Courses Of Alefacept Research Articles

Immune response to pneumococcal polysaccharide vaccine in adults with chronic plaque psoriasis treated with alefacept

Alefacept is a T cell-modulating biologic therapy for psoriasis that could affect patients' ability to mount immune responses. This open-label, phase IV, multicenter study assessed the ability of adults with chronic plaque psoriasis receiving alefacept to generate antibodies to a pneumococcal polysaccharide vaccine (PPV). Patients were treated with a standard 12-week course of alefacept and administered the 23-valent PPV at week 6. Antipneumococcal antibodies were measured at baseline and weeks 6, 9, 12, and 33. The primary end point was the percentage of patients with a 2-fold or greater increase from prevaccination (week 6) to 6 weeks postvaccination (week 12) in antibody titers to 2 or more of 5 designated PPV antigens. Of 43 patients enrolled, 42 were included in the full analysis set, with 86% of patients exhibiting a 2-fold or greater increase and 57% of patients exhibiting a 4-fold or greater increase in antibody titers to 2 or more of 5 designated antigens from prevaccination to 6 weeks postvaccination. At 6 months postvaccination, 78% of patients had a 2-fold or greater increase and 47% of patients had a 4-fold or greater increase in antibody titers to 2 or more of the 5 designated antigens. There were statistically significant increases in mean antibody titers to all 23 antigens in PPV from prevaccination to 6 weeks postvaccination. This was an open-label study with no comparator. Most patients mounted immune responses to PPV; increases in antibody titers in these patients were consistent with those seen in healthy individuals.

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.

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.

Efficacy Outcomes in Patients Using Alefacept in the AWARE Study

Alefacept has demonstrated efficacy in clinical trials of patients with chronic plaque psoriasis, either as monotherapy or combined with other treatment modalities such as phototherapy. AWARE (Amevive Wisdom Acquired from Real-World Evidence) is a multicenter, observational, phase IV Canadian registry of psoriasis patients treated with alefacept. Patients with chronic plaque psoriasis were treated with at least one course of alefacept, either alone or added on to their existing antipsoriatic treatment regimen. Each course of alefacept was followed by a period of at least 12 weeks off treatment. Efficacy outcomes included physicians' and patients' assessments of response at week 18, as well as change in percent body surface area (BSA) involvement with psoriasis. The time to retreatment was assessed in patients receiving a second course of alefacept during at least 60 weeks of prospective follow-up. The majority of patients received alefacept in combination with other antipsoriatic therapies. Physicians' and patients' assessments of response at 18 weeks showed that 42% and 41% of patients, respectively, had a "cleared to marked response" and a further 42% had a "moderate to some response." Among those patients whose psoriasis was moderately controlled or not controlled at baseline, 49 to 51% and 33 to 36%, respectively, improved to "cleared to marked response" at 18 weeks. A substantial shift in percent BSA involvement with psoriasis was observed at 18 weeks, with 55% of patients having a BSA involvement of < 10% at week 18 compared to only 20% having this level of BSA involvement at baseline. The mean time to retreatment among the 60% of patients who received a second course of alefacept was 19.3 weeks (range 2-47 weeks). A single course of alefacept therapy improved outcomes in this broad population of real-world chronic plaque psoriasis patients. The limitations of this study include its nonrandomized, noncontrolled, noncomparative design, which allowed multiple different treatment approaches across all patients. The rating scales used in this study have not been previously validated, and ranges were assigned to baseline control and response data that are not specifically defined. Clinicians did not receive specific training in using these scales; therefore, interrater variability could not be assessed.

