PASI Reduction Research Articles

PSS3 INDUCTION COST PER RESPONDER OF BRODALUMAB COMPARED WITH OTHER BIOLOGICS APPROVED FOR PATIENTS WITH MODERATE TO SEVERE PSORIASIS IN CANADA

Brodalumab is an anti-interleukin-17R antibody recently funded across several provinces in Canada for moderate-to-severe plaque psoriasis. This study estimated the cost per responder (CPR) of brodalumab at the end of induction period of therapy for adult moderate-to-severe psoriasis patients compared to currently approved biologics: adalimumab, etanercept, guselkumab, infliximab [innovator and subsequent entry biologics (SEB)], ixekizumab, secukinumab and ustekinumab. Comparative efficacy was obtained from a random effects multinomial Bayesian network meta-analysis of 43 Phase II/III clinical trials reporting Psoriasis Area Severity Index [PASI] response for biologics of interest at the end of induction period. The primary outcome was a ≥ 90 reduction in PASI (i.e., PASI 90), with PASI 75 and PASI 100 as secondary outcomes. Drug acquisition costs were sourced from the Ontario Drug Benefit Formulary and the IQVIA database DeltaPA. The CPR was calculated as the drug acquisition costs divided by the proportion of patients with PASI 90, 75, or 100, each outcome separately during the induction period. Costs were presented in Canadian dollars. The PASI 90 response was 67.2% for brodalumab and ranged from 23.7% (etanercept) to 68.2% (ixekizumab). The drug acquisition costs ranged from $5,160 (brodalumab) to $14,813 (infliximab - innovator). For PASI 90, the CPR for brodalumab was $7,679 compared with $12,346 for the infliximab-SEB, $16,967 (guselkumab), $18,502 (ixekizumab), $19,545 (ustekinumab-90), $20,710 (secukinumab), $22,136 (ustekinumab-45), $24,213 (adalimumab), $24,730 (infliximab, innovator), $41,112 (etanercept). For PASI 75 and PASI 100, the CPR for brodalumab was $5,837 and $13,797 respectively. These were followed by the infliximab SEB at $8,783 and $24,406 for PASI 75 and PASI 100. The CPR of brodalumab at the end of induction period is the lowest across the comparators for all three PASI outcomes, hence providing the best value for money for patients, prescribers and the healthcare system as a whole.

Palmoplantar psoriasis: a comparative therapeutic study

<p class="abstract"><strong>Background:</strong> Psoriasis is an immunologically mediated inflammatory dermatosis presenting with extremely variable clinical manifestations ranging from indolent lesions to life threatening forms of pustular and erythrodermic psoriasis. Palmoplantar psoriasis present as hyperkeratotic scaly plaques with fissures and can be managed with different treatment forms. This study was done to compare the efficacy between topical and systemic treatment options.</p><p class="abstract"><strong>Methods:</strong> The study was conducted in a tertiary level teaching hospital after ethical committee clearance. Fifty patients with palmoplantar psoriasis were allocated into the two groups using simple random sampling. PPPASI scoring was calculated to assess the extent of involvement. Patients in Group A were prescribed calcipotriol with clobetasol propionate ointment. Group B patients were given tablet methotrexate.<strong></strong></p><p class="abstract"><strong>Results:</strong> Twenty eight patients were males M: F of 1.27: 1. Mean age was 36. Mean duration of illness was eleven months. Most of these patients were manual laborers. 32 patients had lesions over both palms and soles, 9 over palms alone and 9 involving soles alone. Mean PASI reduction at 16 weeks was seen maximum with methotrexate. Compliance was comparatively good with methotrexate than topical. Though mean PASI reduction and compliance was good, relapse rates were higher with methotrexate in our study.</p><p class="abstract"><strong>Conclusions:</strong> There was no significant change in clinico-epidemiology and presentation of palmoplantar psoriasis. Methotrexate was observed to be the more efficacious modality in treating palmoplantar psoriasis.</p>

