Chronic hand eczema - self-management and prognosis: a study protocol for a randomised clinical trial

Background

The purpose of this study was to estimate the annual and per-patient budget impact of the treatment of moderate to severe psoriasis in Greece before and after the introduction of ustekinumab.

Methods

A budget impact model was constructed from a national health system perspective to depict the clinical and economic aspects of psoriasis treatment over 5?years. The model included drug acquisition, monitoring, and administration costs for both the induction and maintenance years for patients in a treatment mix with etanercept, adalimumab, infliximab, with or without ustekinumab. It also considered the resource utilization for non-responders. Greek treatment patterns and resource utilization data were derived from 110 interviews with dermatologists conducted in February 2009 and evaluated by an expert panel of 18 key opinion leaders. Officially published sources were used to derive the unit costs. Costs of adverse events and indirect costs were excluded from the analysis. Treatment response was defined as the probability of achieving a PASI 50, PASI 75, or PASI 90 response, based on published clinical trial data.

Results

The inclusion of ustekinumab in the biological treatment mix for moderate to severe psoriasis is predicted to lead to total per-patient savings of ?443 and ?900 in years 1 and 5 of its introduction, respectively. The cost savings were attributed to reduced administration costs, reduced hospitalizations for non-responders, and improved efficacy. These results were mainly driven by the low number of administrations required with ustekinumab over a 5?year treatment period (22 for ustekinumab, compared with 272 for etanercept, 131 for adalimumab, and 36 for infliximab).

Conclusions

The inclusion of ustekinumab in the treatment of moderate to severe psoriasis in Greece is anticipated to have short- and long-term health and economic benefits, both on an annual and per-patient basis.     

Evaluación de la eficiencia de los tratamientos biológicos en la psoriasis moderada a grave en España: análisis de coste por número necesario a tratar (NNT)

Background and objectivesPsoriasis is a chronic inflammatory skin disease with an estimated prevalence in Spain of 2.3% of the population. Approximately 30% of patients have moderate-to-severe forms. Treatment with biologic agents is proving to be a step forward in the management of the disease, although these treatments are very expensive. The objective of this study was to determine the efficiency, in terms of cost per number needed to treat (NNT), of the biologic drugs available in Spain for the treatment of moderate to severe plaque psoriasis.MethodsNNT data were obtained from a network meta-analysis that included all randomized clinical trials of biologic drugs sold in Spain. The cost of each treatment was calculated based on the approved dosage for the first year of treatment, as indicated in the Summary of Product Characteristics. These data were used to calculate the cost per NNT of the drugs for various PASI scores (75, 90, and 100). A sensitivity analysis was performed taking into consideration only the PASI-response measurement time (after 10, 12, or 16 weeks, depending on the drug).ResultsThe order of efficiency, from most to least efficient, in the case of a PASI 75 response was ixekizumab > ustekinumab 45 mg > ustekinumab 90 mg > secukinumab > infliximab > etanercept > adalimumab. The order for PASI 90 was ixekizumab >secukinumab >ustekinumab 45 mg > ustekinumab 90 mg > infliximab > adalimumab > etanercept. The order for PASI 100 was ixekizumab > secukinumab > infliximab > ustekinumab 90 mg > ustekinumab 45 mg > adalimumab > etanercept. The sensitivity analysis showed some changes in the order, depending on the response-assessment period.ConclusionsThe findings show a link between the efficacy of the biologic therapies available in Spain for the treatment of moderate-to-severe plaque psoriasis and their efficiency. Ixekizumab had the lowest cost per NNT for all PASI-response scores (75, 90, and 100) during the first year of treatment.     

Cost-efficacy of adalimumab, etanercept, infliximab and ustekinumab for moderate-to-severe plaque psoriasis

