Treatment Of Chronic Plaque Psoriasis Research Articles

Efficacy and safety of ABT-874, a monoclonal anti–interleukin 12/23 antibody, for the treatment of chronic plaque psoriasis: 36-week observation/retreatment and 60-week open-label extension phases of a randomized phase II trial

ABT-874, an anti-interleukin-12 and -23 antibody, was previously shown to be significantly more effective compared with placebo during a 12-week phase II study of psoriasis. We report here safety and efficacy data of ABT-874 during subsequent phases of this study. We sought to examine the preliminary efficacy and safety of ABT-874 for moderate to severe psoriasis beyond 12 weeks. Patients with chronic plaque psoriasis who responded to ABT-874 during the initial randomized, placebo-controlled, 12-week study phase were eligible for a 36-week observation/retreatment phase. During the subsequent 60-week, open-label extension phase, eligible patients were retreated with one of two ABT-874 dosages. Efficacy was measured using Psoriasis Area and Severity Index and physician global assessment scores; safety was monitored by adverse events (AEs), laboratory parameters, and vital signs. During the observation/retreatment phase, 130 of 180 patients were eligible for retreatment. After 12-week retreatment with ABT-874, 55% to 94% of retreated patients (n= 58) achieved a 75% or greater reduction in Psoriasis Area and Severity Index score. Among patients receiving ABT-874 through the first 48 weeks, there were no deaths and 4 patients with serious AEs; one patient discontinued because of an AE. During the open-label extension (N= 105), there were no deaths or serious infections, and 3 serious AEs. Lack of placebo or active comparator groups limited statistical analysis in later study phases. Dosing differences existed between groups, and only week-12 responders were eligible for retreatment. ABT-874 continued to show good efficacy and safety during withdrawal and reinitiation of therapy.

Efficacy and safety of mycophenolate mofetil vs. methotrexate for the treatment of chronic plaque psoriasis

Methotrexate (MTX) is a well-known systemic drug for moderate to severe chronic plaque psoriasis. Recently, mycophenolate mofetil (MMF) has been recommended for psoriasis. To compare the efficacy and safety of MMF vs. MTX for the treatment of chronic plaque psoriasis. Thirty-eight consecutive patients with Psoriasis Area and Severity Index (PASI)>10 were randomly assigned for 12 weeks of treatment with either MTX (18 patients; initial dose, 7.5 mg/week) or MMF (20 patients; dose; 2 g/day) and were followed for 12 weeks after discontinuing the treatment. The differences between the two groups were analysed at the end of treatment and follow-up comparing with baseline values. After 12 weeks of treatment, the mean ± SD score for the PASI decreased from 16.46 ± 5.29 at baseline to 3.17 ± 2.35 among 15 patients treated with MTX, whereas the score decreased from 17.43 ± 7.42 to 3.97 ± 5.95 among 17 patients treated with MMF (P>0.05). Twelve weeks after discontinuing the treatment, the scores were 4.77 ± 3.52 and 5.94 ± 4.27, respectively (P>0.05). PASI -75 were achieved in 58.8% of patients in MMF group and 73.3% in MTX group (P > 0.05). Three months after discontinuing the treatment, PASI-75 remained in 33.3% of patients in MMF and 53.3% of MTX group (P > 0.05). Both drugs were well tolerated and side-effects were minor and transient. No significant differences in efficacy were found between MTX and MMF groups. MMF may represent a good alternative for the treatment of psoriasis in patients who are unable to take MTX or other available drugs due to contraindication or toxicity.

Clinical and genetic predictors of response to narrowband ultraviolet B for the treatment of chronic plaque psoriasis

