Efficacy and Safety of Efalizumab in Patients with Moderate-to-Severe Plaque Psoriasis Resistant to Previous Anti-Psoriatic Treatment: Results of a Multicentre, Open-label, Phase IIIb/IV Trial

Abstract

OBJECTIVES: To evaluate the efficacy and safety of efalizumab in continuous or interrupted therapy of adults with moderate-to-severe plaque psoriasis who had failed to respond to or were intolerant of other systemic therapies, including methotrexate, ciclosporin and psoralen plus UVA phototherapy, or for whom such therapies were contraindicated. METHODS: Patients received a conditioning dose of efalizumab 0.7 mg/kg followed by once-weekly open-label efalizumab 1.0 mg/kg for 11 weeks. Responders (Physician Global Assessment [PGA] score of "good" or better at Week 12) could continue efalizumab for a further 8 weeks (continuous-treatment period). Nonresponders transitioned to alternative anti-psoriasis medication or stopped treatment. Responders who discontinued efalizumab could restart treatment if symptoms worsened. PGA response was evaluated at Weeks 12 (primary endpoint) and 20, as were the proportions of patients achieving an improvement from baseline of >/=50%, >/=75% and >/=90% in Psoriasis Area and Severity Index (PASI) (PASI 50, PASI 75 and PASI 90, respectively). RESULTS: A total of 1,255 patients were included in the intention-to-treat population. At Week 12, 68.0% of patients had a PGA rating of "good" or better. Of 688 patients who entered the continuous-treatment period, 79.5% had a PGA rating of "good" or better at Week 20. At Week 12, median improvement in PASI score was 68.4%. PASI 50/75/90 was achieved by 65.5%/35.9%/13.0% of patients at Week 12, and by 78.2%/52.9%/24.3% of responders at Week 20. Of the 127 responders at Week 12 who discontinued efalizumab, 11% experienced rebound and 56.7% relapsed within 8 weeks after stopping therapy. Efalizumab was well tolerated during the study. CONCLUSIONS: Efalizumab provided effective control of psoriasis in the majority of patients during the initial treatment period. The high response rates were maintained in initial responders when treatment was continued beyond 12 weeks.

Figures

Figure 1

Trial design and patient disposition. White boxes indicate patients who entered inappropriate treatment or assessment periods based on their response status. CT = continuous-treatment; FT = first-treatment; FU = follow-up; ITT = intention to treat; OB = observation; RT = re-treatment; TT = transition-treatment.

Figure 2

Proportions of patients with a PGA rating of “good”, “excellent” or “cleared” by visit at (a) Week 12, after FT period (ITT population) and (b) Week 20, after CT period. Of the CT ITT population, 630 patients had responded during the FT period (FT responders), whereas the remaining 58 patients were nonresponders who had continued to receive efalizumab during the CT period. CT = continuous-treatment; FT = first-treatment; ITT = intention to treat; PGA = Physician Global Assessment.

Figure 3

Proportions of patients with PASI 50, PASI 75 and PASI 90 responses during the FT and CT periods (a) by visit for the ITT population during the FT period and (b) at Week 20 after the CT period. Of the CT ITT population, 630 patients had responded during the FT period (FT responders), whereas the remaining 58 patients were nonresponders who had continued to receive efalizumab during the CT period. CT = continuous-treatment; FT = first-treatment; ITT = intention to treat; PASI = Psoriasis Area and Severity Index.

Figure 4

Proportions of patients with a PGA rating of “good”, “excellent” or “cleared” by visit after (a) re-treatment with efalizumab (RT period*; ITT population, N = 113) or (b) transition to an alternative anti-psoriasis agent (TT period†; ITT population, N = 68). *Patients had completed the FT period and responded but opted to enter the OB period rather than continue treatment with efalizumab; efalizumab treatment was restarted when their psoriasis began to worsen during the OB period. †Patients had completed the FT period but had not responded and received treatment with another approved anti-psoriasis medication. FT = first-treatment; ITT = intention to treat; OB = observation; PGA = Physician Global Assessment; RT = re-treatment; TT = transition-treatment.