Background Different biological agents are used for the treatment of psoriasis. Previous data have shown adalimumab to be the most efficient drug in terms of cost‐efficacy. However, newer data are required to include recent drugs. Objective To estimate the cost‐efficacy ratios of biological agents licensed in Spain (adalimumab, etanercept, infliximab and ustekinumab) for the treatment of patients with moderate‐to‐severe psoriasis. Methods An economic evaluation model was developed by building a decision tree for each drug regimen for which scientific evidence was available. The payer perspective (Spanish National Health System) was considered, taking into account only the drug costs. Data on efficacy [proportion of patients with a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75)] reported in the randomized controlled trials were used. When more than one trial for each treatment had been published, a meta‐analysis was performed. In case of weight‐dependent doses (infliximab), weight of the study subjects was standardized by age and gender of the Spanish population, corrected for the increase in weight in subjects with psoriasis. Uncertainty was assessed by sensitivity analysis. Results Incremental efficacy ranged from 31.19% (etanercept at a dosage of 25 mg twice a week for 12 weeks) to 78.35% (infliximab at 5 mg/kg for 24 weeks). Efficiency, in terms of incremental cost‐efficacy, ranged from 8013€ (adalimumab) to 17 981€ (ustekinumab at a dose of 90 mg) per PASI 75 responder gained. Conclusion In terms of cost‐efficacy, the most efficient biological drug was adalimumab. The robustness of this finding was confirmed by sensitivity analysis.     

Biological therapies for psoriasis: Adherence and outcome analysis from a clinical perspective

We evaluated and compared patients' long‐term adherence to biological therapies in a real‐life clinical setting. Secondary aims included weight changes on biological therapy and reporting adverse effects. This prospective case‐note review included 58 patients, undergoing 84 treatment series including etanercept (21), adalimumab (24), infliximab (14) and ustekinumab (25). Patients' adherence was greatest with ustekinumab (being 6.7‐fold less likely to withdraw from treatment than etanercept, P = 0.014), while the difference in treatment adherence of adalimumab and infliximab compared to etanercept was not statistically significant. Adalimumab and infliximab were associated with an increase in weight, while ustekinumab was associated with weight loss compared with etanercept (not statistically significant). Long‐term patient adherence to biologic therapy in patients with psoriasis is greatest with ustekinumab.     

Safety and effectiveness of ustekinumab and antitumour necrosis factor therapy in patients with psoriasis and chronic viral hepatitis B or C: a retrospective,multicentre study in a clinical setting

Background Both the safety and efficacy of biologic therapy may be affected in the presence of highly prevalent chronic viral hepatitis. Objectives To evaluate the safety and effectiveness of ustekinumab and antitumour necrosis factor therapy in patients with psoriasis and concomitant chronic viral hepatitis. Methods This was a retrospective, multicentre study. Twenty‐five patients with psoriasis and concurrent hepatitis C virus (HCV) (20 patients) or hepatitis B virus (HBV) (five patients) infection who had received at least one biologic agent (etanercept, 21 treatments; adalimumab, four; ustekinumab, four; infliximab, two) were included. Clinical, imaging and laboratory data were recorded. Results In the case of HCV infection, the majority of the patients did not exhibit increases in their viral load or serum liver tests. Aspartate aminotransferase, alanine aminotransferase and gamma glutamyl transpeptidase were doubled from the baseline measurement in only one patient treated with etanercept. Two other cases exhibited viral load increases during the follow‐up period. In total, 18 of the 26 treatments achieved a 75% improvement in their Psoriasis Area and Severity Index (PASI 75) score during the follow‐up period. Two patients treated with etanercept were diagnosed with hepatocellular carcinoma. In the case of HBV infection, all of the patients were being treated with antiviral therapy, and none presented significant variations in viral load or serum liver enzymes. All patients achieved a PASI 75 during follow‐up. Conclusions Biologic therapy was effective and safe for the majority of our patients with HCV and HBV infection, although there may be a risk of reactivation or aggravation. We describe the first cases to receive ustekinumab. The use of biologics should be limited to those cases in which the risk–benefit ratio is justified.     

Successful adalimumab treatment of a psoriasis vulgaris patient with hemodialysis for renal failure: A case report and a review of the previous reports on biologic treatments for psoriasis patients with hemodialysis for renal failure

