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.     

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.     

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.     

Fluctuations in serum levels of adalimumab and infliximab in patients on stable treatment for psoriasis

Many patients with psoriasis fail to respond to biologic drugs either initially or lose response over time, the latter having predominantly been linked to low circulating drug levels. We examined how serum drug levels varied over three treatment cycles of stable maintenance therapy with either adalimumab or infliximab among a total of 28 patients with psoriasis (22 men, mean age 48.6 years, mean treatment time 6.2 years) and whether there was an association with various patient‐specific factors. The range for all concentrations was 1.1 to 24.3 μg/mL for adalimumab and 0.0 to 180.6 μg/mL for infliximab. There was a consistent inverse association between body mass index (BMI) and trough and maximum serum concentrations of adalimumab (P < .05 for all comparisons) and a positive, less consistent, association between age and maximum serum concentration of infliximab (P < .05 for both comparisons). Patient‐specific factors, such as BMI and age, can help predict fluctuations in serum concentrations of biologics used for psoriasis.     

Adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis: Efficacy and safety results from a Phase II/III randomized controlled study

Incidence of psoriasis vulgaris in Asians is estimated at 0.05–0.3%. Studies in North America and Europe demonstrated that adalimumab, a fully human, recombinant, immunoglobulin G₁ monoclonal antibody, was efficacious and well‐tolerated in patients with chronic plaque psoriasis. This 24‐week, placebo‐controlled study evaluated the efficacy and safety of three different dosing regimens of adalimumab in Japanese patients with moderate to severe chronic plaque psoriasis (n = 169). Patients were randomized to receive adalimumab 40 mg every other week (eow), adalimumab 80‐mg loading dose at week 0 followed by adalimumab 40 mg eow starting at week 2, adalimumab 80 mg eow, or placebo eow given as s.c. injections. The primary efficacy endpoint was the percentage of patients achieving a 75% or greater improvement in Psoriasis Area and Severity Index (PASI 75) score at week 16. At week 16, PASI 75 response rates were significantly greater for all three adalimumab groups (40 mg eow: 57.9%, P < 0.001; 40 mg eow plus loading dose: 62.8%, P < 0.001; 80 mg eow: 81.0%, P < 0.001) versus placebo (4.3%). As early as week 4, the 40‐mg eow plus loading dose and 80‐mg eow groups achieved significantly greater PASI 75 response rates compared with placebo. Injection‐site reactions and hepatic events occurred in greater percentages of adalimumab‐treated patients compared with placebo. Adalimumab therapy demonstrated efficacy and safety at all three dosage regimens. Rapid response rate in patients receiving 40 mg eow plus loading dose supports using an 80‐mg loading dose in the treatment of psoriasis.     

Adalimumab treatment optimization for psoriasis: Results of a long‐term phase 2/3 Japanese study

The tumor necrosis factor‐α inhibitor, adalimumab, is approved to treat moderate‐to‐severe plaque psoriasis (40 mg every‐other‐week or 80 mg every‐other‐week following inadequate response at 40 mg in Japan). This open‐label extension (OLE) trial evaluated the optimal adalimumab dose for long‐term efficacy and safety in Japanese patients with moderate‐to‐severe plaque psoriasis following a prior 24‐week, phase 2/3, randomized, double‐blind study. Of the 169 patients from the phase 2/3 trial, 147 entered the OLE on 40 mg (n = 89) or 80 mg (n = 58) adalimumab every‐other‐week. Patients on 40 mg with Psoriasis Area and Severity Index (PASI) of less than 50 could escalate to 80 mg. At week 52 (28 of OLE), patients entering the OLE on 80 mg were reduced to 40 mg, with the option to re‐escalate. For patients entering the OLE on 40 mg, final PASI 50/75/90 response rates were 85.1%/73.3%/60.4%, respectively, including effects of dose escalation. Among patients whose dose was escalated, final PASI 50/75/90 response rates were 70.0%/53.3%/36.7%, respectively. For patients entering the OLE on 80 mg, final PASI 50/75/90 response rates were 92.5%/84.9%/73.6%, respectively, including effects of dose re‐escalation. Overall incidence rates of adverse events (AE) and injection‐site reaction AE declined over time; rates for serious AE and infections were generally stable. Clinically meaningful efficacy of adalimumab was sustained to 4 years. Dose escalation to 80 mg every‐other‐week for patients with suboptimal response to 40 mg every‐other‐week, and dose reduction to 40 mg every‐other‐week for patients satisfactorily controlled on 80 mg every‐other‐week, are viable strategies for adalimumab optimization.     

