. Conclusions: Patients who cannot (or can no longer) be adequately managed with standard treatments are characterized by high disease activity, high costs and reduced QoL. Improved treatment options particularly for these patients are medically necessary and appear economically sensible.     

Interleukin 10 treatment of psoriasis: clinical results of a phase 2 trial

OBJECTIVE: To determine the safety and clinical effects of interleukin 10 (IL-10) treatment of psoriasis. DESIGN AND METHODS: In an open-label phase 2 trial, 10 patients with psoriasis subcutaneously received recombinant human IL-10 over a 7-week period in a dosage of 8 microg/kg daily (n=5) or 20 microg/kg 3 times per week (n=5). Patients were followed up for an additional 5 weeks. RESULTS: The treatment was well tolerated. Antipsoriatic effects were found in all but 1 patient. A significant decrease of the psoriasis area and severity index by 55.3% +/- 11.5% (mean +/- SEM) was observed (P<.02). The antipsoriatic efficiency was confirmed by histological examination. Heterogeneity in the effectiveness was found among the patients, but seems to be independent of the dosage regimen. However, a tendency to a better response was found in the patients who received 20-microg/kg IL-10 3 times per week. Decreasing response in the delayed-type hypersensitivity reaction against recall antigens indicated immunosuppressive effects. Moderate effects on hematopoietic cells were observed. CONCLUSIONS: Our data suggest that IL-10 therapy for psoriasis is safe and possibly clinically effective. Consequently, its value in psoriasis and similar immune diseases should be further determined. Dose-finding, placebo-controlled, double-blind trials are necessary now.     

Pharmacology and Treatment Maintenance treatment of psoriasis by Tigason: a double-blind randomized clinical trial

Extensive lesions on 36 patients with psoriasis were treated by Tigason, I mg/kg/day plus PUVA until skin clearance. A clinical score was calculated for each body area, and erythema, scaling, thickness and pruritus of the lesions were scored from 0 to 3. Skin clearing was defined as a clinical score less than 10% of the initial score. Double-blind maintenance treatment was then started. This was Tigason at half of the maximal dose tolerated during the clearing phase of the treatment v. placebo. Relapse of the disease was defined as the occurrence of a clinical score greater than 50% of the initial score. Among the 36 patients randomized, 20 received placebo and 16 received Tigason. Relapses increased quickly in the patients on placebo, but occurred in few patients treated by Tigason with 60% remaining clear after 1 year (P less than 0.05). Surprisingly, the kinetics of disappearance of the most frequent side effect, cheilitis, was the same in the Tigason group and in the placebo group. This double-blind randomized clinical trial shows that Tigason at low doses is an efficient and well-tolerated maintenance treatment of psoriasis.