Drug Evaluation

10.1517/14656566.6.13.2327 © 2005 Ashley Publications Ltd ISSN 1465-6566 2327

Ashley Publicationswww.ashley-pub.com

Alefacept: an expert review concerning the treatment of psoriasisRichard G Langley†, Andréa M Cherman & Aditya K Gupta†Dalhousie University, Room 121, Center for Clinical Research, 5820 University Avenue, Halifax, NS, B3H 1V7, Canada

Psoriasis is a chronic, inflammatory skin disease. Historically, phototherapy orimmunosuppressive agents have been the first line of treatment for patientswith severe psoriasis; however, the long-term use of these agents is limited bydose-dependent toxicities. Alefacept was the first biological agent approvedin both the US and Canada for the treatment of adults with moderate-to-severe chronic plaque psoriasis. Alefacept is a remittive therapy that selec-tively reduces memory T cells. The efficacy and safety of up to two courses ofalefacept have been demonstrated in clinical trials, and thus, this reviewfocuses on new data to optimise the use of this biological agent. Emergingdata indicates that multiple courses of alefacept for the long-term treatmentof psoriasis are safe and effective. In addition, data are reviewed on the use ofalefacept in combination with other agents and in other diseases, includingpsoriatic arthritis.

Keywords: alefacept, biologicals, psoriasis

Expert Opin. Pharmacother. (2005) 6(13):2327-2333

1. Introduction

Psoriasis is a chronic, T-cell-mediated disease with significant negative physical andemotional impact. It affects ∼ 2.6% of the US population, and ≤ 4% of the popula-tion worldwide [1]. Disease severity varies depending on inheritance and environ-mental factors [2,3], with ∼ 25% of patients diagnosed as moderate-to-severe [4], and≤ 15 – 30% diagnosed with psoriatic arthritis [5]. As there is no cure for psoriasis [6],there is a definite need for effective treatments that are safe for long-term use. Untilrecently, psoriasis therapy centred on phototherapy (narrowband and broadbandultraviolet B [UVB], psoralen plus ultraviolet A [PUVA]) and systemic treatments,such as methotrexate, cyclosporin, oral retinoids and 6-azathioprine, which havelimitations that often prevent their long-term use. Recent advances in psoriasis treat-ment have focused on the development of biological agents that target the key stepsin the inflammatory cascade of events that lead to the formation of psoriaticplaques. Through selective, immunologically directed intervention, these agentsprovide safe and effective psoriasis treatment and address some of the limitations oftraditional therapy.

2. Challenges of current therapy

Although traditional systemic agents are effective for the treatment of psoriasis, they areprimarily suppressive treatments that require continuous administration. This is prob-lematic, given the increasing risk of toxicity with long-term use, and the risk of diseaserebound when treatment is discontinued [7]. Cyclosporin (> 5 mg/kg) can cause func-tional and structural damage to the kidney with hypertension and renal toxicity, whichgenerally limits its use to short-term therapy (≤ 12 months) [8]. Methotrexate, the mostwidely used systemic psoriasis treatment, may cause hepatotoxicity, bone marrow

1. Introduction

2. Challenges of current therapy

3. Alefacept

4. Expert opinion

Exp

ert O

pin.

Pha

rmac

othe

r. D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y T

ufts

Uni

vers

ity o

n 12

/09/

14Fo

r pe

rson

al u

se o

nly.

Alefacept

2328 Expert Opin. Pharmacother. (2005) 6(13)

toxicity and pneumonitis [9]. With long-term use (> 5 years),methotrexate can cause cirrhosis and portal fibrosis in > 25% ofpatients [9]. The use of phototherapy is also limited; long-termPUVA treatment increases the risk of nonmelanoma skin cancer(especially squamous cell carcinoma) and possibly melanoma,particularly in patients with Fitzpatrick type I or II skin whohave had > 200 treatments [10]. UVB does not increase the riskof systemic malignancy, but the frequent treatment schedulemakes it an inconvenient option for many patients.

In addition, patient satisfaction with treatment is a concern,as a survey of the National Psoriasis Foundation showed that∼ 23% of patients with psoriasis are very dissatisfied with theiroverall psoriasis treatment, where 50% reporting dissatisfactionhad moderate-to-severe psoriasis [5]. Taken together, it is evidentthat there exists an unmet need for therapies that have longer-lasting efficacy and fewer side effects in the management ofpatients with moderate-to-severe psoriasis [11].