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.     

Dramatic impact of a Psoriasis Area and Severity Index 90 response on the quality of life in patients with psoriasis: an analysis of Japanese clinical trials of infliximab

European S3 Guidelines on the systemic treatment of psoriasis in 2009 propose 75% or more improvement in the Psoriasis Area and Severity Index from baseline (PASI 75) and a Dermatology Life Quality Index (DLQI) of 0 or 1 as treatment goals. However, the relationship of these two parameters is yet to be clarified. Herein, we analyzed the data pooled from two Japanese phase III clinical trials on psoriasis with infliximab to clarify the PASI response necessary to achieve a DLQI of 0 or 1. Of the 90 patients, the mean percent improvement in PASI at week 50 or 66 was 74.5%, and the PASI 75 and PASI 90 response rates were 66.7% and 46.7%, respectively; no difference in the improvement was noted among the body areas. Significant improvements in nail psoriasis were also observed. A negative correlation was shown between the improvement in PASI and DLQI. Patients who achieved a PASI 90 response had a significantly higher percentage of achieving a DLQI of 0 or 1 than the patients who achieved a PASI 75 but not a PASI 90 response. The median serum trough level of infliximab was maintained at 2 μg/mL or more in the PASI 90 responders, whereas it was less than 1 μg/mL at week 30 and on in the others. The present results demonstrate that a PASI 90 response is necessary to achieve a DLQI of 0 or 1. Infliximab is considered a useful drug in meeting the treatment goal of achieving a DLQI of 0 or 1 through the attainment of a PASI 90 response.     

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 infliximab vs. methotrexate in patients with moderate-to-severe plaque psoriasis: results of an open-label, active-controlled, randomized trial (RESTORE1)

Background Infliximab is indicated for treatment of moderate‐to‐severe plaque psoriasis in adults whose disease cannot be controlled with other systemic therapies, including methotrexate (MTX). To date, no studies have directly compared the efficacy and safety of infliximab and MTX. Objectives To compare the efficacy and safety of infliximab vs. MTX in adults with moderate‐to‐severe plaque psoriasis. Methods MTX‐naïve patients (n = 868) were randomized 3 : 1 to receive infliximab 5 mg kg^?1 at weeks 0, 2, 6, 14 and 22 or MTX 15 mg weekly with a dose increase to 20 mg weekly at week 6 if the Psoriasis Area and Severity Index (PASI) response was < 25%. At week 16, patients with < PASI 50 response could switch treatment groups. The primary efficacy endpoint was PASI 75 response at week 16. Major secondary efficacy endpoints were PASI 75 response at week 26, and the proportion of patients achieving a Physician’s Global Assessment (PGA) score of cleared (0) or minimal (1) at weeks 16 and 26. Others included Dermatology Life Quality Index, 36‐Item Short Form Health Survey, and PGA, PASI 50, PASI 75 and PASI 90 responses over time. Results The primary endpoint was achieved by a significantly greater proportion of infliximab‐treated patients (508/653, 78%) than MTX‐treated patients (90/215, 42%; P < 0·001). Key secondary endpoints also were achieved by a greater proportion of infliximab‐treated patients. Similar responses were observed at week 26 in patients who switched from MTX to infliximab at week 16. Overall adverse event (AE) incidence was comparable between groups, but incidence of serious and severe AEs was slightly higher in the infliximab group. Conclusions Infliximab was well tolerated and more efficacious than MTX in patients with moderate‐to‐severe plaque psoriasis. Infliximab also was efficacious in patients who failed MTX and switched to infliximab.     