There is considerable variability in the number of exposures of narrowband ultraviolet B (NB-UVB) needed to clear psoriasis and in the duration of remission. We assessed clinical parameters as predictors of the number of exposures needed to clear psoriasis and of the duration of remission. The influence of genetic polymorphisms of the vitamin D receptor (VDR) on treatment response was also evaluated. This was a prospective study of 119 patients with chronic plaque psoriasis treated with NB-UVB until clearance was achieved. They were then followed for up to 1 year or until relapse occurred. The frequency of the Fok1, Apa1, Bsm1, Taq1 and rs4516035 polymorphisms of the VDR gene was assessed in 93 of the 119 patients. Of the 119 patients, 105 completed the course of phototherapy. Using an intention to treat analysis, 83% of the initial cohort (99 of 119 patients) achieved clearance, in a median of 26 exposures (interquartile range 19-35) with a median remission duration of 16 weeks (interquartile range 9-22). Factors significantly associated with a lower number of exposures to clearance included a lower baseline Psoriasis Area and Severity Index (P = 0·004), lower baseline Dermatology Life Quality Index (P = 0·047), female sex (P = 0·043), lower body weight (P = 0·008), and a higher number of previous courses of TL-01 (P = 0·005). The only clinical factor influencing remission duration was number of exposures (P = 0·0009), with a decreased remission duration in those who required a greater number of exposures to clear. The Taq1 VDR polymorphism (rs731236) also significantly predicted remission duration (P = 0·038). Patients homozygous for the C allele, which is associated with decreased activity of the VDR, had a shorter remission duration than those heterozygous for the allele (P = 0·026) and those homozygous for the T allele (P = 0·013). This study highlights the fact that both genetic and clinical parameters are important in determining treatment outcomes in psoriasis.

Improving clinical trial design in psoriasis: Perspectives from the global dermatology community

Background: Clinical trials to test investigational drugs for the treatment of chronic plaque psoriasis currently lack standards for comparison of efficacy and safety data.The majority of studies do not address the important need for long-term treatment. Methods: The International Psoriasis Council (IPC) conducted two surveys of its members to assess the need for gold standards, active comparators, and long-term therapy in clinical trials. In Survey 1, 30 participants delivered viewpoints on active comparators for topical therapy (six questions), systemic therapy (nine questions), and continuous versus intermittent therapy (six questions). In Survey 2, 31 participants provided input on gold standards for treatment (five questions), appropriate comparators (four questions), and continuous versus intermittent therapy (six questions). The IPC leadership interpreted the results after each survey. Results: The majority of participants (77% in Survey 1 and 89% in Survey 2) agreed that studies of investigative treatments should include an active comparator. Participants described the most important feature of a gold standard as a treatment that: is widely used and generally accepted (45%); has the best efficacy (42%); and is well tolerated (13%). The majority agreed that gold standards should be dependent on: patient subgroup; location/extent of psoriasis; and psoriasis subtype/morphology. It was also agreed that continuous therapy for more than 3 years is needed for patients with moderate-to-severe plaque psoriasis. We have provided an expert opinion regarding the definition of a gold standard in psoriasis and have also established that no single treatment can be the gold standard across all subgroups and types of the disease. Conclusions: A single gold standard for the treatment of psoriasis does not exist. The complexity and heterogeneity of psoriasis requires different gold standards for the various manifestations of psoriasis and for subgroups of patients reconciling comorbidities. Of note, 17 experts out of 30 selected methotrexate as the most nominated gold standard amongst systemic agents. The experts support the election of an active comparator as one that is most efficacious over just the best in a particular class. In concordance, 87% of respondents agreed that good tolerability is therefore not the lead criterion for selection of an active comparator in favor of effectiveness and broad use. Patients with moderate-to-severe plaque psoriasis require continuous therapy; this statement was supported by 93% of the experts. Reasons for considering long-term therapy included appearance of comorbidities, impairment of quality of life, possibility of relapse, and subjective complaints such as itch, pain, and joint disease.

Development of monoclonal gammopathy in 12 patients receiving efalizumab treatment for chronic plaque psoriasis

Development of monoclonal gammopathy in 12 patients receiving efalizumab treatment for chronic plaque psoriasis

Potential role of ustekinumab in the treatment of chronic plaque psoriasis.

