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.     

Efficacy and safety of adalimumab in patients with psoriasis previously treated with anti‐tumour necrosis factor agents: subanalysis of BELIEVE

Background Few large clinical studies have evaluated whether switching tumour necrosis factor antagonists (anti‐TNFs) is likely to improve psoriasis in patients with prior anti‐TNF treatment. Objective The aim of this subanalysis of the BELIEVE study was to assess the efficacy and safety of adalimumab for psoriasis in patients with and without previous anti‐TNF treatment. Methods The BELIEVE study enrolled patients with moderate to severe psoriasis and prior failure, intolerance or contraindication to ≥2 systemic therapies. In this 16‐week, double‐blind, randomized, controlled trial, patients received adalimumab (80 mg, week 0; 40 mg every other week, weeks 1–15) with either topical vehicle or topical calcipotriol/betamethasone dipropionate (C/B) applied once daily for 4 weeks, then as needed. The primary endpoint was ≥75% improvement from baseline in Psoriasis Area and Severity Index score (PASI 75) at week 16. This post hoc subanalysis evaluated the safety and efficacy of adalimumab, with and without topical therapy, in BELIEVE patients who had prior exposure to anti‐TNFs. Results Of 730 patients enrolled, 282 (38.6%) had prior anti‐TNFs and 448 (61.4%) were anti‐TNF‐naïve. Combining topical vehicle and topical C/B study populations, 61.7% of patients with prior anti‐TNFs achieved PASI 75 at week 16, compared with 71.7% of anti‐TNF‐naïve patients (P = 0.095). Adalimumab resulted in clinically meaningful improvement regardless of which prior anti‐TNF agent had been used, the number of prior anti‐TNFs tried, or reasons for discontinuation of prior anti‐TNF therapy. Adverse event incidences were similar between patients with and without prior anti‐TNF therapy. Conclusion Adalimumab was effective and well‐tolerated in patients with psoriasis previously treated with anti‐TNF therapy.     

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.     

Ustekinumab in clinical practice: response depends on dose and previous treatment

Objectives To evaluate the efficacy of ustekinumab in a series of patients with moderate to severe psoriasis treated according to the European Medicines Agency (EMA) label and to identify factors such as dose, baseline PASI or previous treatment potentially related to therapeutic outcome. Methods Retrospective review of the clinical records from 36 consecutive patients treated with ustekinumab during at least 36 weeks at a single referral center. Candidates for treatment had a PASI ≥ 10 or a BSA ≥ 10 and either failure to respond to, or a contraindication to, or intolerance to some systemic or another biologic treatment. The main outcome measures were PASI improvement with respect to baseline at weeks 12 and 24 (prior to the third injection of ustekinumab). Results Overall 75%, 69%, and 86% patients achieved PASI75 response rates at weeks 12, 24 and 36, respectively. Patients weighing ≤ 100 kg and treated with 45 mg doses had better PASI 50, PASI75 and PASI90 response rates than heavier patients (treated with 90 mg) at every point in time, and the differences were statistically significant at week 24. PASI75 response rates at week 24 were significantly better in patients with no prior exposure to TNFα blocking agents (85% vs. 50%, P = 0.0235). Conclusions In clinical practice, ustekinumab is effective both in biologic‐naÿve patients and as salvage therapy when other biological treatments have failed. The response rates prior to the third injection in our series were better in patients weighing ≤ 100 kg and in those without previous exposure to biologics.     

Clinical predictors of nonresponse to anti‐TNF‐α agents in psoriatic patients: A retrospective study

Although the heterogeneity of the therapeutic response to TNF‐α blockers seems to be mainly due to genetic factors, several studies showed that a range of factors may influence it. The aim of our study was to investigate the impact of patients' demographic and clinical characteristics on primary response to an anti‐TNF‐α therapy in psoriatic patients. We retrospectively examined the relationship between various clinical and demographic features and response to treatment with etanercept, adalimumab, and infliximab, evaluated as PASI75 and average PASI improvement at weeks 12, 16, and 14, respectively. We analyzed data obtained from 199 patients. A better response to the treatment was significantly associated with male gender (OR = 2.59), coexistence of psoriatic arthritis (OR = 1.97), and PASI ≤15 at baseline (OR = 0.91). The present study supports that some clinical factors may be potential predictors of response to anti‐TNF‐α agents in psoriatic patients.     