The efficacy and safety of biologic treatments have been established in patients with moderate to severe psoriasis, but there are few reports on biologic therapy for patients with psoriasis complicated by end‐stage renal failure on hemodialysis (HD). In this report, we demonstrated the efficacy and safety of adalimumab for patients with severe psoriasis on HD. A 46‐year‐old Japanese man with a 14‐year history of psoriasis was referred to our clinic in September 2009. He had developed hypertension and renal failure during a 7‐year history of cyclosporin treatment. With the infliximab treatment, he achieved 75% improvement of the Psoriasis Area and Severity Index (PASI) score within 3 months from the PASI of 42.3 before the treatment. However, his renal failure gradually deteriorated, and HD was initiated at 1 year after the introduction of infliximab. Because of hydration during the i.v. injection of infliximab, he developed pulmonary edema with every infliximab treatment after starting HD. We switched to ustekinumab treatment, but his psoriasis was not improved. Then, we switched to adalimumab and achieved a PASI‐100 response within 2 months. The patient received adalimumab treatment for more than a year without any adverse effects. In addition to our case, five articles reported cases of psoriasis patients with renal failure on HD who were treated with biologics. The psoriatic lesions were improved by biologics in these cases, and no severe adverse effects on the renal function were reported. Thus, biologics are a reasonable treatment option for patients with severe psoriasis with renal failure on HD.     

Responses to ustekinumab in the anti‐TNF agent‐naïve vs. anti‐TNF agent‐exposed patients with psoriasis vulgaris

Background Approximately 20–30% of patients with psoriasis treated with anti‐tumour necrosis factor α (TNFα) agents will discontinue treatment within 2 years due to loss of efficacy or side‐effects. Switching to another anti‐TNFα agent produces clinical responses inferior to previously untreated patients. Ustekinumab binds to the p40 subunit of interleukin (IL)‐12 and IL‐23 and provides a mechanism of action independent of TNFα. Objective To investigate the efficacy of ustekinumab in a clinical practice setting and to compare treatment responses to ustekinumab in patients previously treated with TNFα inhibitors and anti‐TNFα‐naïve patients. Methods Patients receiving either ustekinumab (n = 71) or the subcutaneous TNFα inhibitors adalimumab or etanercept (n = 108) were identified through the registry of psoriasis patients in our Institutions. Efficacy effect outcome was a 75% improvement in the psoriasis area severity index (PASI75). Kaplan–Meier statistics evaluated the adherence to the treatments expressed as drug survival rate. Results PASI75 was achieved in 80% of the ustekinumab‐treated patients after a median time of 112 days. There was no difference in efficacy in anti‐TNFα‐naïve patients compared with anti‐TNFα unresponsive patients. Patients treated with ustekinumab showed a superior adherence to treatment in comparison with adalimumab and etanercept. Limitations Patients were non‐randomly assigned to treatment, which potentially may lead to biases. Observation time was short (1 year). Conclusion In clinical practice, the short‐term efficacy and patient adherence to ustekinumab are excellent and comparable to the data obtained in clinical trials. Lack of response to previous anti‐TNF treatment does not impair clinical response to ustekinumab.     

Use of biological drugs in patients with psoriasis and psoriatic arthritis in Italy: Results from the PSONG survey

This Italian multicenter retrospective study compared the drug survival and efficacy of different anti‐TNF agents in psoriasis (PsO) and psoriatic arthritis (PsA) patients. A database of PsO/PsA patients treated with adalimumab, etanercept, and infliximab from May 2013 to May 2014 was analyzed. PASI 75, 90, and 100 was calculated at each time point to evaluate efficacy. Drug survival rate and probability of maintaining PASI response were evaluated. The impact of dependent variables on probability of PASI 75 loss was evaluated by logistic regression. 1,235 patients were included, 577 with PsO and 658 with PsA. Highest survival rates were observed with adalimumab followed by etanercept and infliximab in PsO and PsA patients. The probability of maintaining PASI response was significantly higher for adalimumab followed by infliximab. For PsO patients, the odds of losing PASI 75 was higher in etanercept‐treated patients (OR: 8.1; 95% CI: 4.2–15.6, p < .001) or infliximab (OR: 6.6; 95% CI: 2.6–16.3, p < .001) vs. adalimumab. Likewise, for PsA patients the odds of losing PASI 75 was higher in etanercept‐treated patients (OR: 2.3; 95% CI: 1.4–3.8, p = .01) or infliximab (OR: 2.2; 95% CI: 1.1–4.1, p = .018) vs. adalimumab. Adalimumab could be the best therapeutic option over other anti‐TNF agents for the treatment of PsO and PsA patients.     