Psoriasis is a relatively common, chronic and disabling skin disease, with an immune-related pathogenesis and a genetic background which may be triggered by several environmental factors including smoking and infections. There is no cure but several treatment options are available. The treatment of psoriasis is far from being satisfactory due to impractical modalities of topical treatment and suboptimal safety profile of the systemic treatments available. In the last few years, parallel to an improved understanding of the disease pathogenesis, there has been a boost in research on new agents for the treatment of psoriasis. Ustekinumab, a monoclonal antibody targeting the p40 subunit of interleukin (IL)-12 and IL-23, is one such new agent. Psoriasis and its management are briefly reviewed before focusing on the evidence for ustekinumab in the treatment of chronic plaque psoriasis through a systematic search of the main registries of ongoing trials up to December 2009. Ustekinumab proved to be very effective short term in the control of clinical manifestations in psoriasis compared with placebo and with etanercept. Long-term and comparative data are still limited. There is a need for continuing research on the long-term effectiveness and safety of the drug.

The safety profile and sustained remission associated with response to multiple courses of intramuscular alefacept for treatment of chronic plaque psoriasis

Safety and efficacy of up to 3 courses of alefacept intramuscular (IM) in the treatment of chronic plaque psoriasis have been demonstrated in earlier trials. We sought to determine the safety and efficacy of up to 5 courses of alefacept IM in treating plaque psoriasis. A standard treatment course was defined as 15 mg of alefacept IM once weekly for 12 weeks, followed by 12 weeks of treatment-free observation. Patients with chronic plaque psoriasis, who had previously received alefacept IM, received up to 3 additional courses (A, B, and C). Efficacy was evaluated by Physician Global Assessment. Safety profiles were similar to those for a single course of treatment. There were no cumulative adverse effects. At 2 weeks postdosing, 16%, 22%, and 19% of patients were rated clear or almost clear by Physician Global Assessment in courses A, B, and C, respectively, with 35%, 42%, and 42% achieving this response at any time during these courses. Patients who achieved clear or almost clear at 2 weeks postdosing remained so for a median duration of 214 and 126 days after courses A and B, respectively. This was an extension study and therefore contained no control group. Up to 5 courses of alefacept IM may provide extended treatment-free, symptom-free periods in responders while maintaining the safety profile.

Methotrexate/narrowband UVB phototherapy combination vs. narrowband UVB phototherapy in the treatment of chronic plaque‐type psoriasis – a randomized single‐blinded placebo‐controlled study

Psoriasis is a chronic, recurring inflammatory disease affecting the skin, joints and nails that has a significant negative impact on the quality of life. Efficacy of combination of methotrexate/narrowband ultraviolet B (NBUVB) phototherapy in the treatment of psoriasis has been rarely assessed. To compare the efficacy of methotrexate/NBUVB phototherapy combination vs. NBUVB phototherapy in the treatment of chronic plaque psoriasis. Forty patients with chronic plaque-type psoriasis (body surface area involvement >10%) were randomized to receive either methotrexate/NBUVB phototherapy (group A) or placebo/NBUVB phototherapy (group B). End point of treatment was 75% reduction in Psoriasis Area and Severity Index (PASI) Score or upto 6 months, whichever was earlier. Patients were then followed up for a period of 12 weeks for assessment of relapse. Of 40 patients, 37 completed the treatment period and 29 both the treatment period and follow-up. PASI 75 was achieved in 19/20 patients in group A and 14/20 patients in group B (P < 0.04). The mean number of weeks(P = 0.001), the mean cumulative dose of NBUVB (P = 0.001) and the mean number of phototherapy sessions (P = 0.0001) required to achieve PASI 75 were significantly less in group A compared with group B. There was no significant difference in the number of patients who relapsed during the follow-up period (P = 0.68). Combination of methotrexate and NBUVB phototherapy provides more rapid clinical improvement compared with NBUVB monotherapy in the treatment for chronic plaque-type psoriasis.

A comparison of three times vs. five times weekly narrowband ultraviolet B phototherapy for the treatment of chronic plaque psoriasis

Narrowband ultraviolet B (NB-UVB) phototherapy is an effective treatment for psoriasis. To compare the effects of three and five times weekly NB-UVB phototherapy in the treatment of chronic plaque psoriasis. Sixty-five patients with chronic plaque psoriasis were allocated to receive three or five times weekly NB-UVB, starting at low dose. Among the patients who completed the study, clearance was achieved in 18 out of 23 patients (78%) in the three times weekly group and in 15 out of 22 patients (68%) in the five times weekly group. The difference was not statistically significant (P=0.44). No statistically significant differences were found between the two groups in the number of treatments (P=0.95), cumulative UVB dose (P=0.51), and rate of side-effects. Length of the treatment period was significantly shorter in the five times weekly group (P<0.001). At the end of treatment, the mean psoriasis area and severity index score was lower in the three times weekly group (P=0.02). We recommend three times weekly NB-UVB for chronic plaque psoriasis; however, the more rapid clearance of psoriasis with five times weekly phototherapy may justify using this method in some patients.