Comparative study of oral methotrexate and narrow band ultraviolet-B in chronic plaque psoriasis: a study from urban Karnataka

<p class="abstract"><strong>Background:</strong> Treatment of psoriasis continues to be a challenge. It is often frustrating experience for dermatologists. Methotrexate or PUVA or NBUVB when used properly, can produce good to excellent clinical benefit with minimal side effects. The objective of the study was to compare the efficacy and safety of oral methotrexate and NBUVB in the treatment of chronic plaque psoriasis.</p><p class="abstract"><strong>Methods:</strong> 100 patients of chronic plaque psoriasis attending the skin department of Navodaya Medical College and Hospital, Raichur from November 2012 to April 2014 were included in the study. Group A exhibited to Oral methotrexate and group B to NBUVB. Outcome was measured in terms of PASI 75 (it means 75% reduction in original PASI). Data was analysed using SPSS 19.0 version.<strong></strong></p><p class="abstract"><strong>Results:</strong> In Group A mean age was 33.68 years and in Group B mean age 33.7 years. The difference in mean PASI at baseline, at 4 and 8 weeks using oral methotrexate as well as NBUVB was found to be highly significant (<0.001). PASI score was less in-group using methotrexate at 4 and 8 weeks interval (<0.05). Mean time taken for PASI 75 in the baseline PASI score in Group A was 9.62±1.3 weeks whereas in Group B it was 11.3±0.7 weeks. Side effects were higher in group B (60%) compared to group A (36%).</p><p class="abstract"><strong>Conclusions:</strong> Improvement in the PASI score was best with methotrexate than NBUVB. The side effects observed in a methotrexate were minimal compared to NBUVB.</p>

Secukinumab for the treatment of residual psoriasis: a case series

Patients with plaque-type psoriasis persisting in limited and critical areas often require further treatment even after a PASI reduction has been obtained. Due to its alternative mechanism of action, secukinumab may be a therapeutic upgrade for patients who respond to anti-TNF-α drug but have persistent disease in limited and critical areas. This paper describes our experience in patients with residual psoriasis limited to critical areas, after anti-TNF-α treatment, who subsequently received secukinumab. Specifically, before secukinumab, 4 patients were treated with acitretin and 8 patients with cyclosporine followed by adalimumab or etanercept. Eleven of 12 patients achieved PASI 90/100 at week 3/5, retaining the effect for 52 weeks of treatment, with irrelevant residual scalp lesions. The non-responder patient had been treated with cyclosporine. Secukinumab improvement was independent from the previous treatment (acitretin vs cyclosporine or adalimumab vs etanercept). Secukinumab may be effective and safe for the treatment of patients with residual psoriasis that still affects the patient’s life.

Curcumin nanoparticles potentiate therapeutic effectiveness of acitrein in moderate-to-severe psoriasis patients and control serum cholesterol levels.

In this study, nanoparticles of curcumin were developed and orally administered to moderate-to-severe psoriasis (Psoriasis Area Severity Index values, PASI > 10) patients, in a placebo controlled, double blind, randomised clinical trial to evaluate the effectiveness. Diverse binary systems of curcumin and hydrophilic polymers were investigated to optimise solubility and stability in terms of curcumin residual content and size of the crystals. Nanocrystals of curcumin stabilised with PVP (1 : 0.5, w/w), were characterised using X-ray diffraction, differential scanning calorimetry, TEM analyses and stability studies. The formulation was evaluated with a parallel artificial membrane permeability assay to predict the passive intestinal absorption. The first group of patients was treated orally with acitretin (0.4 mg/kg per day) plus nanocurcumin (3 g/day), the second group with acitretin, for 12 weeks. Curcumin nanoparticles were homogeneous and stable systems. Curcumin permeability was significantly enhanced when compared with aqueous saturated solution of curcumin. The reduction in PASI was significantly higher in patients treated with curcumin (P < 0.0001) and cholesterol serum levels remained unchanged in patients treated with acitretin plus nanocurcumin. Curcumin nanoparticles represent an effective adjuvant therapy in moderate-to-severe psoriasis patients treated with oral acitretin, improving their lipid serum profile.