Switching from etanercept to adalimumab is effective and safe: results in 30 patients with psoriasis with primary failure,secondary failure or intolerance to etanercept

Background Knowledge on the sequential treatment of psoriasis with biologics with regard to efficacy and safety is sparse. This also applies to the efficacy and safety of adalimumab in patients previously treated with etanercept. The relationship between the reasons for discontinuation of etanercept and the response to adalimumab is not clear in psoriasis. Objectives To evaluate the efficacy and safety of adalimumab in patients with psoriasis with primary failure, secondary failure or intolerance to etanercept in daily practice. Methods Data were extracted from two prospective registries from all patients with psoriasis with failure on etanercept treatment, who switched to adalimumab therapy. Thirty patients fulfilled these criteria. All patients were naive to biologics when etanercept was initiated. Primary endpoints were the percentage of patients achieving a 50% or 75% improvement of the baseline Psoriasis Area and Severity Index (PASI) score (PASI 50 and PASI 75, respectively) at weeks 12, 24 and 48. Secondary endpoints were the percentage of patients achieving PASI 90, the mean percentage improvement in the PASI score from baseline and the adverse event rate. Results Compared with the baseline PASI score before the start of etanercept, the mean percentage improvement in PASI and the PASI 50/75/90 response rates to adalimumab until week 48 were comparable to those achieved with etanercept. In the patients failing on etanercept, PASI 75 was achieved by 27%, 36% and 54% at weeks 12, 24 and 48 of adalimumab treatment, respectively. The majority of patients showed a beneficial response to adalimumab, irrespective of the reason for discontinuation of etanercept. Previous treatment with etanercept did not increase the adverse event rate nor change the nature of the side‐effects. Conclusions Adalimumab seems to be an effective and safe treatment option for patients with psoriasis who failed on etanercept treatment irrespective of the reason for discontinuation.     

Adalimumab for psoriasis patients who are non-responders to etanercept: open-label prospective evaluation

Background  Targeted biologic therapies have made a significant impact on the treatment for moderate to severe psoriasis. In the United Kingdom, the National Institute for Health and Clinical Excellence recommends etanercept, a human recombinant tumour necrosis factor (TNF) receptor fusion protein, for moderate to severe psoriasis patients who have failed conventional therapies. There is, however, no data available on the role of other TNF antagonists for patients who have failed etanercept. Adalimumab, a fully human, anti-TNF monoclonal antibody, is approved for treatment of moderate to severe psoriasis.
Objectives  To assess the efficacy and safety of adalimumab (40 mg weekly) in psoriasis patients who were non-responders to high-dosage etanercept (50 mg twice weekly).
Methods  All patients attending a tertiary referral service for severe psoriasis who were non-responders to high-dosage etanercept [i.e. failed to achieve ≥ 50% improvement in Psoriasis Area and Severity Index (PASI 50) after 12 weeks of treatment] were considered for open-label adalimumab therapy for 12 weeks. Details on clinical course, PASI, Dermatology Life Quality Index (DLQI) and adverse events were recorded at baseline and weeks 2, 4, 8, and 12.
Results  Four of five patients in this study had reached at least PASI 50 by week 12. Of these, two patients achieved a 75% improvement in PASI (PASI 75). No serious adverse events were reported.
Conclusions  Initial data from this open-label prospective evaluation suggests that weekly adalimumab therapy is an effective treatment for patients with severe psoriasis who had failed to respond to at least 3 months of high-dosage etanercept.     

Antidrug antibodies in psoriasis: a systematic review

Antidrug antibodies (ADAs) against biological agents may be clinically significant and potentially alter a biological drug's treatment efficacy. This systematic review aims to (i) determine the prevalence of ADAs against infliximab, etanercept, adalimumab and ustekinumab in patients with psoriasis; (ii) ascertain whether ADAs are associated with changes in drug efficacy; and (iii) explore the use of concomitant methotrexate to prevent ADA formation. Through a systematic search using Medline and Embase from 29 January 1950 to 29 March 2013, we identified 25 studies that met the inclusion criteria. Of 7969 patients with psoriasis, 950 tested positive for ADAs. Antibodies against infliximab, etanercept, adalimumab and ustekinumab were reported in 5·4–43·6%, 0–18·3%, 6–45% and 3·8–6% of patients, respectively. Anti‐infliximab antibodies were associated with lower serum infliximab concentrations in three studies, and decreased treatment response in five studies. ADAs against etanercept were non‐neutralizing and not associated with any apparent effects on clinical response. Antiadalimumab antibodies were associated with lower serum adalimumab concentrations in three of five studies, and reduced clinical efficacy in four studies. Two of six studies reported that antiustekinumab antibodies were associated with lower Psoriasis Area and Severity Index responses, and three ustekinumab studies noted that most of these antibodies were neutralizing. Although the use of concomitant methotrexate with biological agents to prevent ADA formation in other immune‐mediated diseases is promising, their use in psoriasis is sparse. ADA development remains a challenge with biological therapies and therefore should be considered in patients with psoriasis who experience diminished treatment response.     