3. Alefacept

Alefacept is the first biological to be approved in the US(2003) and Canada (2004) for the treatment of patients withmoderate-to-severe chronic plaque psoriasis who are candi-dates for systemic therapy or phototherapy [12]. Alefacept isadministered by intramuscular injection. The recommendeddose is 15 mg/week for 12-weeks, with 12 week intervalsbetween courses.

3.1 Structure and mechanism of actionAlefacept is a fully human dimeric fusion protein composedof the extracellular CD2 binding portion of the human leuko-cyte function antigen-3 (LFA-3) fused to the Fc portion of thehuman IgG1 hinge, CH2 and CH3 domains [13]. Alefacepthas a dual mechanism of action: it inhibits T-cell activationand depletes memory T cells.

CD2 is a T-cell surface protein, which, when bound toLFA-3 on antigen-presenting cells (APCs), usually delivers oneof the costimulatory signals necessary for full T-cell activation.The LFA-3 portion of alefacept binds to CD2 on the surfaceof T cells and thereby blocks the interaction of CD2 withLFA-3 on APCs, inhibiting the activation of T cells. In addi-tion, the Fc portion of alefacept binds to FcγRIII receptors onaccessory cells, such as natural killer (NK) cells and macro-phages, causing granzyme-mediated apoptosis and the deple-tion of memory-effector T cells in the peripheral circulation[14,15] and lesional psoriatic skin [16].

3.2 Pharmacokinetics and pharmacodynamicsSerum concentrations of alefacept are detectable ∼ 6 h afterintramuscular injection, and peak concentrations areachieved between 24 and 192 h [17]. Once absorption iscomplete, the elimination of alefacept from the serum has ahalf-life of ∼ 12 days [17].

The mechanism of action of alefacept results in decreasedlymphocyte counts. After a single dose, lymphocyte counts

are reduced from 1 to 35% of baseline within 24 h but thechanges are transient [17]. Absolute lymphocyte countsremained above normal and lymphocyte subset counts (i.e.,CD2+, CD3+, CD4+, CD8+ and CD19+) that decreased at24 h, subsequently returned toward baseline [17].

In Phase II studies, flow cytometry was performed to quan-tify populations of all cells that express varying amounts ofCD2 on their surface including CD4+, CD8+, CD45RO+ andCD45RA+ lymphocytes, as well as CD19+ B cells, CD16+ andCD56+ NK cells [15]. It was found that there was a dose-dependent reduction in memory T cells (CD4+CD45RO+

and CD8+CD45RO+) following the administration of ale-facept [15]. This reduction was selective to memory T cells(CD45RO+) as the naive T cells (CD45RA+) did not substan-tially change, which indicates a targeted reduction of patho-genic T cells [15]. This reduction in memory T cells correlatedwith overall improvement of psoriasis [15].

To ensure that host immune responses were not adverselyaffected by alefacept-induced reductions in memory T cells,the effect of alefacept treatment on primary and secondaryimmune responses to newly encountered antigen (øX174)and acquired immune response to recall antigen (tetanus tox-oid) was assessed in a multi-centre, randomised, open-label,parallel-group Phase II trial [18]. This study demonstratedthat patients maintain an intact immune response during andafter clinically effective doses of alefacept administered onceweekly for 12 weeks.

Due to the effect of alefacept on memory T cells, patientsshould have normal CD4+ lymphocyte counts (> 400 cells/µl)prior to treatment initiation [12]. Dosing should be withheld ifthese counts fall < 250 cells/µl and discontinued if the countsremain below that level for 1 month [12]. Although the USpackage labelling recommends weekly monitoring of CD4+

lymphocyte counts during a treatment course, alternativeT-cell monitoring schedules are also being evaluated. In othermarkets (Canada, Switzerland, Australia), the labelling recom-mends T cells to be monitored every other week. An open-label study found that T-cell monitoring every other week didnot alter the maximum effect of alefacept on, or the recoveryof, CD4+ T-cell counts and did not lead to an increase in thenumber of cases of extremely low CD4+ T-cell counts(< 200 cells/µl) [19]. The incidence of adverse events, infec-tions and malignancies during every other week monitoringwas low and comparable to those seen during weekly moni-toring [19]. Additional studies are currently underway tofurther assess the T-cell monitoring schedule.