Biological therapy downregulates the heterodimer S100A8/A9 (calprotectin) expression in psoriatic patients.

The pathophysiology of psoriasis is very complex and involves an interplay between immune cells and keratinocytes. The keratinocyte production of calprotectin (S100A8/A9), induced by the inflammatory psoriatic milieu, may be involved in initiating immune cell invasion, as well as in propagating inflammation. However, the exact role of calprotectin in psoriasis remains unclear. Therapeutic approaches utilizing adalimumab, etanercept and ustekinumab are widely used in psoriatic treatment, but their anti-inflammatory mechanisms are not fully understood. The aim of this study was to investigate, by immunohistochemical analysis, the expression of the heterocomplex S100A8/A9 in lesional skin from psoriatic patients undergoing biological therapy with adalimumab, etanercept or ustekinumab. Our results showed that S100A8/A9, absent or present at very low level in skin biopsies from healthy subjects, is dramatically upregulated in each epidermal layer from psoriatic patients. Interestingly, calprotectin was mainly localized in keratinocyte nuclei from psoriatic patients, suggesting a role of S100A8/A9 in keratinocyte nuclear function. Furthermore, we have shown that the biological treatment induced a drastic reduction of S100A8/A9 expression in skin biopsies from treated patients, correlating with PASI reduction. Our results suggest that calprotectin may play a crucial role as a significant marker of inflammation in psoriasis, and that its reduction of expression may be considered a favourable prognostic marker in psoriasis.

IL12B, IL23A, IL23R and HLA-C*06 genetic variants in psoriasis susceptibility and response to treatment

The role of interleukin-23 is crucial in the pathogenesis of psoriasis, and IL23A, IL12B and IL23R genetic variants have been associated with the disease in genome-wide association studies. In the current paper we have conducted a confirmation study of the abovementioned genetic factors in a case-control analysis of 507 psoriatic patients and 396 controls from a Polish population, and subsequently analyzed the impact of genetic variants on response to topical and NB-UVB therapy in a subset of 306 patients. Case-control analysis revealed an association of IL12B rs3212227 and IL23R rs11209026 minor allele carrier status with reduced odds for psoriasis (OR = 0.66, 95%CI: 0.50–0.87, and OR = 0.41, 95%CI: 0.26–0.67, respectively), while HLA-C*06 allele carriers were more frequent in patients group (OR = 4.56, 95%CI: 3.41–6.10). The studied polymorphic variants of IL12B, IL23A, and IL23R genes did not influence therapy outcome, i.e. there were no significant differences in PASI reduction between patients with different genotypes. However, HLA-C*06 carriers showed poorer response to the applied treatment, when compared to non-carriers. The results of the current study confirm an association between IL12B and IL23R genetic polymorphism and psoriasis vulgaris (with a protective effect of minor alleles). HLA-C*06 carriers show reduced effectiveness of topical/NB-UVB therapy, and that observation could be potentially used in treatment personalization.

Comparison of Adalimumab and Etanercept for the Treatment of Moderate to Severe Psoriasis: An Indirect Comparison Using Individual Patient Data from Randomized Trials