Cost-effectiveness analysis of TNF-α blockers for the treatment of chronic plaque psoriasis in the perspective of the Italian health-care system

The cost-effectiveness of biological treatments for psoriasis is not well determined and may vary from country to country. The objectives of this study was to perform a cost-effectiveness analysis of infliximab compared with other anti-tumor necrosis factor-alpha agents for the treatment of psoriasis in Italy. The incremental cost-effectiveness ratio per patients achieving at least 75% improvement in the psoriasis area and severity index assessed over 24- and 48-50-week periods was calculated. Efficacy data were drawn from randomized controlled trials when available or from open label studies. Considering patients achieving psoriasis area and severity index at week 24 and 48-50, infliximab was dominant (more effective and less costly) over etanercept given at 50 mg twice weekly. In contrast, infliximab was not dominant over etanercept at other dosages or over adalimumab. When considering the impact of therapy on quality of life at Week 12 using the Dermatology Life Quality Index equal to zero, infliximab resulted more effective and less costly than etanercept. Therefore, infliximab seems to be cost-effective in the therapy of psoriasis. Further cost-efficacy evaluations based on head-to-head trials are necessary to address health economic considerations.

Clinical Experience with Alefacept in Canadian Patients with Psoriasis: The Amevive Wisdom Acquired from Real-world Evidence (AWARE) Study

Background Alefacept was the first biologic therapy approved for the treatment of chronic plaque psoriasis in Canada. Objective The AWARE study was an observational phase IV study whose main goal was to describe the outcomes of alefacept treatment in a broad population of Canadian psoriasis patients. Methods A total of 426 patients with chronic plaque psoriasis were enrolled from 37 clinics across Canada. Patients were treated with up to two courses of alefacept and followed for up to 60 weeks. Results The majority of patients had a moderate to marked response to alefacept treatment. Treatment with concomitant systemic therapy was discontinued or reduced in up to a third of subjects. Forty percent completed the entire follow-up period without receiving a second course of alefacept. Conclusion In routine clinical settings in Canada, alefacept is an effective and safe option for the treatment of a wide range of patients with psoriasis.

Randomized, double-blind, placebo-controlled evaluation of the efficacy of oral psoralen plus ultraviolet A for the treatment of plaque-type psoriasis using the Psoriasis Area Severity Index score (improvement of 75% or greater) at 12 weeks

Psoralen plus ultraviolet A (PUVA) for the treatment of psoriasis has never been evaluated using the Psoriasis Area Severity Index (PASI) in a randomized, double-blind, placebo-controlled trial. The lack of such data limits our capacity to estimate PUVA's efficacy relative to other treatment options that are available today. The purpose of this study was to evaluate the efficacy of PUVA therapy for patients with plaque-type psoriasis. This study involved 40 patients with psoriasis; 30 received PUVA and 10 received UVA with placebo. PASI scores were assessed at baseline and every 4 weeks thereafter for 12 weeks. By nonresponder imputation, 60% (18 of 30) in the PUVA group achieved 75% or more improvement in PASI score after 12 weeks of treatment compared with 0% (0 of 10) in the UVA plus placebo group (P < .0001). Using intent to treat with last observation carried forward analysis, 63% (19 of 30) in the PUVA group achieved 75% or more improvement in PASI score compared with 0% (0 of 10) in the UVA plus placebo group (P < .0001). By per protocol analysis, 86% (18 of 21) in the PUVA group as compared with 0% (0 of 7) in the UVA plus placebo group reached 75% or more improvement in PASI score after 12 weeks (P < .0001). The study was relatively small with only 40 patients enrolled and 28 patients who completed the protocol. Further studies that involve head-to-head comparison of PUVA with other treatment modalities are needed. Nonresponder imputation, last observation carried forward with intent to treat, and per protocol analyses each have separate advantages and limitations when determining clinical significance. This study supports the observation that PUVA is a highly efficacious treatment for chronic plaque psoriasis.