3.3 EfficacyThe efficacy of up to two courses of alefacept has beendescribed in detail in reports of Phase II and III clinical trials(Table 1) [15,20-22]. In a Phase II, multi-centre, double-blind,placebo-controlled study, patients (n = 229) were randomisedto receive intravenous alefacept or placebo weekly for 12 weekswith 12 weeks of follow up [15]. Three doses of alefacept wereevaluated; results of the dose (0.075 mg/kg i.v.) that most

Exp

ert O

pin.

Pha

rmac

othe

r. D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y T

ufts

Uni

vers

ity o

n 12

/09/

14Fo

r pe

rson

al u

se o

nly.

Langley, Cherman & Gupta

Expert Opin. Pharmacother. (2005) 6(13) 2329

closely approximates the marketed dose are summarised below.A total of 60% of alefacept-treated patients achieved a ≥ 50%reduction in the Psoriasis Area and Severity Index (PASI 50)two weeks after treatment, compared with 27% of placebo-treated patients (p < 0.001)). In addition, 33% of patientsreceiving alefacept had a ≥ 75% PASI reduction (PASI 75),compared with 10% of placebo-treated patients (p < 0.001).

In a subsequent multi-centre, double-blind, placebo-con-trolled Phase III study (n = 553), two 12-week courses of ale-facept 7.5 mg/week i.v. or placebo were administered with aninterval of 12 weeks between each course [20]. In both courses,alefacept produced a mean decrease in PASI that peaked8 weeks after the treatment course. At 2 weeks after treatmentwith one course, PASI 75 and 50 were obtained by 14 and38% of alefacept-treated patients compared with 4 and 8% ofplacebo-treated patients. During treatment and follow up ofthe first course, PASI 75 and 50 were achieved by 28 and 56%of alefacept-treated patients, respectively, compared with 8and 24% of placebo-treated patients (p < 0.001). Amongpatients who received two courses of alefacept, 40 and 71%achieved PASI 75 and 50, respectively during the secondcourse of treatment.

The efficacy of intramuscular alefacept was demonstrated ina Phase III randomised, multi-centre, double-blind, placebo-controlled study [21] and its extension [22]. Patients (n = 507)were randomised to receive alefacept 15 mg/week or placebofor 12 weeks with a 12-week follow-up period. At 2 weeksafter one course of intramuscular alefacept 15mg, 14% ofpatients attained a PASI 75. The proportions of alefacept-treated patients that attained a PASI 75 and 50 response dur-ing treatment and follow up after the first course of treatmentwere 33 and 57%, respectively, compared with 13 and 35% forthe placebo group (p < 0.001) [21].

A second course of alefacept significantly improves clinicaloutcomes in patients, regardless of their response to the ini-tial treatment [23]. Following a second course of intravenous

alefacept, PASI 50 and 75 were achieved by 53 and 19% ofpatients, respectively, who had initially failed to achievePASI 50 after one course. Improvement was also seen inpatients who had initially failed to achieve PASI 25; 47%achieved PASI 50 and 14% achieved PASI 75 following asecond course of treatment [23].

Data collected following multiple courses of alefacept indi-cate its efficacy for the long-term treatment of chronic plaquepsoriasis (Table 2) [23]. In an analysis of patients who com-pleted up to five courses of intravenous alefacept, incremen-tal improvements in efficacy were seen following eachsubsequent course, with the proportion of patients whoachieved PASI 75 increasing from 29% after one course ofintravenous alefacept to a maximum of 54% following fivecourses [23]. Similarly, the proportion of patients achieving aPhysician’s Global Assessment (PGA) of ‘clear/almost clear’increased from 21% during the first course of intramuscularalefacept to a maximum of 41% during the fourth course.

3.4 Duration of off-treatment responseThe advantage of remittive agents such as alefacept is that theyoffer the potential for patients to maintain a clinical responseeven after treatment has been discontinued. Clinical trial dataindicate that alefacept induces a durable remission, defined asthe period of time that patients maintain at least a PASI 50response after achieving PASI 75 [20]. The median duration ofremission in responding patients after the first course of treat-ment was 216 days in the Phase III intravenous study [20] and209 days in the Phase III intramuscular study [22].

3.5 Extended dosing regimensClinical improvements in psoriasis continue after patients com-plete an alefacept treatment course [20-22]; therefore, extendeddosing regimens may provide additional benefits. In an open-label study evaluating 16 weeks of intravenous alefacept treat-ment (n = 39), PASI 50 was achieved by 46% of patients, andPASI 75 by 21% [24]. The extended dosing regimen was welltolerated, with an adverse event profile consistent with that of a12-week intravenous treatment course [20]. Similar results wereseen when the efficacy and safety of an additional 4 weeks ofintramuscular alefacept were evaluated in seven patients whofailed to achieve PASI 75 after 12 weeks of treatment [25]. Sig-nificant improvements in PASI scores were seen 2 weeks follow-ing the completion of the 16-week treatment course, and nosafety concerns were identified.