Update on Alefacept Safety

Alefacept has been demonstrated in clinical trials to be an effective, safe, and well-tolerated treatment strategy when used alone or in combination with other antipsoriatic therapies in patients with chronic plaque psoriasis. AWARE (Amevive Wisdom Acquired from Real-World Evidence) is a multicenter, observational, Canadian phase IV registry evaluating the efficacy and safety of alefacept, alone or in combination with other antipsoriatic therapies, in patients with psoriasis. Patients with chronic plaque psoriasis were treated with at least one course of alefacept followed by an off-treatment period, typically lasting 12 or more weeks. Prospective follow-up was at least 60 weeks, depending on when patients presented for retreatment. Safety data collected throughout the study included the incidence of serious adverse events (SAEs), dosing suspensions, and withdrawals owing to adverse events. Twelve SAEs were reported in psoriasis patients treated with at least one course of alefacept, with only one considered to be possibly related to the study drug. Approximately one-quarter of patients missed at least one dose of alefacept during the course of the study. A total of 291 doses of alefacept were missed, representing almost 4% of the total doses administered in this group of patients. Low CD4(+) count was the most frequent reason for missed doses; however, no patient had persistently low CD4(+) counts requiring permanent discontinuation of alefacept treatment. Seven patients in the AWARE registry discontinued treatment with alefacept, with the most common reason being patient request. The AWARE study supports the safety of alefacept used alone or in combination with other antipsoriatic therapies, in a broad population of real-world chronic plaque psoriasis patients in Canada.

Alefacept with methotrexate for treatment of psoriatic arthritis: Open-label extension of a randomized, double-blind, placebo-controlled study

A single course of alefacept intramuscularly in combination with methotrexate (MTX) was effective in treating both psoriasis and psoriatic arthritis (PsA). We sought to determine the efficacy and safety of an additional course of alefacept intramuscularly in combination with MTX in patients with PsA. In this open-label extension study, patients with PsA on stable doses of MTX were treated with an additional 12 weekly intramuscular injections of alefacept followed by 12 weeks of observation. Efficacy of PsA treatment was measured as 20% reduction in American College of Rheumatology criteria (ACR20). At the end of the open-label extension phase, 86 of 160 (54%) patients achieved ACR20, of which 28 of 55 had received placebo plus MTX and 58 of 105 received alefacept plus MTX in the prior double-blind phase. Although there was no increase in the proportion of patients achieving ACR20 after a second course of alefacept plus MTX, those achieving ACR50 and ACR70 increased from 17% and 7%, respectively, in the double-blind phase to 32% and 12%, respectively, in the open-label extension phase. In this open-label extension phase of the study there was no control group and the effect on psoriasis in these patients was not measured. Patients with psoriasis and PsA on stable doses of MTX derive benefit for both conditions from one or more courses of alefacept, with further benefit in PsA apparent after a second course of treatment. No additional toxicity was observed.

Alefacept in the treatment of psoriasis

Alefacept is the first biologic agent approved by the US Food and Drug Administration for the treatment of psoriasis. To date, more than 1000 patients with moderate to severe psoriasis have been enrolled in phase III clinical trials of alefacept. More than 30% of patients treated with 2 courses of alefacept reached a Physician's Global Assessment of clear to almost clear, and approximately 40% and 70% of patients achieved a Psoriasis Area Severity Index score of 75 and 50 after the same regimen. Alefacept is well tolerated, and there have been no reports of significant systemic toxicity or serious treatment-related adverse events.