Novel topical therapy for mild-to-moderate plaque psoriasis: focus on calcitriol.

The benefits of vitamin D derivatives for the treatment of chronic plaque psoriasis are well documented. Of importance is how compatible they are with, and how they compare to, other established treatments for psoriasis. This paper reviews 15 studies with calcitriol 3 μg g(-1) ointment (Silkis(®)/Vectical(™) ointment; Galderma Laboratories) applied twice daily for up to 52 weeks. The ointment was found to be effective and safe for the treatment of mild-to-moderate plaque psoriasis including sensitive skin areas. Calcitriol 3 μg g(-1) ointment was found to be as effective as, or even superior to, other established treatment modalities and more highly tolerated than other local treatment modalities in most studies' comparisons. It could be combined with other psoriasis treatment modalities such as ultraviolet B phototherapy or topical corticosteroids in order to achieve a faster response and in order to reduce the risk of adverse events.

Biologics in the Treatment of Psoriasis: Clinical and Economic Overview

The use of biologic medications for psoriasis is a recent therapeutic advance. To review clinical and economic data for biologic therapies in the treatment of chronic plaque psoriasis. Published meta-analyses and additional literature review identified randomized controlled trials. Analyses included the number needed to treat (NNT), the cost in Canadian dollars for the first year of treatment per the Canadian product monograph, and the estimated cost per responder achieving a 75% reduction in Psoriasis Area and Severity Index score (PASI 75). Pooled NNTs were 1.3 (infliximab), 1.5 (ustekinumab 90 mg), 1.6 (adalimumab and ustekinumab 45 mg), 2.3 (etanercept), 4.1 (efalizumab), and 5.6 (alefacept). The annual treatment cost per patient was $19,825 to $37,600. The cost per patient achieving a PASI 75 response at 12 weeks ranged from $8,330 (adalimumab) to $71,371 (alefacept). This analysis suggests favorable cost and benefits of biologic psoriasis therapies, particularly adalimumab, infliximab, and ustekinumab.

Treatment of severe, recalcitrant, chronic plaque psoriasis with fumaric acid esters: a prospective study

Fumaric acid esters (FAE) are used in Germany as a first-line systemic treatment for chronic plaque psoriasis, with proven efficacy and low toxicity. Their use in the U.K. is variable, and they remain unlicensed. Consequently, efficacy and safety data from U.K. patients is limited and their place in the psoriasis treatment armamentarium is unclear. To examine the efficacy and safety of FAE in a prospective cohort of U.K. patients with severe, treatment-recalcitrant, chronic plaque psoriasis. A single-centre, open, nonrandomized, prospective study was performed in a regional referral centre for patients with severe psoriasis. Outcomes were measured by the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), blood investigations and adverse events monitoring. Eighty patients were recruited. Fifty-nine per cent were taking a concomitant oral antipsoriatic agent; 20% achieved a PASI-50, 8% a PASI-75 and 4% a PASI-90 on intention-to-treat analysis at 3 months with an overall, statistically significant, reduction in PASI from 13.9 + or - 9.0 to 11.3 + or - 9.2 (P < 0.0001). At 3 months, lymphopenia was seen in 33% of the cohort with significantly lower counts in patients responsive to FAE (P = 0.008). In addition, by 3 months, 36% of concomitant antipsoriatic medication had been stopped and 25% of doses had been reduced without loss of disease control. Side-effects (most commonly diarrhoea, abdominal pain and flushing) were reported by 74% of patients resulting in cessation of FAE in 36%. FAE is a useful alternative treatment option in patients with severe, treatment-resistant, chronic plaque psoriasis and can allow dose reduction, and subsequent cessation, of other, potentially more toxic agents.