Adalimumab therapy for psoriasis in real‐world practice: efficacy,safety and results in biologic‐naïve vs. non‐naïve patients

Background Patients and the course of treatment in daily practice are different from randomized controlled trials (RCTs). Objectives Primary objective: to analyse the percentage of patients achieving PASI 75. Secondary objectives: PASI 50, PASI 90, PASI 100 responses, the percentage of patients experiencing at least one serious adverse event (SAE) and the response in biologic‐naïve vs. non‐naïve patients. Methods Prospectively collected efficacy and safety data of a cohort of psoriasis patients treated with adalimumab in daily practice between May 2007 and July 2011 were analyzed. Efficacy was determined using an intention‐to‐treat analysis and an as treated analysis, in comparison with the course baseline PASI before the start of adalimumab and the original baseline PASI before the start of any biologic therapy. Results Eighty‐five patients received adalimumab therapy with a mean treatment duration of 1.4 (range 0.02–3.1) years. Compared with the original baseline PASI, PASI 75 response rates at week 12 and 24 were 34% and 38% (ITT). PASI 75 responses were well maintained until week 132. Only the PASI 75 response rate at week 12 differed significantly between biologic‐naïve (56%) and non‐naïve patients (29%). Sixteen patients (19%) experienced 28 SAEs. Seven patients (8%) experienced SAEs considered possibly or probably related to adalimumab. Conclusions In this cohort, PASI75 responses were substantial but lower than in RCTs and other daily practice studies. Efficacy was well maintained during more than 2 years of follow‐up and differed only between biologic‐naïve and non‐naïve patients at week 12. The incidence of SAEs was low but seems higher than observed in RCTs.     

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.     

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.     

Safety of anti‐tumour necrosis factor‐α agents in psoriasis patients who were chronic hepatitis B carriers: a retrospective report of seven patients and brief review of the literature

Background Issues concerning the potential risks of reactivating chronic hepatitis B virus arise when the use of anti‐Tumour Necrosis Factor‐α (TNFα) agents is imperative in patients with concurrent psoriasis and hepatitis B virus infection. Objective The aim of this study was to report the experience regarding safety in the management of patients with coexisting psoriasis and chronic hepatitis B with the anti‐TNFα agents: infliximab, etanercept and adalimumab. Methods The psoriasis outpatient database of our dermatological department was searched for psoriasis and hepatitis B diagnoses and the medical records of these patients were reviewed for use of anti‐TNFα agents. Results Seven cases (four women and three men) were identified, with mean age of 51 years (34–65 years). Three patients received adalimumab, three patients were given etanercept and one infliximab. All patients received lamivudin, 100 mg/day, which started 2 weeks before the initiation of anti‐TNFα medication and went on during the whole treatment period. Follow‐up period extended from 6–24 months. All patients were inactive HbsAg (+) carriers. Liver function tests – at baseline and at the end of follow‐up period – were within the normal range. There was no considerable rise in the viral load in any case, from baseline until the last available measurement, although a patient receiving infliximab showed an increase that reached 600 IU/mL. Conclusion Successful treatment of psoriasis with anti‐TNFα agents in patients who are inactive HBsAg carriers is possible and could be safe under the conditions of concomitant lamivudin administration and intensive monitoring. Larger randomized controlled studies are needed to confirm these findings.     

Comparison of drug survival rates for adalimumab, etanercept and infliximab in patients with psoriasis vulgaris