Adalimumab treatment for severe recalcitrant chronic plaque psoriasis

Aim.  To assess the efficacy and safety profile of adalimumab in patients with severe, recalcitrant chronic plaque psoriasis, and to assess short-term overlapping of other systemic treatment with adalimumab to prevent flaring of disease.
Methods.  This was a retrospective study comprising 39 patients with chronic plaque psoriasis treated with adalimumab between October 2005 and January 2008. All had failed treatment with other systemic agents, including biological therapies in 59% of patients. Patients were started on adalimumab 40 mg weekly or fortnightly, as clinically indicated. Severity of psoriasis was assessed by the Psoriasis Area and Severity Index (PASI). Therapeutic response was assessed by 75% improvement on PASI (PASI 75). All adverse events were recorded.
Results.  Results were analysed separately for those treated with adalimumab only and those on combination treatment. PASI 75 was achieved in 38% (8 of 21 patients at week 16), 62% (13 of 21 patients) at week 24, 69% (9 of 13 patients) at week 48% and 71% (5 of 7 patients) at week 72 in the adalimumab-only group, compared with 56% (5 of 9 patients) at week 16, 50% (4 of 8 patients) at week 24, 80% (4 of 5 patients) at week 48% and 67% (2 of 3 patients) at week 72 in the combined group. Of the 39 patients, 15 (38%) achieved a PASI of 0 at some point in their treatment. Adalimumab was well tolerated; 38% of patients experienced side-effects, which were generally mild.
Conclusion.  Adalimumab was effective in a group of patients with psoriasis refractory to other systemic therapies, including biological treatments, and was well tolerated.     

Long‐term outcomes of interruption and retreatment vs. continuous therapy with adalimumab for psoriasis: subanalysis of REVEAL and the open‐label extension study

Background REVEAL was a 52‐week study of adalimumab for moderate to severe psoriasis. At Week 33, adalimumab‐treated patients with sustained responses (PASI ≥75 at Weeks 16 and 33) were re‐randomized to receive adalimumab or placebo. Subsequently, they could receive adalimumab in an open‐label extension (OLE) study. Objective To compare long‐term efficacy and safety of adalimumab 40 mg every other week (eow), given as continuous treatment or with one period of interruption followed by retreatment. Methods Patients who were re‐randomized to adalimumab or placebo at REVEAL Week 33 and received ≥1 dose of OLE adalimumab were analysed as the continuous and retreatment groups, respectively, for >2 years of OLE treatment with adalimumab 40 mg eow. LOCF was used for missing efficacy data. Results At OLE Weeks 0, 12 and 24, PASI 75 response rates were 84%, 84%, 86% with continuous treatment (N = 233) vs. 45%, 71%, 79% with retreatment (N = 227). Thereafter, efficacies were slightly greater for continuous treatment but similar between groups, with PASI 75 response rates at OLE Week 108 of 75% vs. 73% respectively. Retreatment was most effective for patients with ≥PASI 50 responses when retreatment was initiated. Adverse event rates for retreatment were equal to or lower than those for continuous treatment. Conclusions In psoriasis patients with sustained PASI 75 responses to adalimumab, long‐term efficacy of retreatment after a ≤19‐week interruption was similar to efficacy achieved with >3 years continuous treatment. Adalimumab retreatment provided the best results when initiated before responses had declined below PASI 50.     

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.     

Adalimumab for psoriasis in Greece: clinical experience in a tertiary referral centre