Results of an interim analysis of another trial evaluating16 weeks of intramuscular alefacept also suggest that this regi-men has the potential to improve response, with the mean per-centage reduction in PASI scores from week 12 to 20 and 24being higher for patients receiving 16 weeks of therapy com-pared with those receiving 12 weeks (39 versus 14% at week20, 36 versus 2% at week 24; both p < 0.05) [26]. In addition,there were no statistically significant differences seen in the fre-quency of adverse events between the two regimens [26].Research evaluating alternate dosing regimens is underway;

Table 1. Efficacy of up to two courses of alefacept for the treatment of psoriasis.

Study Course one Course two

PASI 50 PASI 75 PASI 50 PASI 75

Phase II: alefacept 0.075 mg/kg i.v.(% responders) [15]

60 33 – –

Phase III: alefacept 7.5 mg i.v.(% responders) [20]

38 14 48 23

Phase III: alefacept 15 mg i.m.(% responders) [21,22]

42 21 59 31

Efficacy was assessed 2 weeks after completion of each 12-week alefacept treatment course.PASI: Psoriasis Area and Severity Index.

Exp

ert O

pin.

Pha

rmac

othe

r. D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y T

ufts

Uni

vers

ity o

n 12

/09/

14Fo

r pe

rson

al u

se o

nly.

Alefacept

2330 Expert Opin. Pharmacother. (2005) 6(13)

this information, coupled with the preliminary data presentedhere, will help to tailor alefacept dosing to further improvepatient outcomes.

3.6 Combination therapyThe safety and efficacy of alefacept in combination witheither narrowband or broadband UVB were evaluated in anopen-label pilot study (n = 60) [27]. Patients who receivedeither narrowband or broadband UVB in combination withalefacept achieved a greater degree of clinical improvementmore rapidly than patients who received alefacept mono-therapy [27]. In addition, the combination of alefacept andUVB was well tolerated, with adverse events similar to thoseencountered when either treatment was used alone.

The combination of alefacept and etanercept in twopatients who did not fully respond to etanercept mono-therapy has recently been reported [28]. The combination waswell tolerated, and the addition of alefacept resulted in sub-stantial improvement of psoriatic plaques that were previouslyunresponsive to etanercept.

An international study, Clinical Long-Term AlefaceptRepeat-Course Intramuscular Therapy (CLARITY), is beingconducted under clinical practice conditions to examine thesafety and efficacy of up to three courses of intramuscularalefacept combined with other psoriasis therapies [29]. Inaddition to alefacept, patients can receive low- or high-potency topical steroids, methotrexate, cyclosporin, UVB,systemic retinoids or prednisone. During the first-coursetherapy across all treatment groups, 71% of patients experi-enced a PGA improvement of ≥ 1 category, and an improve-ment of ≥ 2 categories was seen in 44% of patients.Preliminary data indicates that adverse events are similar tothat observed in the pivotal trials of alefacept monotherapy[20,21], with a very low incidence of serious infection (0.7%).No opportunistic infections were reported [29]. In addition,no significant laboratory abnormalities have been reported,

indicating that the addition of alefacept does not increasethe incidence of liver toxicity from methotrexate or the renaltoxicity from cyclosporin [29].

3.7 Transition from other agentsStrategies for transitioning patients from conventional sys-temic agents to alefacept are being evaluated in two open-label studies [21,30]. In one study (n = 12), alefacept wasadministered once weekly for 12 weeks while the methotrex-ate dose was tapered over ∼ 8 weeks, with the goal of discon-tinuing methotrexate completely [30]. The majority of thepatients (83%; 10/12) were able to transition off methotrex-ate while maintaining or improving their PASI scores [30]. Noclinical adverse events or remarkable changes in liver functiontests were reported during the study.