Background Adherence to treatment is an indicator of treatment success. Long‐term data on adherence to biologic treatment in psoriasis are lacking. Objectives To compare the tumour necrosis factor (TNF)‐α inhibitors regarding drug survival rate and safety in patients with psoriasis. Methods This study is based on data from the Danish nationwide database DERMBIO covering patients with psoriasis treated with a biologic agent. All patients who received anti‐TNF‐α treatment in academic referral centres were included. Baseline data, adverse events, time on treatment and reason for stopping treatment were recorded. Hazard ratios (HRs) for factors determining drug survival were calculated by logistic regression. Results In total, 882 treatment series with etanercept (n = 311), adalimumab (n = 427) or infliximab (n = 144) were administered to 747 patients. Significant predictors of drug survival were: sex, the anti‐TNF‐α agent and the previous response to an anti‐TNF‐α agent. In the group of anti‐TNF‐α‐naïve patients the longest drug survival was observed for infliximab, followed by adalimumab [HR vs. infliximab 3·70, 95% confidence interval (CI) 1·99–6·89] and etanercept (HR vs. infliximab 3·18, 95% CI 1·72–5·86). The 4‐year drug survival is in the range of 40% for etanercept or adalimumab vs. 70% for infliximab. There was no difference in number of adverse events. Conclusions The overall efficacy of anti‐TNF‐α drugs diminishes with time, as envisaged by the progressive loss of patient adherence to treatment. The major reasons for stopping treatment were loss of efficacy, followed by adverse events. Infliximab had the best patient retention ability, with 70% of patients still being on the drug after 4 years 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.     

Effects of anti‐TNF‐α agents on circulating endothelial‐derived and platelet‐derived microparticles in psoriasis

Psoriasis involves TNF‐α secretion leading to release of microparticles into the bloodstream. We investigated the effect of TNF blockers on microparticles levels before and after treatment in patients (twenty treated by anti‐TNF‐α agents and 6 by methotrexate) with severe psoriasis. Plasmatic microparticles were labelled using fluorescent monoclonal antibodies and were analysed using cytometry. Three months later, 70% of patients treated with anti‐TNF‐α agents achieved a reduction in PASI score of at least 75%. The clinical improvement in patients treated with anti‐TNF‐α agents was associated with a significant reduction of the mean number of platelet microparticles (2837/μl vs 1849/μl, P = 0.02) and of endothelial microparticles (64/μl vs 22/μl, P = 0.001). Microparticles are significantly decreased in psoriatic patients successfully treated by anti‐TNF‐α. Microparticles levels as circulating endothelial cells represent signs of endothelial dysfunction and are elevated in psoriasis. Then, TNF blockade may be effective to reduce cardiovascular risk through the reduction of circulating microparticles.     

Benefit‐risk assessment of tumour necrosis factor antagonists in the treatment of psoriasis

Background Safety of tumour necrosis factor (TNF) antagonists is a primary concern for clinicians prescribing them to patients with psoriasis. Objectives To determine the benefit‐risk balance of TNF antagonists in psoriasis. Methods Through integrated analyses of published literature, we calculated the number needed to treat (NNT) for various efficacy measures and the number needed to harm (NNH) for various adverse events for approved dosing regimens of adalimumab, etanercept and infliximab. Integrated analyses that included open‐label safety data from TNF‐antagonist clinical trials were also conducted. Results PASI 75 treatment effect data from the literature result in NNT values of 1·6 (95% confidence interval, CI 1·5–1·7) for adalimumab 40 mg every other week; 3·2 (95% CI 2·8–3·7) for etanercept 50 mg weekly or 25 mg twice weekly, and 2·3 (95% CI 2·1–2·5) for etanercept 50 mg twice weekly; and 1·4 (95% CI 1·3–1·5) for infliximab 5 mg kg^?1 dosing. For serious noninfectious, serious infectious and malignant adverse events, point estimates of the NNHs are generally at least two orders of magnitude larger than the NNTs, and the 95% CIs for the NNHs for adalimumab, etanercept and infliximab overlap. Analyses that included open‐label data corroborated, with increased exposure to study agents, the low risk of adverse events observed in placebo‐controlled periods. Conclusions These analyses demonstrated that, during the initial year of treatment, the likelihood of success with anti‐TNF therapy for psoriasis was several orders of magnitude greater than the likelihood of serious toxicity.     