Alefacept for moderate to severe atopic dermatitis: A pilot study in adults

Atopic dermatitis is a common inflammatory skin condition with acute and chronic phases showing a prevalence of memory T cells. Alefacept is a fully human LFA-3/IgG1 fusion protein that inhibits T-cell activation and selectively reduces memory T cells, which may prove to be effective in the treatment of atopic dermatitis. We sought to evaluate clinical response of alefacept intramuscular (IM) injection for 16 weeks in adults with atopic dermatitis. This was an open-label study of a 16-week treatment regimen of alefacept IM injection in adults with moderate to severe inflammatory atopic dermatitis. Patients received alefacept (30 mg IM) weekly for the first 8 weeks. At week 9, patients who did not achieve a 50% reduction in their Eczema Area Severity Index (EASI) score continued on alefacept (30 mg IM) weekly; those patients with a 50% reduction in their EASI (EASI 50) score or higher had their weekly dose decreased (15 mg IM) for the remaining 8 weeks. Nine patients with moderate to severe atopic dermatitis were enrolled and treated. At the primary end point, week 18, 1 patient achieved EASI 50 score and 1 patient achieved EASI 90 score; 4 patients had a decrease in EASI score of less than 50%, 1 patient had an increase in EASI score, and 2 patients withdrew early before the primary end point because of worsening disease. A Physician Global Assessment score of mild was achieved in 2 patients and 1 patient achieved a Physician Global Assessment score of almost clear. Minimal pruritus was reported by 3 patients and 1 patient reported no pruritus. The 16-week course of alefacept was well tolerated. The study was inherently limited by its small sample size, concomitant use of antihistamines, and open-label design, which increases the likelihood of observer and self-assessment bias. The treatment regimen of alefacept for 16 weeks was well tolerated by our patients. Although, in this study, only 2 of the 9 patients with atopic dermatitis responded to treatment with alefacept, the study was inherently limited by the small sample size. Additional studies with a larger sample size, continued weekly use, or concomitant use of ultraviolet-B light therapy may be warranted to evaluate the possibility of alefacept as a therapy for patients with chronic atopic dermatitis.

The Safety and Efficacy of High‐Dose Alefacept Compared With a Loading Dose of Alefacept in Patients With Chronic Plaque Psoriasis

Alefacept is a biologic response modifier indicated for moderate to severe psoriasis; it has been available since 2003. It is typically administered in a dosing regimen of 15 mg intramuscularly (IM) weekly for 12 weeks. The purpose of this study was to determine whether a higher dose may be more beneficial in achieving a 75% reduction in the Psoriasis Area and Severity Index (PASI 75). A secondary objective of this study was to examine whether increasing the dose during the initial course of alefacept would reduce the time to onset of efficacy and overall response rate. Two separate dosing regimens are evaluated in this study: 30 mg IM for 6 weeks followed by 15 mg IM for 6 weeks (group 1) and alefacept 30 mg IM weekly for 12 weeks (group 2). Efficacy was assessed using the PASI, Physician Global Assessment, body surface area, and photographic evaluation of a target lesion. A total of 20 patients enrolled and were randomized, 16 of whom completed the study. Data analyses were performed on a per-protocol basis. Overall, the mean PASI scores progressively decreased, with 43.8% reaching a 50% reduction in the PASI (PASI 50) at week 14 evaluation. Of these participants, 37.5% were in group 1 and 50% were treated with alefacept 30 mg IM for 12 weeks (group 2). Although our sample size was small, 12.5% of patients (one patient in each treatment arm) reached PASI 75. The most common adverse events encountered in this trial were mild infection, headache, pruritus, and erythroderma. There were no infections associated with a CD4(+) cell count <250 cells/mm(3). There was no difference between the treatment groups in achieving PASI 50 or PASI 75. In addition, in our small population, the higher doses of alefacept were associated with increased adverse effects, including erythroderma.

Safety and efficacy of an extended course of alefacept of up to 12 additional weekly doses following a standard 12-week course of alefacept

Safety and efficacy of an extended course of alefacept of up to 12 additional weekly doses following a standard 12-week course of alefacept

Use of extended courses of alefacept in the treatment of moderate to severe psoriasis

Use of extended courses of alefacept in the treatment of moderate to severe psoriasis

Sustained long-term remission of chronic plaque psoriasis upon treatment with multiple courses of alefacept

Sustained long-term remission of chronic plaque psoriasis upon treatment with multiple courses of alefacept

A multicenter, open‐label study of repeat courses of intramuscular alefacept in combination with other psoriasis therapies in patients with chronic plaque psoriasis