Another study is evaluating the transitioning fromcyclosporin to alefacept (n = 11) [31]. During the first 4 weeksof alefacept treatment, cyclosporin is continued at the lowestdose at which psoriasis was well controlled prior to studyentry. During weeks 5 – 8 of alefacept therapy, thecyclosporin dose is tapered to 3 mg/kg/day (if initial dose> 3 mg/kg/day) or remains at 2.5 mg/kg/day, if already atthis level. Over the following 9 – 12 weeks, the cyclosporindose is further reduced to 2.5 mg/kg/day, if not alreadyreduced to this level [31]. Cyclosporin is discontinued afterweek 12, and patients enter a 12-week, treatment-free obser-vation period. Preliminary results demonstrated that thePGA scores remain stable during the tapering of cyclosporin,with no evidence of disease flare or rebound [31].

Clinical experience is consistent with these results, as thesuccessful transition of patients from methotrexate orcyclosporin during alefacept therapy has been reported [32]. Atotal of 29 patients were able to discontinue methotrexatetherapy while on alefacept, and 17 patients transitioned offcyclosporin. Over 75% of these patients experienced at least a25% improvement in their psoriasis during alefacept treat-ment [32]. The successful transitioning of patients off conven-tional therapies has many potential advantages, includinglimiting patient exposure to these agents, thereby decreasingthe risk of dose-related organ toxicity.

3.8 Potential therapeutic applicationsEvidence suggests that alefacept may have clinical utility inseveral areas in addition to chronic plaque psoriasis. A ran-domised, controlled, Phase II study evaluated the safety andefficacy of a standard 12-week alefacept treatment course incombination with methotrexate for the treatment of psori-atic arthritis (n = 185) [33]. The primary efficacy end pointwas the proportion of patients achieving a 20% reduction inAmerican College of Rheumatology core set measurements(ACR 20) 12 weeks after the completion of alefacept ther-apy. Preliminary results demonstrated that a significantlygreater proportion of patients in the alefacept-methotrexategroup achieved ACR 20 (54%) than those who receivedmethotrexate alone (23%; p < 0.001) [33]. Adverse events

Table 2. Efficacy of multiple courses of alefacept therapy [23].

Treatment course

1 2 3 4 5

Alefacept 7.5 mg i.v.

n = 521 n = 327 n = 217 n = 158 n = 39

PASI 50 (%) 56 62 65 67 74

PASI 75 (%) 29 37 43 44 54

PGA ‘clear/almost clear’ (%)

23 31 34 35 44

Alefacept15 mg i.m.

n = 457 n = 320 n = 156 n = 100 n = 50

PGA ‘clear/almost clear’ (%)

21 26 36 41 28

PASI: Psoriasis Area and Severity Index; PGA: Physician’s Global Assessment.

Exp

ert O

pin.

Pha

rmac

othe

r. D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y T

ufts

Uni

vers

ity o

n 12

/09/

14Fo

r pe

rson

al u

se o

nly.

Langley, Cherman & Gupta

Expert Opin. Pharmacother. (2005) 6(13) 2331

were similar between treatment groups, with no significantsafety concerns noted.

Palmoplantar pustular psoriasis (PPP), which is character-ised by recurrent sterile pustules on the palms and soles, is verydifficult to treat. A recently presented case report documentsthe effect of alefacept on a patient with severe PPP [34]. Thepatient received a total of 17 doses of alefacept (12-week stand-ard course, followed by an additional 5 doses 1 month later)and experienced extensive improvement of the lesions on hispalms and soles, including marked reductions in erythema,scale and the number of pustules. The patient achieved near-clearance of all lesions 12 weeks after the last alefacept dose,and clinical response to treatment was maintained for a total of19 weeks following the completion of treatment.

Nail psoriasis is also very difficult to treat; therefore, theefficacy of alefacept for the treatment of nail psoriasis wasevaluated in an open-label trial (n = 15) [35]. A mediandecrease of 38% was seen in the Nail Psoriasis Severity Index,with 33% of patients achieving ≥ 50% reduction. The evalua-tion of alefacept is ongoing and additional information is nec-essary to corroborate the results discussed here; however,preliminary data indicate that alefacept may be an effectivetherapeutic option for patients with these conditions.

3.9 Safety and tolerabilityThe safety and tolerability of up to two courses of alefacept inPhase II and III clinical trials has previously been reported indetail [15,20-22]. A total of 1869 patients in the alefacept clinicaltrial programme have received at least one course of alefacept.The most commonly reported (≥ 5% incidence) adverseevents during the first course of alefacept treatment were head-ache (14%), nasopharyngitis (10%), influenza (8%), upperrespiratory tract infection (URI) (8%) and pruritus (8%) [36].Infections occurred in 47% of patients; the most commoninfections were nasopharyngitis, influenza and URI that weremild-to-moderate in severity and were resolved with conven-tional treatment. The overall rate of serious infection was verylow (0.7%), as was the incidence of malignancies (1.3%), themajority of which were nonmelanoma skin cancer.