Efficacy of biologics in the treatment of moderate to severe psoriasis: a network meta-analysis of randomized controlled trials

Background Ustekinumab, a novel monoclonal antibody for the treatment of moderate to severe plaque‐type psoriasis, has recently received regulatory approval in Europe, bringing the total number of biologic agents licensed in this indication to five. To assist treatment selection in daily practice it is essential to understand the benefit/risk profile of these agents and in the absence of a clinical trial comparing all available biologics a number of reviews have used statistical techniques to generate estimates of the comparative effectiveness of these therapies through the available network of randomized clinical trials. These estimates have previously been published for a limited range of psoriasis biologic treatments, although, to date no review has compared all the currently available agents in Europe. Objectives To estimate the comparative effectiveness of all biologic agents indicated in the treatment of moderate to severe psoriasis currently available in Europe based on the primary trial endpoints. Methods A number of databases were searched for details of randomized controlled trials of available biologics in the treatment of plaque‐type psoriasis in adults. Comparative effectiveness was estimated based on the reported Psoriasis Area and Severity Index (PASI) 50, 75 and 90 response rates. A network meta‐analysis conducted on the ordered probit scale and implemented as a Bayesian hierarchical model provided estimates for the probability of response and relative risk vs. placebo, based on all observed comparisons. Results Twenty trials were included in the meta‐analysis including patients with a mean disease duration of 18–22 years. Based on the indirect comparison and given a placebo PASI 50 response of 13%, infliximab had the highest predicted mean probability of response at PASI levels 50 (93%), 75 (80%) and 90 (54%), followed by ustekinumab 90 mg at 90%, 74% and 46%, respectively, and then ustekinumab 45 mg, adalimumab, etanercept and efalizumab. Conclusions The ordered probit model allowed a quantitative comparison of all currently licensed biologics, providing estimates on comparative effectiveness and a suggested ranking of treatments that is of potential use to decision‐makers. However, the analysis is based on indirect comparisons of the primary endpoint reported from short‐term randomized trials.     

Ustekinumab does not increase body mass index in patients with chronic plaque psoriasis: a prospective cohort study

Background Chronic plaque psoriasis is frequently associated with metabolic disorders including obesity. Antitumour necrosis factor α treatments can induce body‐weight increase in patients with psoriasis. Information on the effect of ustekinumab on body weight is not available. Objectives To investigate whether therapy with ustekinumab is associated with changes in body mass index (BMI) in patients with chronic plaque psoriasis. Methods A prospective, multicentre study comparing the changes in BMI in two closed cohorts of patients with psoriasis during 7‐month treatment with ustekinumab (n = 79) or infliximab (n = 83). Results Patients treated for 7 months with infliximab showed a significant (P < 0·001) increase in mean BMI (2·1 ± 4·5%) and body weight (2·5 ± 3·3 kg) compared with patients treated with ustekinumab (0·1 ± 3·3%; 0·6 ± 1·1 kg). Some 45% of patients treated with infliximab had a BMI increase > 2%, compared with only 11% of those receiving ustekinumab (P = 0·01). In the multivariate analysis, all other clinical parameters predicted the BMI increase, except for the use of infliximab. At month 7, 96% of patients treated with infliximab and 82% of patients treated with ustekinumab achieved at least a 50% improvement from their baseline psoriasis area and severity index (PASI 50), and 69% of the infliximab group compared with 58% of the ustekinumab group achieved at least PASI 75. There was no difference in the proportion of PASI 50 and PASI 75 responders between the two groups. Conclusions In contrast to infliximab, ustekinumab does not increase BMI in patients with chronic plaque psoriasis. This difference could be taken into account in the selection of biologics when treating patients with psoriasis.     