Objective: To evaluate the safety and efficacy of multiple courses of alefacept in combination with traditional psoriasis therapy for the treatment of chronic plaque psoriasis (CPP). Methods: Patients with CPP requiring systemic therapy were eligible for this study. Patients received up to three courses of intramuscular alefacept 15 mg once weekly for 12 weeks. One concomitant psoriasis therapy (topical agents, methotrexate, cyclosporine, systemic retinoids, or ultraviolet B [UVB]) per course was allowed. The extent of disease was determined using the 7‐point Physician Global Assessment (PGA; scale ranging from 0 = clear to 6 = severe). Results: More than 73% of patients improved by ⩾ one PGA category and ⩾44% of patients improved by ⩾ two PGA categories across all concomitant treatments. Clinical responses tended to be greatest in patients who received alefacept plus UVB. The incidences of serious infections (⩽1%) and malignancies (⩽2%) were low across all courses and all combinations. Conclusion: Multiple courses of alefacept appear to be well tolerated and demonstrate efficacy in patients with CPP when administered with other psoriasis therapies.

Alefacept revisited: Our 3-year clinical experience in 200 patients with chronic plaque psoriasis

Alefacept was the first biologic agent approved in the United States for the treatment of moderate to severe chronic plaque psoriasis (January 2003). Standard prescription is 12 weekly intramuscular doses. The mechanism of action involves the inhibition of T-cell activation and the selective induction of apoptosis of memory T cells. A proportion of patients responding to therapy have been reported to experience remissions of approximately 7 to 8 months, characterized by disease-free and treatment-free intervals. We sought to evaluate the efficacy and safety of alefacept treatment in patients with psoriasis during routine clinical practice. We conducted a retrospective chart analysis of data involving 201 patients and 296 courses of alefacept from February 2003 to January 2006. Standard informed consent was obtained. Of the 62 patients (32.6%) who achieved an excellent response, 45% received dosage regimens defined as alternative and 73% had concomitant therapy in at least one of the treatment courses that they received. The average remission time of these patients who achieved an excellent response was approximately 7 months, with a maximum of up to 25 months. Adverse events were generally manageable and rarely led to treatment discontinuation. Study data rely on retrospective analysis of chart-documented clinical examination findings, and patient compliance with visit schedules. Alefacept is a long-term treatment option for psoriasis with long-term remissions noted in a proportion of patients.

Open-Label, Single-Center, Safety Dose Escalation Trial of Alefacept for the Treatment of Moderate to Severe Chronic Plaque Psoriasis

Alefacept (Amevive) is a fully human LFA-3/IgG1 fusion protein with a dual mechanism of action inhibiting T-cell activation and selectively reducing memory T cells. Alefacept is currently approved as a 12-week course of weekly 15 mg intramuscular (IM) injections for the treatment of adults with moderate to severe chronic plaque psoriasis. In clinical trials using the currently approved dosing regimen, 33% and 57% of patients achieved a 75% or greater or 50% or greater reduction in Psoriasis Area and Severity Index score (PASI 75 and PASI 50), respectively, after one course of alefacept. To evaluate the tolerability and efficacy of alefacept 15 mg IM weekly for 6 weeks followed by alefacept 30 mg IM weekly for 6 weeks. Open-label, single-center, dose escalation study of alefacept. Adult patients with chronic plaque psoriasis involving a minimum body surface area of 10% and with a minimum PASI of 12. Patients were treated with alefacept 15 mg IM for 6 weeks followed by alefacept 30 mg IM for an additional 6 weeks; doses were held for CD4 counts < 200 cells/mm(3) or evidence of a clinically significant infection. Efficacy was evaluated by PASI and Physician Global Assessment (PGA) at baseline, week 7, and 2, 6, 12, and 24 weeks post-treatment. Sixteen patients were enrolled; at 6 weeks post-treatment, the PASI mean reduction was 39%, with continued improvement to 46% at 12 weeks post-treatment. The PASI 90, PASI 75, and PASI 50 responses at 12 weeks post-treatment were 6% (1 of 16), 13% (2 of 16), and 38% (6 of 16), respectively; 12% (2 of 16) of patients achieved a PGA of clear to almost clear at 12 weeks post-treatment. The overall PASI 75 and PASI 50 responses were 19% (3 of 16) and 38% (6 of 16), respectively. The treatment regimen of alefacept 15 mg IM for 6 weeks followed by alefacept 30 mg IM for 6 weeks was well tolerated by our patients. There was no increased incidence of infections when patients were treated with alefacept 30 mg compared with the 15 mg dose. The increased dose of alefacept 30 mg for the last 6 weeks of a 12-week course did not appear to yield a higher efficacy rate compared with historical controls.