Safety data are available for patients who have received upto nine courses of alefacept [36]. The overall incidence ofadverse events did not increase with multiple courses, and themost commonly reported events (headache, nasopharyngitis,influenza, prurtitis, URI, arthralgia) were similar betweencourses. The incidence of serious adverse events and malig-nancies did not increase with multiple courses of therapy.

The multiple-course exposure did not increase the incidenceof infections, and no correlation was observed between theincidence of infections and CD4+ T-cell counts. There wereno reports of opportunistic infections during any treatmentcourse. The overall incidence of antibody formation was verylow, and did not increase despite intermittent exposure toalefacept over several treatment courses. No hypersensitivityreactions or safety issues were associated with antibody for-mation. These data suggest that alefacept is a safe option forthe long-term treatment of psoriasis.

The safety of alefacept in special populations, includingelderly, diabetic and obese patients has also been evaluated[37]. Given the risk of comorbidities in these patients, thesafety of psoriasis therapies is a substantial concern. The mostcommon adverse events seen in these populations were similarto those in the Phase III trials, and included accidental injury,headache, pharyngitis, rhinitis and infection. There was noapparent association between CD4+ counts and infections,and the overall incidence of infections and malignancy wassimilar to that seen in the general population. The incidenceof adverse events, infections and malignancy did not appear toincrease with multiple courses of therapy, suggesting that ale-facept is a safe option for the long-term treatment of psoriasisin the elderly, diabetic and obese patient populations [37].

4. Expert opinion

Alefacept is a biological agent for psoriasis that selectivelyreduces memory T cells and has demonstrated efficacy andsafety in clinical trials with a durable response. This agent isrelatively simple to use with a convenient dosing and moni-toring schedule. Alefacept has several advantages for patientswith psoriasis: it may provide long remissions without theneed for maintenance therapy; its efficacy increases with sub-sequent courses, and it maintains an excellent safety profileduring long-term treatment.

Although this agent has been well studied using a 12-weekdosing regimen, ongoing work evaluating extended dosingregimens and the use of alefacept in combination with otherpsoriasis therapies may help to define treatment regimens thatoffer the potential for incremental improvements in responserates. In addition, emerging data indicates that alefacept mayprovide clinical benefit to patients with other psoriasis-relateddisorders, including psoriatic arthritis and nail psoriasis; how-ever, further investigation is necessary to more fully evaluateits efficacy in these patients.

BibliographyPapers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers.

1. KRUEGER JG: The immunologic basis for the treatment of psoriasis with new biologic

agents. J. Am. Acad. Dermatol. (2002) 46:1-23

•• Comprehensive, state-of-the-art review on the pathophysiology of psoriasis.

2. LEBWOHL M: Psoriasis. Lancet (2003) 361:1197-1204

3. ELDER JT, NAIR R, HENSLER T et al.: The Genetics of Psoriasis 2001. Arch. Dermatol. (2001) 137:1447-1454.

4. CHAUDHARI U, ROMANO P, MULCAHY LD et al.: Efficacy and safety of infliximab monotherapy for plaque type psoriasis: a randomised trial. Lancet (2001) 357:1842-1847.

Exp

ert O

pin.

Pha

rmac

othe

r. D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y T

ufts

Uni

vers

ity o

n 12

/09/

14Fo

r pe

rson

al u

se o

nly.

Alefacept

2332 Expert Opin. Pharmacother. (2005) 6(13)

5. National Psoriasis Foundation 2001 Benchmark Survey on Psoriasis and Psoriatic Arthritis. National Psoriasis Foundation (2001).

6. GEILEN CC, ORFANOS CE: Standard and innovative therapy of psoriasis. Clin. Exp. Rheumatol. (2002) 20(Suppl. 28):S81-S87.

7. KRUEGER GG, ELLIS CN: Alefacept therapy produces remission for patients with chronic plaque psoriasis. Br. J. Dermatol. (2003) 148(4):784-788.

8. GRIFFINS CEM, DUBERTRET L, ELLIS CN et al.: Ciclosporin in psoriasis clinical practice: an international consensus statement. Br. J. Dermatol. (2004) 150(Suppl. 67):11-23.

9. THEMIDO R, LOUREIRO M, PECEGUEIRO M, BRANDAO M, CAMPOS MC: Methotrexate hepatotoxicity in psoriatic patients submitted to long-term therapy. Acta Derm. Venereol (1992) 72(5):361-364.