An Open-Label Trial of Thalidomide in the Treatment of Chronic Plaque Psoriasis

Background Thalidomide inhibits tumor necrosis factor (TNF)-α. Purpose To assess the effectiveness of thalidomide in the treatment of psoriasis. Methods Twenty subjects with moderate to severe psoriasis were treated with 200 mg of thalidomide daily. Clinical response was observed for 16 weeks with the last dose of thalidomide at 12 weeks. Results The severity of psoriasis improved as measured by both psoriasis area and severity index (PASI) and body surface area (BSA) with 40% having &gt;50% improvement by 16 weeks. Mean PASI improvement at weeks 12 and 16 was 32% and 48%, respectively. Lower extremity edema developed in three of the first six patients enrolled, and the starting dose was amended from 200 mg/day to 100 mg/day. Limitations The open-label study design and concomitant therapy, albeit inadequately effective, complicates interpretation. Conclusion Thalidomide was effective and moderately well-tolerated in patients with psoriasis.

Adalimumab vs Methotrexate for the Treatment of Chronic Plaque Psoriasis

Jonathan M. Batchelor, BMedSci, BM BS, MRCP(UK); John R. Ingram, DM, MRCP(UK); Hywel Williams, MSc, PhD, FRCP; Department of Dermatology, Addenbrooke’s Hospital, Cambridge, England (Dr Batchelor); Department of Dermatology, University Hospital of Wales, Heath Park, Cardiff (Dr Ingram); Centre of Evidence-Based Dermatology, University of Nottingham, King’s Meadow Campus, Nottingham, England (Dr Williams)

Long-term safety and efficacy of efalizumab in the treatment of chronic plaque psoriasis: Interim data from the Canadian RESTORE study

Long-term safety and efficacy of efalizumab in the treatment of chronic plaque psoriasis: Interim data from the Canadian RESTORE study

Imaging of Effector Memory T Cells during a Delayed-Type Hypersensitivity Reaction and Suppression by Kv1.3 Channel Block

Effector memory T (Tem) cells are essential mediators of autoimmune disease and delayed-type hypersensitivity (DTH), a convenient model for two-photon imaging of Tem cell participation in an inflammatory response. Shortly (3 hr) after entry into antigen-primed ear tissue, Tem cells stably attached to antigen-bearing antigen-presenting cells (APCs). After 24 hr, enlarged Tem cells were highly motile along collagen fibers and continued to migrate rapidly for 18 hr. Tem cells rely on voltage-gated Kv1.3 potassium channels to regulate calcium signaling. ShK-186, a specific Kv1.3 blocker, inhibited DTH and suppressed Tem cell enlargement and motility in inflamed tissue but had no effect on homing to or motility in lymph nodes of naive and central memory T (Tcm) cells. ShK-186 effectively treated disease in a rat model of multiple sclerosis. These results demonstrate a requirement for Kv1.3 channels in Tem cells during an inflammatory immune response in peripheral tissues. Targeting Kv1.3 allows for effector memory responses to be suppressed while central memory responses remain intact.

Economic evaluation of etanercept in the management of chronic plaque psoriasis

The National Institute for Health and Clinical Excellence has recommended that etanercept 25 mg twice weekly (biw) be used in adults with severe plaque psoriasis. However, its economic model did not consider the alternative licensed regimen of etanercept 50 mg biw. To assess the cost-effectiveness of etanercept 50 mg biw for the treatment of chronic plaque psoriasis, and to explore characteristics of patients who benefited most from 50 mg dosing. An economic model was constructed to estimate the incremental cost per quality-adjusted life year (QALY) gained. The model considered patients with chronic plaque psoriasis who had both Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) of 10 or higher who were unable to take standard systemic therapies. Quality of life gain was estimated from the DLQI responses of patients enrolled in three clinical studies. The model considered expenditure on drugs, monitoring visits, adverse events and inpatient stays. Costs were estimated from the perspective of the U.K. National Health Service over a time period of 10 years. The incremental cost per QALY for etanercept 50 mg biw compared with no systemic therapy was found to be 6217 pounds sterling (95% confidence interval 5396-7486 pounds sterling). The cost-effectiveness of 50 mg dosing was more attractive in patients with baseline PASI > or = 20 (5163 pounds sterling) or baseline DLQI > or = 20 (4599 pounds sterling). This model found the licensed dose regimen of etanercept 50 mg biw to be cost effective in the U.K. This regimen was particularly appropriate for patients with severe disease or poor quality of life at baseline.