ObjectivesTo compare outcomes between adalimumab and etanercept in the treatment of moderate to severe plaque psoriasis. MethodsStudy groups included patients randomized to adalimumab or placebo (REVEAL and CHAMPION trials) and those randomized to etanercept or placebo (M10-114 and M10-315 trials). Week 12 outcomes were compared between patients receiving adalimumab and those receiving etanercept after adjusting for cross-trial differences in patient characteristics using propensity score weighting and after subtracting effects of placebo. Outcomes included proportion of patients achieving 75% or more, 90% or more, and 100% reductions from baseline in the Psoriasis Area and Severity Index (PASI75, PASI90, PASI100, respectively), symptom resolution (pruritus = 0; psoriatic pain = 0), lesion resolution (minimal scores for plaque signs erythema, desquamation, and induration, and by body regions head, upper limbs, trunk, and lower limbs), absence of skin-related quality-of-life impact (Dermatology Life Quality Index [DLQI] = 0), “complete disease control” (patient’s global assessment [PtGA] = 0), and adverse events. ResultsAfter adjustment, baseline characteristics were balanced among study groups (adalimumab = 875 vs. placebo = 427; etanercept = 260 vs. placebo = 130). Compared with etanercept, adalimumab was associated with significantly better placebo-adjusted outcomes (PASI75: 62.3% vs. 42.6%; PASI90: 35.9% vs. 12.1%; PASI100: 13.1% vs. 4.9%; pruritus: 24.7% vs. 13.0%; psoriatic pain: 27.4% vs. 8.7%; DLQI: 27.7% vs. 11.7%; and PtGA: 16.4% vs. 10.6%; all P < 0.05), except for similar rates of adverse events and head-specific lesion resolution. ConclusionsCompared with etanercept, adalimumab treatment for moderate to severe plaque psoriasis was associated with greater PASI reduction, higher rates of resolution of skin signs and symptoms, and greater improvements in dermatological life quality.

Efficacy and Survival of Systemic Psoriasis Treatments: An Analysis of the Swiss Registry SDNTT

Background: The Swiss psoriasis registry SDNTT (Swiss Dermatology Network for Targeted Therapies) records the long-term safety and effectiveness of systemic treatment regimens for psoriasis. Patients and Methods: Patients with moderate to severe psoriasis are included in the SDNTT when treatment with a conventional systemic agent or biologic is initiated that was not previously used by the respective patient. Patients are followed over a 5-year period. Clinical data are obtained every 3-6 months using standardized case report forms. Here, baseline data and follow-up data for 1 year of patients included from October 2011 until December 2014 were analyzed. Results: Within 39 months, 323 patients from 7 tertiary dermatology centers in Switzerland were recruited in the SDNTT; 165 patients received biologics and 158 conventional systemic therapies. Patients treated with biologics had a significantly higher severity (PASI 11.3 vs. 9.2, BSA 15.6 vs.11.9, psoriatic arthritis 36.4 vs. 10.8%; p ≤ 0.005, p ≤ 0.013, p ≤ 0.001) and a longer duration of illness (19.2 vs. 14.4 years, p ≤ 0.003) compared to patients starting a conventional systemic treatment. PASI reduction was satisfying in both treatment groups, with 60.6% of patients treated with biologics achieving PASI75 after 1 year compared to 54.2% of patients receiving conventional systemic drugs (nonsignificant). On average, the drug survival in patients receiving a biologic therapy was significantly longer than those receiving conventional systemic treatments (30.5 vs. 19.2 months, p ≤ 0.001). Conclusions: In the real-world setting of a prospective national therapy registry, the application of current therapeutic guidelines for patients with moderate to severe psoriasis resulted in a PASI reduction of approximately 70% within the first year of treatment, but current therapeutic targets of PASI75 and PASI90 were reached in only 58 and 36% of patients, respectively, at 1 year, highlighting a gap in efficacy between selective clinical trials and the real-world setting.

Phototherapy with Narrow-Band UVB in Adult Guttate Psoriasis: Results and Patient Assessment

Background: Acute guttate psoriasis (AGP) is a distinctive clinical entity with good response to treatment with narrow-band ultraviolet B (NB-UVB). Objective: To investigate the results of NB-UVB phototherapy in adult patients with adult guttate psoriasis. Material and Methods: We carried out a prospective, open, and observational study. Patients over 18 years with more than 5% of body surface area affected were included. The PASI was assessed prior to and after treatment. The follow-up period was 18 months. After treatment, patients completed a simple questionnaire to assess their overall impression of the treatment. Results: The 67 adult patients with AGP included in this study had an initial PASI of 8.55 (SD 5.03). Patients were treated with a mean of 19.9 sessions (SD 13.5) and mean doses of 14 mJ/cm² (SD 10.5). Of the 67 patients, 52 achieved PASI90 with 96.15% of PASI reduction, and of these, 46 (88%) maintained PASI90 during the 18 months of follow-up. Patients were very satisfied with the treatment. Discussion: AGP is a defined clinical entity with a variable course. Phototherapy with NB-UVB appears to be a very good option for treatment of AGP because of the good results obtained and patient satisfaction.