Development of MGUS in psoriatic patients: a possible undiagnosed event during anti‐TNF‐α‐treatment

Background Monoclonal gammopathies are haematological conditions characterized by the clonal proliferation of plasma cells which produce a monoclonal immunoglobulin that accumulates in the blood. They have already been reported during treatment with a range of drugs but never before during treatment with the anti‐TNF‐α treatments: adalimumab, etanercept and infliximab currently used in the therapy of moderate‐severe psoriasis and psoriatic arthritis. Objective This is a case series describing the development of MGUS in psoriatic patients treated with anti‐TNF‐α. Methods Three hundred patients receiving an anti‐TNF‐α treatment for chronic plaque psoriasis or psoriatic arthritis in a clinical setting in Italy, These patients were screened through serum protein electrophoresis to investigate the possible development of MGUS. Results Eight patients were found to have developed monoclonal gammopathy of undetermined significance. The median treatment duration for the eight patients was 1 year with excessive IgG present in five patients, IgM accumulation in one patient and a double monoclonal component in two patients. Conclusion Our data suggest that there may be an association between anti‐TNF‐α therapy and development of MGUS.     

Relationship between the efficacy of biologics and clinical plaque psoriasis subtypes in Japanese patients: A single‐center pilot study

Although biologics for plaque psoriasis brought epoch‐making efficacy, not all patients achieve treatment success with all reagents. The aim of this study was to clarify the correlation between clinical plaque psoriasis subtypes, age at onset, and the efficacy of biologics. Clinical records for patients with plaque psoriasis at Fukuoka University Hospital were reviewed retrospectively. The efficacy of biologics was compared using the survival of the first biologics administered in treatment‐naïve patients. The survival of infliximab, adalimumab, and ustekinumab were followed until December 2016. The patients were clinically classified into three subtypes: small, large, or gigantic plaques using the size of the plaques on the back; early onset psoriasis (EOP, onset <40 years); or late‐onset psoriasis (LOP, ≥40 years). Eighty‐seven patients were enrolled. The survival of biologics was significantly better in large plaques compared with small or gigantic plaques (P = 0.0007). In patients treated with tumor necrosis factor (TNF) inhibitors, large plaques had significantly better survival than did the other types (P = 0.0122), while ustekinumab showed good survival in all three subtypes. The survival of biologics was numerically better in EOP than in LOP, but this was not significant. The efficacy of TNF inhibitors was different among clinical subtypes. Psoriatic patients with small plaques may be less responsive to TNF inhibitors. Further studies are needed.     

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.     

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.     

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.     

Long‐term efficacy of ustekinumab in patients with moderate‐to‐severe psoriasis treated for up to 5 years in the PHOENIX 1 study

Background Ongoing evaluation of biological agents in patients with moderate‐to‐severe psoriasis is needed to support their long‐term use. Objective To evaluate long‐term efficacy and safety of ustekinumab through 5 years in the PHOENIX 1 study. Methods Patients were randomized to placebo or ustekinumab (45 mg or 90 mg) at Weeks 0, 4 and every‐12‐weeks thereafter; placebo patients crossed‐over to ustekinumab at Week 12. Clinical response through Week 244 was evaluated using the Psoriasis Area and Severity Index (PASI) in the Overall Population (i.e. patients receiving ≥1 dose of ustekinumab), Initial Responders (i.e. PASI 75 responders [Weeks 28/40] re‐randomized at Week 40 to continue every‐12‐week maintenance) and Partial Responders (i.e. <PASI 75 responders adjusted to every‐8‐week maintenance at Weeks 28 or 40). Safety endpoints were evaluated through Week 264 for the Overall Population. Results  Overall, 68.7% (517/753) of ustekinumab‐treated patients completed treatment through Week 244. Initial clinical responses were generally maintained through Week 244 (PASI 75: 63.4% and 72.0%; PASI 90: 39.7% and 49.0%; PASI 100: 21.6% and 26.4%) for patients receiving 45 mg and 90 mg, respectively. Similarly, PASI 75 responses were generally maintained among Initial Responders [79.1% (45 mg) and 80.8% (90 mg)] and Partial Responders [57.6% (45 mg) and 55.1% (90 mg)]. With 3104 patient‐years of follow‐up, rates of overall adverse events (AEs), serious AEs, serious infections, malignancies and major adverse cardiovascular events were generally consistent over time and comparable between doses. Conclusions Through 5 years of continuous treatment, ustekinumab demonstrated stable clinical response and a safety profile consistent with previous reports.