Use of extended courses of alefacept in the treatment of moderate-to-severe psoriasis

Use of extended courses of alefacept in the treatment of moderate-to-severe psoriasis

Multiple courses of alefacept for the treatment of psoriatic nail disease in patients with chronic plaque psoriasis

Multiple courses of alefacept for the treatment of psoriatic nail disease in patients with chronic plaque psoriasis

Therapeutic effects of a 12‐week course of alefacept on nail psoriasis

Nail psoriasis is a common finding in psoriatic patients and it affects the quality of life in a great proportion of patients. Topical or systemic treatments have limited effectiveness or have a serious toxicity potential. Biologicals such as alefacept are the most recent treatment modalities for psoriasis. In the present study we evaluated changes in nail pathology in patients with plaque psoriasis and nail involvement during treatment with alefacept. Digital photographs from eight patients were produced, which were analysed using the nail psoriasis severity index (NAPSI). A minimal NAPSI of 15 was chosen to divide patients into a moderate to very severe nail psoriasis group and a group with no or mild nail psoriasis. A decrease in NAPSI of at least 25% was considered a significant response to therapy. In the group with at least moderate nail psoriasis, two patients improved, in two patients the nail changes remained unchanged and in one patient the nail pathology was aggravated. The group with no or mild nail psoriasis showed variable results. Although alefacept showed some results in treating nail pathology in psoriasis, a more extensive study is required, covering both more patients and a more extensive time period. Furthermore, it would also be clinically relevant to compare the effects of alefacept on nail psoriasis with other biologicals.

The long-term efficacy and safety of new biological therapies for psoriasis.

Long-term therapy is often required for psoriasis. This article reviews the most recent long-term clinical data for biological agents that have been approved or for which late-stage development data have been released for the treatment of patients with moderate to severe plaque psoriasis. Efficacy data are available for up to five 12-week courses of alefacept (approximately 60 weeks of therapy), 36 months (144 weeks) of continuous efalizumab, 48 weeks of continuous etanercept, and 50 weeks of bimonthly infliximab. Data sources include publications, product labeling, and posters presented at recent international scientific meetings. Alefacept appears to continue to be efficacious over multiple treatment courses for some responsive patients. The efficacy of efalizumab achieved during the first 12–24 weeks of therapy appears to be maintained or improved through at least 60 weeks of continuous treatment. The efficacy of etanercept appears to be maintained through at least 48 weeks of continuous treatment. Infliximab demonstrates a high response rate soon after initiation, which appears to be maintained through 24 weeks but declines modestly with therapy out to 50 weeks. After 48 weeks, approximately 60% of efalizumab-treated and 45% of etanercept-treated patients remaining on therapy achieved ≥75% improvement from baseline in Psoriasis Area and Severity Index, as did 70.5% of infliximab patients who did not miss more than two infusions. Safety data suggest that these agents may be used for long-term administration. Long-term data from psoriasis trials continue to accumulate. Recent data suggest that biological therapies have efficacy and safety profiles suitable for the long-term treatment of patients with moderate to severe psoriasis.

The efficacy of multiple courses of alefacept in patients with moderate to severe chronic plaque psoriasis

Among patients with psoriasis who did not achieve Psoriasis Area and Severity Index 50 during the first course of alefacept therapy, 53% achieved Psoriasis Area and Severity Index 50 during the second course (odds ratio [95% confidence interval] vs placebo 2.30 [1.26-4.19]). Alefacept provided incremental efficacy over 5 successive 12-week treatment courses.