Combination Therapy of Etanercept and Fumarates versus Etanercept Monotherapy in Psoriasis: A Randomized Exploratory Study

Background: Biologics are a safe and efficacious therapy for psoriasis. The drug survival of biologics may be disappointing, primarily due to loss of efficacy. Therefore, safe combination treatments are sought to improve their clinical response. Objective: To assess the efficacy, safety and tolerability of the combination therapy of etanercept with fumarates versus etanercept monotherapy. Methods: Thirty-three patients with psoriasis were randomized 1:1 to receive etanercept combined with fumarates or etanercept monotherapy. The primary outcome measure was the difference in PASI-75 response after 24 weeks; additionally, a longitudinal analysis was performed. An important secondary outcome measure was the proportion of patients with a Physician Global Assessment (PGA) of clear or almost clear. Adverse events were collected throughout the study. Results: In the combination therapy group, 78% (14 out of 18 patients) reached PASI-75 at week 24 versus 57% (8 out of 14 patients) in the monotherapy group (p = 0.27). The longitudinal analysis showed a PASI reduction of 5.97% per week for the combination therapy group and of 4.76% for the monotherapy group (p = 0.11). In the combination therapy group, 94% (17 out of 18 patients) of patients had a PGA of clear/almost clear versus 64% (9 out of 14 patients) in the monotherapy group (p = 0.064). The incidence of mild gastrointestinal complaints was higher in the combination group than in the monotherapy group. Conclusion: Using the PGA, combination therapy showed a trend towards faster improvement in the first 24 weeks. The difference in the PASI score between the two groups was not statistically significant. Addition of fumarates to etanercept for 48 weeks appeared safe with an acceptable tolerability.

Efficacy and safety of infliximab in psoriatic patients over the age of 65

ABSTRACTBackground: Clinical data on the long-term safety and efficacy of infliximab on psoriatic patients who are older than 65 years are limited.Objectives: The aim is to report the long-term efficacy, safety and tolerance of infliximab in geriatric patients.Methods: This was a retrospective study conducted at the Department of Dermatology of the University of Rome Tor Vergata. Clinical data were reported at week 12, 52, 104, 208.Results: 151 charts were evaluated. A total of 27 patients were included. Range of the age was between 65 and 85 years; mean age was 73 years ±5.4; female to male ratio was 1:2; mean age of onset of psoriasis was 43 years±17. The average of treatment duration was 39 months ±27 (range 1–100). Fourteen patients suffered from plaque type psoriasis and 13 from psoriatic arthritis. At the baseline the mean PASI score was 15.6 ± 10.2. At week 12, 52, 104, and 208 the mean PASI was 2, 2.3, 1.9 and 1.8 respectively. A reduction in the mean PASI was maintained in the long-term treatment in 12 patients (p < 0.001).Conclusion: Our data suggest that long-term treatment with infliximab is effective and safe in patients over 65 years old and that IV therapy is also associated with a high compliance.

