Eficiencia de los agentes biológicos en el tratamiento de la psoriasis moderada-grave

BackgroundIn the treatment of psoriasis, biologic agents are more expensive than conventional therapy while showing similar or superior efficacy. However, their efficiency in terms of cost/efficacy (cost per responder in clinical trial conditions) is unknown.ObjectiveTo estimate the cost/efficacy ratios of adalimumab, etanercept, infliximab, and efalizumab in the management of moderate to severe psoriasis.Material and MethodsA model for the costs analysis was elaborated by building a decision tree for each of the treatments for which scientific evidence was available. The payer perspective (Spanish national health system) was used, only considering drug costs. The efficacy (proportion of patients who respond according to Psoriasis Area Severity Index [PASI] 75 criterion) was assigned according to the results of the clinical trials. When more than 1 trial was available per treatment, a meta-analysis was undertaken. In the case of weight-dependent dosing, the weight of the study participants was adjusted by age and sex to the standard Spanish population with correction for increased weight in individuals with psoriasis. Uncertainty was investigated with a sensitivity analysis.Results and ConclusionsAssigning the efficacy reported in the 15 published clinical trials, the most efficient biologic agent in terms of the cost/efficacy ratio was adalimumab, with one PASI 75 response at a cost of €8,013. For the remaining biologic agents and with different regimens, the cost per responder ranged from €9,370 to €17,112. The sensitivity analysis confirmed the robustness of these figures.     

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.     

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.     

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.     

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.     

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.     

Systematic review on the maintenance of response during systemic antipsoriatic therapy

As a chronic disease psoriasis often requires long‐term treatment. Successful continuation of therapy during a maintenance phase is therefore important. A systematic review was performed on the efficacy of psoriasis drugs during maintenance treatment in patients who had achieved sufficient treatment success during the induction period. Maintenance therapy is defined as treatment during the period after successful induction therapy. Inclusion criteria were prospective studies with systemic therapies recommended by the 2009 European psoriasis guidelines (plus ustekinumab), and a study population that had achieved a defined treatment response criterion after induction therapy within a period of ≥ 6 months. Maintenance studies on conventional treatments were identified for ciclosporin (CSA) only (no studies investigating acitretin, methotrexate or ustekinumab were found). Compared with placebo, CSA was shown to be effective in maintenance therapy, yet CSA 1·5 mg kg^?1 seems to be insufficient to maintain disease control. Based on the evidence, it is uncertain whether there is any difference between daily or intermittent treatment. For biologics, maintenance data were available for adalimumab, etanercept and infliximab. No differences in 75% improvement in Psoriasis Area and Severity Index (PASI 75) response were identified between adalimumab 40 mg once and twice a month. Continuous infliximab treatment was shown to be superior to as‐needed treatment. For etanercept, only observational postrandomized controlled trial data were available, indicating a maintained PASI 75 response in approximately three‐quarters of patients during long‐term treatment. Only limited evidence is available for a conclusion on how patients with an adequate response should be optimally treated during the maintenance period. A clear ranking of the available treatments is not yet possible.     

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.     

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.     

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.     

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.     

Efficacy and safety of systemic treatments for moderate‐to‐severe psoriasis: meta‐analysis of randomized controlled trials

Dermatologists may choose from various conventional and biological systemic agents to treat patients with moderate‐to‐severe psoriasis. We set out to analyse systematically the efficacy and tolerability of approved treatments for moderate‐to‐severe psoriasis. We undertook a systematic review and meta‐analysis of randomized controlled trials (RCTs) investigating the efficacy of systemic treatment approved for moderate‐to‐severe psoriasis. Efficacy was assessed as the proportion of participants with 75% improvement in Psoriasis Area and Severity Index at primary efficacy measurement (week 8–16). Safety was summarized as rates of adverse events and withdrawals. Direct and indirect comparative efficacy was assessed by random effects meta‐analysis of risk differences (RDs). In total, 48 eligible RCTs totalling 16 696 patients (11 178 randomized to biologics, 1888 to conventional treatments) were identified. In placebo‐controlled trials, infliximab was the most efficacious [RD 76%, 95% confidence interval (CI) 73–79%]. Adalimumab (RD 61%, 95% CI 56–67%), and ustekinumab 45 mg (RD 63%, 95% CI 59–66%) and 90 mg (RD 67%, 95% CI 60–74%) each had similar efficacy. These biologics are more effective than etanercept and all conventional treatments. Head‐to‐head trials indicate the superiority of adalimumab and infliximab over methotrexate (MTX), the superiority of ustekinumab over etanercept, the nonsignificant superiority of ciclosporin over MTX, and the dose‐dependent efficacy of etanercept and ustekinumab. Fumaric acid is as efficacious as MTX. Safety of treatments could not be pooled due to a lack of standardization in reporting across trials. In conclusion, the qualitative and quantitative evidence is much stronger for biological interventions than for conventional treatments.     

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.     

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.     

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.     