10. LEBWOHL M, ALI S: Treatment of psoriasis. Part 1. Topical therapy and phototherapy. J. Am. Acad. Dermatol. (2001) 45(4):487-498.

11. KRUEGER GG, CALLIS KP: Development and use of alefacept to treat psoriasis. J. Am. Acad. Dermatol. (2003) 49(2 Suppl.):S87-S97.

12. Prescription Information: Amevive® (alefacept) BiogenIdec, Inc. Cambridge, MA, USA (2004).

13. MILLER GT, HOCHMAN PS, MEIER W et al.: Specific interaction of lymphocyte function-associated antigen 3 with CD2 can inhibit T cell responses. J. Exp. Med. (1993) 178(1):211-222.

14. KIRBY B, GRIFFITHS CEM: Novel immune-based therapies for psoriasis. Br. J. Dermatol. (2002) 146:546-551.

15. ELLIS CN, KRUEGER GG: Treatment of chronic plaque psoriasis by selective targeting of memory effector T lymphocytes. N. Engl. J. Med. (2001) 345(4):248-255.

•• Initial Phase II randomised, double-blind study of alefacept that provided key information on efficacy and safety of this drug.

16. CHAMIAN F, LOWES MA, LIN SL et al.: Alefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris. Proc. Natl. Acad. Sci. USA (2005) 102(6):2075-2080.

17. VAISHNAW AK, TENHOOR CN: Pharmacokinetics, biologic activity, and tolerability of alefacept by intravenous and intramuscular administration. J. Pharmacokinet. Pharmacodyn. (2002) 29(5-6):415-426.

18. GOTTLIEB AB, CASALE TB, FRANKEL E et al.: CD4+ T-cell-directed antibody responses are maintained in patients with psoriasis receiving alefacept: results of a randomized study. J. Am. Acad. Dermatol. (2003) 49(5):816-825.

19. LANGLEY R, BAKER D, ROBERTS J: The safety of alefacept using a reduced schedule for monitoring T cells. Presented at the American Academy of Dermatology meeting. Washington DC, USA (2004).

20. KRUEGER GG, PAPP K, STOUGH DB et al.: A randomized, double-blind, placebo-controlled, Phase III study evaluating efficacy and tolerability of 2 courses of alefacept in patients with chronic plaque psoriasis. J. Am. Acad. Dermatol. (2002) 47(6):821-831.

21. LEBWOHL M, CHRISTOPHERS E, LANGLEY R et al.: An international, randomized, double-blind, placebo-controlled Phase III trial of intramuscular alefacept in patients with chronic plaque psoriasis. Arch. Dermatol. (2003) 139(6):719-727.

• Pivotal, double-blind, randomised controlled study of intramuscular alefacept in the treatment of patients with chronic plaque psoriasis.

22. GORDON KB, LANGLEY RG: Remittive effects of intramuscular alefacept in psoriasis. J. Drugs Dermatol. (2003) 2(6):624-628.

23. MENTER A, BAKER D, FARBER H, LEBWOHL M: Long-term use of alefacept: efficacy and off-treatment responses in patients who have received multiple courses of therapy. Proceedings of the 63rd Annual meeting of the American Academy of Dermatology. New Orleans, LA, USA. J. Am. Acad. Dermatol. (2005) 52(3 Suppl. 1):P2.

24. KORMAN N, TICHO B: Weight-based and extended dosing as alternate alefacept treatment regimens for patients with psoriasis who weigh between 100 and 150 kg. Proceedings of the 63rd Annual Meeting of the American Academy of Dermatology. New Orleans, LA, USA. J. Am. Acad. Dermatol. (2005) 52(3 Suppl. 1):P202.

25. HOLZMAN G, PHILLIPS T: An extended 16-week course of alefacept in conjunction with reduced T-cell monitoring for the treatment of chronic plaque psoriasis. Proceedings of the 63rd Annual Meeting of the American Academy of Dermatology. New Orleans, LA, USA. J. Am. Acad. Dermatol. (2005) 52(3 Suppl. 1):P176.

26. GRIBETZ C, BLUM R, BRADY C, COHEN S, LEBWOHL M: Safety and efficacy of an extended 16-week course of alefacept in the treatment of chronic plaque psoriasis. J. Am. Acad. Dermatol. (2005) (In press).