Drug survival rates in patients with psoriasis after treatment with biologics

Clinically, patients' adherence to biologic treatment is not only related to efficacy but also to adverse events, cost and other factors. To evaluate long‐term viability of biologic treatment, both the percentage of and reasons for discontinuation of treatment were investigated. In this study, patients treated with infliximab (n = 38), adalimumab (n = 59) and ustekinumab (n = 30) were included and observed for 12 months. Clinical efficacy was evaluated using a 75% reduction of Psoriasis Area and Severity Index score (PASI‐75), and patients who discontinued treatment were considered as not having achieved PASI‐75. In addition, drug survival rate (DSR) was investigated. In patients treated with infliximab, PASI‐75 was 68.4% and DSR was 73.3% by the end of treatment. In patients treated with adalimumab, PASI‐75 was 50.8% and DSR was 79.7%. In patients treated with ustekinumab, PASI‐75 was 63.3% and DSR was 96.7%. Several patients discontinued treatment because of insufficient efficacy due to secondary failure in infliximab or primary failure in adalimumab. To increase treatment efficacy, it will be necessary for these patients to use an additional concomitant treatment. Higher efficacy is expected with biologics than with conventional treatments; however, the actual clinical efficacy over a long period of time may be insufficient if they are used without any concomitant treatments.     

Efficacy comparison of ustekinumab between anti‐tumor necrosis factor‐α drug‐naïve and anti‐tumor necrosis factor‐α drug‐resistant Japanese psoriasis cases

Ustekinumab is highly efficacious for psoriasis; however, it has not been fully clarified whether previous failure in anti‐tumor necrosis factor‐α (TNF‐α) therapy affects the treatment response with ustekinumab. Therefore, we evaluated the efficacy of ustekinumab in anti‐TNF‐α‐naïve and anti‐TNF‐α‐resistant cases and compared the clinical efficacies of adalimumab and ustekinumab in biologic naïve cases. Thirty‐five patients with plaque psoriasis who showed resistance to conventional therapies were enrolled; 26 patients, who had never been treated with biologics, were allocated to ustekinumab or adalimumab; nine patients who failed to achieve psoriasis area and severity index (PASI) 50 at week 16 with one or two TNF‐α antagonists were switched to ustekinumab. The end of the study was defined as 52 weeks after starting the first biologic for anti‐TNF‐α‐naïve patients and after switching to ustekinumab for anti‐TNF‐α‐resistant patients. The primary outcome measurement was the percentage of patients achieving PASI75 at week 16. In patients treated with ustekinumab, 87.5% of anti‐TNF‐α‐naïve and 77.8% of anti‐TNF‐α‐resistant cases achieved a PASI75 response at week 16, and no statistically significant difference was found between the treatment response rates (P = 0.60). When comparing the treatment efficacy of ustekinumab and adalimumab among anti‐TNF‐α‐naïve patients, there was also no statistically significant difference in PASI75 achievement rates (87.5 vs. 83.3%, P = 0.79). Our study suggests that ustekinumab can be considered as a first‐line biologic for psoriasis and a rescue therapy for anti‐TNF‐α‐resistant cases.     

Economic evaluation of systemic therapies for moderate to severe psoriasis

Background New biologics have dramatically changed therapeutic options for psoriasis, albeit at additional cost. Objectives To determine the cost‐effectiveness and optimal treatment sequence for moderate to severe psoriasis. Methods Psoriasis Area and Severity Index (PASI) response rates from 22 randomized controlled trials evaluating biologic (adalimumab, efalizumab, etanercept, infliximab) and nonbiologic systemic (methotrexate, ciclosporin) agents were considered. Short‐term efficacy was based on relative probabilities of achieving PASI response (50/75/90) in a meta‐analysis of trials. Published evidence and assumptions were used to predict long‐term efficacy. Treatment benefits were determined by the relationship between PASI response and the EuroQOL 5D health utility measure. Costs included therapy, administration, monitoring and hospitalization. Incremental cost‐effectiveness ratios (ICERs) were calculated and treatments ranked relative to supportive care. Results Infliximab provided the most incremental quality‐adjusted life‐years (QALYs) vs. supportive care (0·18 QALYs; 95% confidence interval, CI 0·13–0·24), followed by adalimumab (0·16 QALYs; 95% CI 0·11–0·22). Methotrexate and ciclosporin were less beneficial (0·13 and 0·08 QALYs, respectively) but were cost saving and considered the first two treatments in the optimal sequence. Comparing biologics, adalimumab was most cost effective (ICER £30 000 per QALY), followed by etanercept (£37 000 per QALY), efalizumab (£40 000 per QALY) and infliximab (£42 000 per QALY). Conclusions Methotrexate and ciclosporin are cost effective but require monitoring for toxicities. Of the biologics, adalimumab was most cost effective following conventional systemic treatment failure or inadequate response. Payers and policymakers will have to decide how to utilize their budgets effectively for treating patients with moderate to severe psoriasis.     