Biologic treatment sequences for plaque psoriasis: a cost–utility analysis based on 10 years of Dutch real‐world evidence from BioCAPTURE

Psoriasis is a chronic inflammatory skin condition. It can be unsightly and uncomfortable, significantly affecting quality of life. It is usually treated with regular applications of creams, but more severe psoriasis requires immune‐suppressive medication given by mouth or injection. Newer, targeted “biologic” drugs are more effective but expensive, and cost‐benefit data is limited. Patients in the real world often differ from those selected for randomised control trials (RCTs) in having additional illnesses, and are often switched from one drug to another to improve efficacy or reduce side‐effects; there is no evidence to inform clinicians about what order to use them in. This industry‐sponsored study from Holland analysed the cost‐effectiveness of three biologic drugs, adalimumab, etanercept and ustekinumab, given in different sequences over 10 years. A computerised simulation used published information on drug and monitoring costs and “real world evidence” from 318 patients already enrolled in a Dutch registry called BioCAPTURE (Continuous Assessment of Psoriasis Treatment Use Registry with Biologics) which includes quality of life scores as well as clinical outcomes (i.e. symptoms) and details of treatment. Mean age at enrolment was 47 years, mean body weight 87 kg and mean biologic treatment course duration 29.6 months. They estimated that treatment of psoriasis with these biologics for ten years costs €141,962 to €148,442 per patient. Starting with adalimumab or ustekinumab rather than etanercept costs somewhat less for each additional year in perfect health, even when modelled using cheaper “biosimilars”, and is thus considered advantageous in health‐economic terms, at least within an academic centre.     

Plasma trough levels of adalimumab and infliximab in terms of clinical efficacy during the treatment of psoriasis

We examined the relation between adalimumab and infliximab plasma trough levels, anti‐adalimumab and anti‐infliximab antibody formation. We analyzed plasma from 32 adalimumab‐treated and 20 infliximab‐treated psoriasis patients for evaluating trough levels of each drug. The presence of anti‐adalimumab and anti‐infliximab antibodies was analyzed and the severity of psoriasis was evaluated. At week 28, 25 out of 32 and at week 48, 21 out of 30 adalimumab‐treated patients maintained as more than PASI 75. At week 28, 12 out of 20 and at week 48, nine out of 18 infliximab‐treated patients were evaluated as more than PASI 75. In patients treated with 40 mg adalimumab every other week, the mean trough level was 7.62 μg/mL (range, 0.05–10.6) at week 48. In patients treated with 80 mg adalimumab every other week, the mean trough level was 8.61 μg/mL (range, 0.08–13.5) at week 48. Mean trough level of infliximab‐treated cases (4.1–5.2 mg/kg; mean, 4.6) was 4.64 μg/mL (range, 0.03–16.9) at week 48. Anti‐adalimumab antibody was detected in five out of 32 cases and anti‐infliximab antibody was detected in six out of 20 cases, respectively, at weeks 24 and 48. The optimal cut‐off values of adalimumab and infliximab concentration for more than PASI 75 were more than 7.84 μg/mL and more than 0.92 μg/mL, respectively. The trough levels of adalimumab and infliximab in psoriasis patients were positively associated with clinical response and were significantly lower in cases having anti‐adalimumab or anti‐infliximab antibodies.     

Comparative Efficacy of Biologics in Psoriasis

Background: Psoriasis is a chronic, immune-mediated skin disease that also has systemic manifestations. Safe and effective long-term treatments are needed. Biologic treatments that inhibit the immunopatho-genesis of psoriasis have helped meet this need. Purpose: The purpose of this study was to compare the efficacy of biologic therapies used for psoriasis. Methods: A literature search was performed using PubMed and the keywords ‘(PASI-75 OR efficacy) AND psoriasis AND (adalimumab OR alefacept OR etanercept OR infliximab OR ustekinumab).’ Randomized, double-blind, and placebo-controlled studies on US FDA-approved biologics were selected. Studies assessing the proportion of subjects achieving 75% improvement in Psoriasis Area and Severity Index (PASI-75) within a 12-week period were included. Studies on pediatric populations and psoriatic arthritis were excluded. The weighted average of PASI-75 for each reported regimen was calculated to determine the efficacy of biologic agents used for moderate-to-severe psoriasis. Tolerance and secondary efficacy measures were also examined for the selected studies. Results: FDA-approved regimens of adalimumab, infliximab, ustekinumab, and alefacept were effective in treating moderate-to-severe psoriasis. Weighted average PASI-75 scores for infliximab, ustekinumab, adalimumab, etanercept, and alefacept were 78.6%, 72.1%, 70.5%, 48.1%, and 21%, respectively. Limitations: The comparative efficacy of biologic agents data was limited to 12 weeks, thus generalizing the results to longer treatment periods may not be accurate. Conclusions: Various biologic agents for psoriasis were effective at 12 weeks in placebo-controlled trials. Available data cannot fully account for situations in clinical practice, in which combination and longer duration of therapy may be required. When choosing the most effective or best agent, multiple factors should be considered including patient preference, cost, tolerance, adverse effects, dosing schedule, and mode of administration.     

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

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

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.