27. ORTONNE JP, KHEMIS A, KOO J: An open label study of alefacept plus ultraviolet B light as combination therapy for chronic plaque psoriasis. J. Eur. Acad. Dermatol. Venereol. (2005) (In press).

28. KRELL J: Use of alefacept in 2 patients whose psoriasis failed to respond to etanercept. Poster presented at the American Academy of Dermatology meeting. New Orleans, LA, USA (2005).

29. GORDON K, KRUEGER G, VAN DE KERKOHF P, GOTTLIEB A: Efficacy and safety of multiple courses of alefacept in combination with other psoriasis therapies. Proceedings of the 63rd Annual Meeting of the American Academy of Dermatology. New Orleans, LA, USA. J. Am. Acad. Dermatol. (2005) 52(3 Suppl. 1):P183.

30. MENTER A, ABRAMOVITS W, CATHER JC: Transitioning patients with psoriasis from methotrexate to alefacept. Presented at the 10th International Psoriasis Symposium. Toronto, Canada. (2004).

31. MAGLIOCCO M, LOZANO A, VAN SADERS C, GOTTLIEB A: A safe and effective strategy for transitioning patients from cyclosporine to alefacept therapy. Proceedings of the 63rd Annual Meeting of the American Academy of Dermatology. New Orleans, LA, USA. J. Am. Acad. Dermatol. (2005) 52(3 Suppl. 1):P174.

32. CATHER JC, MEIER A, YOUNG M, MENTER A: Transitioning patients with psoriasis from conventional systemic psoriasis therapies to alefacept. Proceedings of the 63rd Annual Meeting of the American Academy of Dermatology. New Orleans, LA, USA. J. Am. Acad. Dermatol. (2005) 52(3 Suppl. 1):P200.

33. LEBWOHL M, MENTER A: The treatment of active psoriatic arthritis with

Exp

ert O

pin.

Pha

rmac

othe

r. D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y T

ufts

Uni

vers

ity o

n 12

/09/

14Fo

r pe

rson

al u

se o

nly.

Langley, Cherman & Gupta

Expert Opin. Pharmacother. (2005) 6(13) 2333

alefacept in combination with methotrexate: a randomized, double-blind, placebo-controlled study. Presented at the 29th Annual Hawaii Dermatology Seminar. Maui, HI, USA (2005).

34. YEUNG-YUE K, ARONSON P, MURAKAWA G: Clinical improvement of palmoplantar pustular psoriasis with alefacept. Proceedings of the 63rd Annual Meeting of the American Academy of Dermatology. New Orlenas, LA, USA. J. Am. Acad. Dermatol. (2005) 52(3 Suppl. 1):P179.

35. PARRISH C, ELEWSKI B, SOBERA J, CANTRELL W: The use of alefacept in the treatment of psoriasis of the nails. Proceedings of the 63rd Annual Meeting of the American Academy of Dermatology.

New Orleans, LA, USA. J. Am. Acad. Dermatol. (2005) 52(3 Suppl. 1):P199.

36. GOFFE B, PAPP K, GRATTON D, KRUEGER G: Long-term safety of alefacept in patients who have received up to nine courses of therapy. Proceedings of the 63rd Annual Meeting of the American Academy of Dermatology. New Orleans, LA, USA. J. Am. Acad. Dermatol. (2005) 52(3 Suppl.1):P190.

37. GOTTLIEB A: Safety and efficacy of alefacept in elderly patients and other special populations. Proceedings of the 63rd Annual Meeting of the American Academy of Dermatology. New Orleans, LA, USA. J. Am. Acad. Dermatol. (2005) 52(3 Suppl. 1):P175.

AffiliationRichard G Langley†1 MD, FRCP, Andréa M Cherman2 BSc & Aditya K Gupta3 MD, PhD, FRCP†Author for correspondence1Dalhousie University, Room 121, Center for Clinical Research, 5820 University Avenue, Halifax, NS, B3H 1V7, CanadaTel: +1 902 425 803; Fax: +1 902 421 1580; Email: richard.langley@dal.ca2Mediprobe Research Inc, London, Ontario, Canada3Division of Dermatology, Department of Medicine, Sunnybrook and Women’s College Health Sciences Centre (Sunnybrook site) and the University of Toronto, Canada

Exp

ert O

pin.

Pha

rmac

othe

r. D

ownl

oade

d fr

om in

form

ahea

lthca

re.c

om b

y T

ufts

Uni

vers

ity o

n 12

/09/

14Fo

r pe

rson

al u

se o

nly.