Safety,efficacy and drug survival of biologics and biosimilars for moderate‐to‐severe plaque psoriasis

Psoriasis, a common disease affecting 2‐3% of the world's population, may in moderate‐to‐severe cases require systemic treatment with biological drugs (biologics). Treatment is usually permanent, but these drugs may loose their effect over time. When the patent for the original (originator) drug expires, other companies can produce a biosimilar, i.e. a drug that is very similar (but not completely identical, since biologics are derived from living human genes) to the originator. This Danish study compared safety, efficacy, and drug survival (i.e. how long patients stay on therapy) for five biologics: adalimumab, etanercept, infliximab, secukinumab, and ustekinumab. The study also compared the originator versions of etanercept and infliximab to their biosimilar versions. Data was examined from 3495 treatment series in 2161 patients. Drug survival was significantly higher for ustekinumab than for the other drugs. Secukinumab had the shortest survival and thereby also the highest risk of discontinuation of therapy. Adverse events also occurred the most frequently with secukinumab. Switching from an originator to a biosimilar version did not significantly affect drug survival. Among patients that obtained complete skin clearance, this occurred more rapidly for those treated with secukinumab as their first‐ever biologic. Over a 10‐year period, discontinuation of therapy occurred in 45·7% (adalimumab), 64·9% (etanercept), and 54·4% (infliximab) of patients. Ustekinumab and secukinumab have only been available for 8 and 2 years, respectively, during which time 30·3% and 28·8% of patients discontinued these therapies, respectively. Over time, response to therapy was generally highest for ustekinumab, followed by adalimumab.     

Biologic Response Modifiers and Pediatric Psoriasis

The efficacy and safety of biologic response modifiers such as etanercept, adalimumab, infliximab, and ustekinumab have been demonstrated in the treatment of psoriasis in adults, but none are currently approved for the treatment of psoriasis in children in the United States, and only etanercept is approved for the treatment of psoriasis in children in the European Union. Through case reports, case series, and a large clinical trial of the use of etanercept, the literature supports the use of these agents to treat psoriasis in children. Data on the use of the tumor necrosis factor‐α antagonists etanercept, adalimumab, and infliximab in the treatment of other inflammatory diseases in children—namely Crohn's disease, juvenile arthritis, and uveitis—support their safety profile in children.     

Obesity and psoriasis: body weight and body mass index influence the response to biological treatment

Patients with psoriasis, in particular those requiring systemic treatment, tend to be above normal weight. Obesity is associated with psoriasis and contributes significantly to the increased cardiovascular risk in these patients. Most biologics used to treat psoriasis in the European Union are fixed dosed treatments: etanercept, adalimumab and ustekinumab. Apart from infliximab, dosing regimens do not account for weight, with the exception of ustekinumab, the dose of which should be doubled in patients weighing more than 100 kg. The aim of this study was to review the available evidence on the association of obesity and psoriasis, and the effect of body weight or obesity on the efficacy of biologics as well as their practical implications in daily practice. A review was performed of the literature relating to obesity and psoriasis and weight effect, including subgroup analyses, on the efficacy of the biologicals available for treatment of psoriasis in the European Union, namely adalimumab, etanercept, infliximab and ustekinumab. Optimal responses with fixed dose biological agents are less frequent in patients with increasing weight, especially above 100 kg, who account for approximately 25% to 30% of patients in clinical trials. Body weight effect on drug clearance might partly account for this fact. The data are limited to subgroup analyses, often with no statistical significance reported. Further studies, including weight‐based subanalysis of clinical trials and pharmacoeconomic evaluations, are required to assess the issue of body weight and response to therapy of the biologics. Infliximab response appears to be independent of body mass index. Possible weight‐based dose adjustments and the impact of treatment on body weight changes also require additional study.