The efficacy of efalizumab for the treatment of adults with moderate to severe psoriasis () was evaluated in 3 large phase III studies (Gordon et al 2003
; Lebwohl et al 2003
; Leonardi et al 2005
). Of these studies, 2 also had extension phases lasting an additional 12 weeks (Leonardi et al 2005
; Menter et al 2005
). In addition, an open-label study investigating the long-term efficacy was initiated (Gottlieb et al 2004). The phase III study by Lebwohl and colleagues (Lebwohl et al 2003
) was divided into three phases: a treatment phase from weeks 0 to 12, an extended treatment phase from weeks 13 to 24, and lastly a follow-up phase from weeks 25 to 36. Two of these studies, one by Lebwohl et al (2003
), the other by Leonardi and colleagues (2005)
, subjects received efalizumab 1 or 2 mg/kg or placebo subcutaneously, after a first dose of 0.7 mg/kg to reduce first dose adverse events. In the other phase III study by Gordon et al (2003)
, subjects received efalizumab 1.0 mg/kg subcutaneously or placebo. In the 3-year long-term study, patients were randomized to receive 12 weeks of open-label efalizumab 2.0 mg/kg once weekly with or without topical fluocinolone ointment (0.025%) during weeks 9 through 12. After these 12 weeks, patients with a PASI score reduction of 50% (PASI-50) were then scheduled to receive efalizumab 1.0 mg/kg once weekly for up to 33 months. Patients that relapsed during the maintenance phase were switched to once-weekly dosing of 2.0 mg/kg for 12 weeks or 4.0 mg/kg for 4 weeks. In the extension study by Menter et al (2006)
, all the patients that finished the initial 12-week double-blind phase received efalizumab 1.0 mg/kg/week for a further 12 weeks. Another extension phase by Leonardi et al (2005)
, patients who received efalizumab previously with PASI score reductions less than 75% were then re-randomized to receive placebo or continue on their previously administered dose of efalizumab at 1.0 or 2.0 mg/kg/week.
All of the phase III, double-blind studies used PASI score reductions of 75% (PASI-75) after 12 weeks of treatment as the primary efficacy endpoint. In the long-term study by Gottlieb et al (2006)
, in addition to PASI-75, PASI-50 and PASI-90 scores were examined.
The study by Gordon and colleagues (2003)
found that all efalizumab-treated patients experienced statistically significant improvement on all end points than those patients receiving placebo. Twenty-seven percent of patients receiving efalizumab achieved PASI-75 versus 4% of the placebo group. In addition, 95% of efalizumab-treated patients achieved PASI-50 compared with 14% of those receiving placebo. With regard to patient reported outcomes, at week 12, patients treated with efalizumab had a greater mean percentage improvement in DLQI with 47% compared with 14% in the placebo group. Efalizumab treatment also produced a 38% improvement in Itching Visual Analog Score (VAS) compared with placebo. Lastly, efalizumab-treated patients had statistically significant improvement in Psoriasis Symptom Assessment (PSA), both frequency and severity subscales (48% vs 18% and 46% vs 17%, respectively), compared with placebo.
In the extension study published by Menter and colleagues (Menter et al 2005
), of the 342 subjects who received and completed the 12-week course of efalizumab treatment, 342 enter an open-label treatment period for an additional 12 weeks, receiving 1 mg/kg/week. In addition, 174 subjects who completed a 12-week course of placebo were schedules to receive 12 weeks of efalizumab at the same dose. As the duration of treatment continued, PASI indexes continued to improve. At week 24, 66.6% of the previously efalizumab-treated patients achieved a PASI-50 response, and 43.8% achieved a PASI-75 response. The percentage of patients who achieved a static Physician’s Global Assessment (sPGA) of minimal or clear increased from 25.7% to 35.9% from week 12 to 24. For those subjects who received placebo followed by efalizumab, 28.7% achieved a sPGA rating of minimal or clear after 12 weeks. In addition to physician-assessed parameters, there was a statistically significant improvement after 12 weeks of efalizumab treatment in DLQI, Itching scale, and PSA frequency and severity.
In a study by Lebwohl and colleagues (2003
), patients receiving 1 mg/kg/week of efalizumab achieved PASI-75 in 22% of the subjects and in 28% of those subjects receiving 2 mg/kg/week, compared with 5% of those subjects receiving placebo. In the extended treatment phase, those subjects achieving PASI-75 or PASI-50 were randomly assigned to continue receiving 2 mg/kg of efalizumab weekly or every other week or placebo. Those subjects not attaining at least PASI-50 were randomly assigned to either an increased dose of 4 mg/kg of efalizumab weekly or placebo. It was found in the extended treatment phase that the efalizumab-treated subjects who initially achieved a PASI-75, a greater proportion of the subjects who received further treatment with efalizumab maintained a PASI-75 compared with those receiving placebo (p < 0.001). Of those subjects who did not achieve a PASI-50 on initial efalizumab treatment, an improvement of 75% or more was achieved in 40% of those subjects receiving efalizumab 4 mg/kg/week, compared with 15% in the placebo group (p = 0.02).
At the 36-week follow-up, 12 weeks after the discontinuation of study treatment, it was found that in subjects who received at least 50% improvement in their PASI index at week 24, the time to relapse (loss of at least 50% of the improvement in the PASI index that had been achieved between base line and week 24) was approximately 84 days.
Leonardi and colleagues (2005
) assessed short-term and extended-treatment efficacy and safety of efalizumab in another phase III study. The study was divided into 3 12-week treatment periods, the first from weeks 1 to 12, and retreatment or extended treatment periods during weeks 13 to 24, with 2 observation periods, with subjects receiving an initial treatment of efalizumab 1 mg/kg/week, 2 mg/kg/week, or placebo. During the first treatment week after 12 weeks, significantly more patients receiving 1 mg/kg and 2 mg/kg achieved a PASI-75 (39% and 27%, respectively) compared with those subjects receiving placebo (2%). Those efalizumab-treated subjects who did not achieve PASI-75 were re-randomized at week 12 to receive efalizumab or placebo for an extended 12-week period. At week 24, 20.3% of subjects who received an additional 12 weeks of efalizumab achieved a PASI-75 compared with 6.7% of those receiving placebo.
Gottlieb and colleagues assessed long-term, continuous therapy with efalizumab in a multicenter, open-label, phase III study in patients with moderate to severe chronic plaque psoriasis. Results for the first 27 months of this 36-month continuous therapy trial are available (Gottlieb et al 2006
). These data document that once-weekly subcutaneous efalizumab maintains sustained efficacy without toxicity. Patients were randomized to receive 12 weeks open-label subcutaneous efalizumab 2.0 mg/kg/week with or without topical fluocinolone during weeks 9 to 12. After the 12th week, patients were then scheduled to receive efalizumab, 1.0 mg/kg/week for up to 33 weeks, if they received at least a PASI-50 during the first 12 weeks of treatment. If a patient relapsed, therapy was increased to 2.0 mg/kg/week for 12 weeks or 4.0 mg/kg/week for 4 weeks. Concomitant topical corticosteroids and UVB phototherapy were also permitted. PASI improvement was maintained throughout the 27-month period.