English

Psoriasis is a chronic inflammatory disease with frequent relapses and remissions. The introduction of biologicas increased the remission periods, decreases relapse and hence improve the quality of life. Method: The study includes 17 adult patients of chronic plaque psoriasis, who received etanercept subcutaneously at a dosage of 50 mg once weekly for 24 weeks, followed by 6 months follow up. Results: At the end of 12 weeks 8 patients (47.05%) achieved more than 75% reduction of PASI and at the end of 24 weeks 9 patients(52.94%) achieved more than 75% reduction of PASI. Conclusion: Our study shows that etanercept has good efficacy without any significant side effects and it should be considered in patients with moderate to severe chronic plaque psoriasis not responding to other conventional modes of therapy. INTRODUCTION Psoriasis is a chronic inflammatory skin condition affecting approximately 2 % of the general population. Even though it has several clinical variants, chronic plaque type is the commonest that presents with silvery white scales on an erythematous base. Some patients may have associated joint involvement. The pathogenesis of psoriasis is complex it includes both innate and adaptive immune systems. Cytokines Th1 and Th17 cells have been incriminated in the pathogenesis of psoriasis. These cytokines secrete TNFα and IFN – α that leads to vasodilatation ,leukocyte migration and keratinocyte activation. This leads to activation of dendritic cells that creates a repeated cycle of inflammation. Biologics are the agents that targets genetic or immune mediator of pathophysiological process.. Among the biologics Infliximab, Etanercept, and Adalimumab targets TNF-α. Eternacept is a human fusion protein of the TNF receptor to Fc portion of IgG which binds to TNF –α to neutralize its effects. Various international studies have showed eternacept has good efficacy in chronic plaque type of psoriasis. With this background we conducted a study on efficacy of eternacept in chronic plaque psoriasis. *Corresponding author: Email: ramasamypp@yahoo.com http://dx.doi.org/10.20530/IJTA_31_18-21 ISSN 2320-138X © 2016 Table 1: Baseline PASI Score NO: AGE/SEX BASELINE PASI

Combination therapy of methotrexate plus NBUVB phototherapy is more effective than methotrexate monotherapy in the treatment of chronic plaque psoriasis

Background: The efficacy of methotrexate (MTX) plus narrowband ultraviolet B (NBUVB) phototherapy in treatment of chronic plaque psoriasis has been rarely assessed. Objectives: The objective of this study is to compare the efficacy of MTX/NBUVB phototherapy versus MTX monotherapy in treatment of chronic plaque psoriasis. Methods: Forty patients with psoriasis were enrolled into the study and classified into group A receiving oral MTX and group B receiving oral MTX plus NBUVB. Onset of improvement was ≤70% of baseline PASI. End point clearance was 90 % reduction in PASI or up to 6 months. Side effects were reported. Follow up for 12 weeks for assessment of relapse was done. Results: Of 40 patients, 35 completed the study. A higher clearance rate was achieved in patients of group B versus group A (100% versus 83%). A significant difference was reported regarding the onset of improvement and the duration required for clearance (p < 0.001) in favor of the MTX/NBUVB group. Patients in group B had a highly significant lower cumulative dose of MTX than the monotherapy group (p < 0.05). No significant difference as regard side effects and relapse was reported. Conclusion: MTX remains the mainstay in the treatment of psoriasis in developing countries and its combination with NBUVB offers a cheap and a beneficial therapeutic option.

Reduction in tissue plasmin: a new mechanism of action of narrowband ultraviolet B in psoriasis.

Plasmin (PL) is a potent inflammatory cell activator, and ultraviolet (UV)B has immunomodulatory effects on cutaneous inflammatory responses. There are no previous studies comparing the effect of narrowband (NB)-UVB on tissue PL levels in psoriasis. To estimate the possible role of PL in the pathogenesis of psoriasis, and to evaluate the effect of NB-UVB on tissue PL in psoriasis. This case-control study enrolled 21 patients with psoriasis and 20 clinically healthy volunteers matched for age and sex. Patients underwent 24 sessions of NB-UVB radiation. Biopsy samples using a 4 mm punch were taken from all patients before and after treatment and from the controls for estimation of tissue PL level by ELISA. Tissue PL was significantly upregulated in psoriasis before treatment (mean ± SD 1.73 ± 1.23 ng/mg protein) compared with controls (0.21 ± 0.15 ng/mg protein) (P < 0.001). A statistically significant positive correlation (P = 0.02) was found between the tissue PL before treatment and the Psoriasis Area and Severity Index. Patients received 24 sessions of NB-UVB, with a mean cumulative dose of 23.25 ± 8.14 mJ/cm(2) . Tissue PL levels were reduced by a mean of 30.3% post-treatment compared with baseline (P < 0.001). The reduction in Pl levels was significantly correlated with the cumulative dose of NB-UVB, and with the percentage reduction in PASI (P < 0.001). Our study highlights the possible role played by tissue PL level in the pathogenesis of psoriasis. PL level appears to reflect disease severity, and is a possible marker of therapeutic efficacy of NB-UVB on psoriatic skin.