Background Adalimumab, a fully human, anti‐TNFα monoclonal antibody has been shown to be effective for moderate‐to‐severe psoriasis in clinical trial setting. However, only a limited number of studies reflect everyday clinical experience with this drug. Objectives To provide evidence on the efficacy, dose optimization and safety of adalimumab based on everyday clinical experience in a tertiary referral centre for psoriasis, in Greece. Methods We retrospectively reviewed the records of all patients with moderate‐to‐severe psoriasis who received adalimumab, in our referral centre, between January 2008 and October 2010. Results In total, 52 patients were treated with adalimumab for a mean period of 14 months (range 4–30 months). Mean baseline Psoriasis Area and Severity Index (PASI) was 16.7 (range 9–40.3). At 4, 6, 12 and 18 months, PASI75 was attained by 68%, 82%, 89% and 88% of patients respectively. Nineteen of 52 patients (36%) reached a PASI100 at a mean time of 10 months (range 4–18 months). The dose interval between the injections of adalimumab was increased from 2 to 3 weeks for 14 patients (27%) who achieved and sustained a PASI100 after the first year of treatment, without any relapse. The overall rate of adverse events reached 38%, but treatment was discontinued only in two cases (4%). Conclusions Our study demonstrates that adalimumab is effective and safe in patients with moderate‐to‐severe psoriasis in short‐ and long‐term setting. At the same time, it points out novel and interesting issues for further investigation.     

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.     

An observational,prospective study of monthly adalimumab therapy for disease maintenance in psoriasis patients: a possible new therapeutic option for good responders to the initial induction treatment

Background While adalimumab is a mainstay of treatment for moderate to severe chronic plaque psoriasis, the data regarding optimal treatment intervals for therapeutic maintenance are limited. Objective We compared the clinical efficacy of biweekly maintenance administration of adalimumab with that of monthly treatment. Methods 17 psoriasis patients treated with adalimumab 40 mg every other week with initial loading dose of 80 mg until week 24 were assigned to the maintenance therapy with adalimumab 40 mg either every other week (n = 7), or every month (n = 10). The treatment efficacy was evaluated by the proportion of patients who achieved PASI 75 from the baseline at weeks 36, 48 and 60. There was no selection bias between the two groups. Results At week 24, all the patients except for one in each group achieved PASI 75. In both groups, all the patients who achieved PASI 75 at week 24 maintained PASI 75 responses at week 60. Regarding two patients who did not achieve PASI 75 at week 24, one biweekly treated patient experienced a gradual increase in therapeutic response while one monthly treated patient showed exacerbation after week 24. Conclusion Monthly adalimumab treatment seems to be a reasonable treatment option for patients who responded well to initial standard adalimumab treatment for 24 weeks. Since there are several limitations in this study, including the number of patients, observation period, and patients’ characteristics, large randomized controlled trials are needed to confirm these results.     

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.     

Nail psoriasis: a retrospective study on the effectiveness of systemic treatments (classical and biological therapy)

Background Nail psoriasis represents a challenge for specialists. There is no comparative study of systemic treatment’s effectiveness at this site. Objective: Evaluate the response of nail psoriasis to classical and biological therapy and to compare the effectiveness and safety of the different treatments. Methods We performed a retrospective study of 84 patients with moderate–severe psoriasis seen at our Department between January 2006 and January 2009. Results Psoriasis was severe in 53.4%. In 75% of cases, the fingernails were affected, and the mixed form was the most frequently subtype. The mean baseline scores on the PASI and the NAPSI were 23.12 and 14.7 respectively; the correlation between the two scores fell at weeks 12 and 24 but had risen again at week 48. The baseline NAPSI score tended to be lower in women and significantly higher in patients over 65 years of age, family history of psoriasis, severe psoriasis and nail matrix involvement. In our series, 58.3% received classical treatment (acitretin, methotrexate, cyclosporin, PUVA, NUVB, REPUVA, RENUVB) and 41.7% received biological treatment (infliximab, efalizumab, etanercept, adalimumab).Significant reductions were found (P < 0.05) in the mean NAPSI scores at 12, 24 and 48 weeks with all the antipsoriatic agents except NUVB; significantly greater with cyclosporine (P < 0.01) and biological as infliximab and adalimumab at 12 and 24 weeks (differences between treatments disappeared at 48 weeks). Conclusion The response to treatment is slower in the nail lesions than in the skin lesions. The improvement of nail psoriasis is significant both with the classical treatments significantly higher in cyclosporin; and biological treatment (infliximab and adalimumab at 12 and 24 weeks).     

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.