Anti-TNFα therapy in the management of psoriasis: experience of a state referral center.

BACKGROUNDPsoriasis is a chronic immune-mediated disease, characterized by increased levels of TNFα. Anti-TNFα agents have revolutionized the treatment of severe psoriasis by targeting an important molecule involved in its pathogenesis.OBJECTIVESWe report the experience of a state referral center that uses anti-TNFα agents for psoriasis.METHODSWe conducted a retrospective case series. Seventy-four out of 120 patients met the inclusion criteria. Clinical and laboratory data was analyzed using the chi-squared, Wicoxon and McNemar's tests. Associations were considered statistically significant when p-value<0.05.RESULTSForty-one subjects (55.40%) were male, with a mean age of 47.69±14.99 years. Median disease duration and pre-treatment PASI were 14.0 months (IQR 9.0-20.0), and 13.55 points (IQR 8.5-20.32). Sixty patients (81.10%) had arthropathic psoriasis. Forty-six subjects (62.20%) had comorbidities; the most frequent was dyslipidemia (25.70%). In 55.40% of patients, insufficient response to conventional therapies was the principal indication for using anti-TNFα drugs. Clinical improvement occurred in 93.20% of cases, and the post-treatment PASI median was 0.0 points (IQR 0.0-0.0). Adverse effects occurred in 6.80% of patients. Infections and elevation of transaminases occurred in 28.40% and 8.10% of cases, respectively.CONCLUSIONPost-treatment reduction in PASI was satisfactory and the occurrence of adverse effects was minor, mostly mild infusion effects and local reactions at drug administration sites.

Genetic markers of treatment response to tumour necrosis factor-α inhibitors in the treatment of psoriasis.

Anti-tumour necrosis factor (TNF)-α therapies have revolutionized the treatment of psoriasis; however, up to 50% of patients do not respond satisfactorily. Identification of pharmacogenetic markers of treatment response is an important stop in the development of individually tailored treatment. The objective of this study was to assess the association of human leucocyte antigen (HLA)-C, killer immunoglobulin receptor (KIR) and vitamin D receptor (VDR) genotypes with response to treatment by etanercept and adalimumab. This was a study of 138 patients with severe chronic plaque psoriasis who were treated with etanercept and/or adalimumab. Patients were classified as responders if they achieved a 75% reduction in PASI (PASI75) or were almost clear of psoriasis after 24weeks of therapy. The frequencies of HLA-C and KIR haplotypes and VDR polymorphisms were compared in responders and nonresponders. The frequency of all HLA-C and KIR genotypes were compared between the 138 patients with psoriasis and 247 healthy donors. The number of patients classified as responders was 46 of 94 (49%) in the etanercept group and 50 of 76 (66%) in the adalimumab group. None of the HLA-C, KIR or VDR genotypes examined was predictive of treatment response. Compared with healthy controls, patients with psoriasis were more likely to have the HLA-C*06 genotype (P<0.001) and less likely to have the HLA-C*07 genotype (P<0.001), whereas there was no significant difference in frequencies of any KIR subtype. Using the candidate gene approach to identify biomarkers of treatment response in psoriasis may have limited utility. This was a small study with limited power. Future larger studies are needed to further examine these findings and to explore alternative approaches to identify predictors of treatment response to biological agents.

Evaluation of therapeutic response of methotrexate and calcipotriol combination compared with methotrexate alone in plaque psoriasis

Introduction: Psoriasis is a common chronic, non-contagious, immune mediated disease. Plaque psoriasis is characterized by thick, white, silvery or red patches on the skin. Plaque psoriasis mainly affects scalp, and palms of hands and soles of feet. T-cells are a type of immune system cells which protect the body from foreign substances. But during psoriasis T-cells activated at a great rate than normal, in turn release of cytokines increases as a result skin cells growing too quickly, moving to the surface to the skin and appear on the skin as dead cells. Materials and Methods: Plaque psoriasis is common form of psoriasis, which mainly affects palms of hands and soles of feet and scalp. Out of 76 patients with plaque psoriasis we selected 50 patients based on PASI scores. Within the 50 patients, 32 patients with Palmoplantar psoriasis and 18 patients with scalp psoriasis. All 50 patients were subjected to randomized control trail, so each type of psoriasis is divided into two groups i.e. A and B. All A group patients were treated with MTX, whereas all B group patients were treated with combination of MTX and Calcipotriol. All necessary investigations like complete blood count, liver enzyme,creatinine, urea, alkaline phosphate, PASI were measured at 0, 2,4 6,8 weeks interval. Results: We observed that, a significant reduction in PASI is observed with combination of MTX and Calcipotriol as compared to Methotrexate alone. Conclusion: From the above study we concluded that, combination of MTX and Calcipotriolis more effective than MTX alone in plaque psoriasis.

Responsiveness to Change and Interpretability of the Simplified Psoriasis Index

The Simplified Psoriasis Index (SPI) is a summary measure of psoriasis with separate components for current severity (weighted for functionally or psychosocially important sites), psychosocial impact, and past behavior. The current severity components of the professionally assessed SPI (proSPI-s) and self-assessed SPI (saSPI-s) have each been shown to be valid and reliable. Their responsiveness to change and equivalence to the current standard (Psoriasis Area and Severity Index, PASI) were investigated. Responsiveness and minimum clinically important differences (MCIDs) were derived from PASI changes from baseline at weeks 4 (n=100) and 10 (n=65) in patients commencing therapy for psoriasis. Receiver operating characteristic (ROC) analysis confirmed that both measures detected responsiveness well (area under the curve (AUC)=0.72-0.96). On ROC and PASI-based anchor analysis, MCIDs equated to mean absolute and percentage changes of 5 and 60% (proSPI-s), and 7 and 70% (saSPI-s). Satisfactory response as defined by 75% reduction in PASI equated to 85 and 95% reductions in proSPI-s and saSPI-s, respectively. PASI-equivalent cutoff scores for mild (PASI<10) and severe (PASI>20) psoriasis were <9 and >18 for proSPI-s (n=300) and <10 and >20 for saSPI-s (n=200; AUC=0.86-0.96). These studies further support the validity of SPI for use in routine clinical practice.

Long-term response to etanercept monotherapy in moderate to severe psoriasis: assessment in daily practice by the maintenance of low values of PASI and BSA

Introduction:Efficacy and safety profiles of etanercept have been proved in numerous clinical trials; however, efficacy is determined by means of PASI 75 and few studies consider the maintenance of long-term response. The aims of this study were to provide data on long-term response to etanercept monotherapy in daily practice and to propose a method to assess the efficacy based on the maintenance of low PASI and BSA. Methods:Patients with moderate–severe psoriasis treated with etanercept 50 mg weekly, achieving at least PASI 50 at 12 weeks, were included. Response was expressed as the percentage of patients maintaining PASI and BSA ≤5 and ≤3, respectively. Results:We included 76 patients (73.7% male and 26.3% female). PASI remained ≤5 in 71.1%, 61.3%, 54.4%, 38.3%, 8.6% and 5.9% of patients and ≤3 in 51.3%, 46.8%, 42.1%, 34%, 8.6% and 5.9% at 3, 12, 18, 24, 36 and 42 months. Conclusions:The maximum response is achieved between 6 and 9 months and remains stable in about 50% of cases until 18–24 months. Response maintains beyond 42 months in 6%. Maintenance of low PASI and BSA may be a most useful measure than the initial PASI reduction, which not always means enough improvement for the patient.