A Phase IV study presented as a poster at the American Academy of Dermatology meeting this year in Washington, D.C., supported findings of earlier trials indicating that efalizumab (Raptiva), a humanized anti-CD11a antibody, is safe and effective for the treatment of adult patients with chronic moderate to severe plaque psoriasis on the hands and feet.
This was a blinded, placebo-controlled Phase IV trial involving 80 patients; 46.2% of patients achieved the primary endpoint at 12 weeks, as compared to 17.9% for placebo.
Craig Leonardi, M.D., Professor of Dermatology at St. Louis University, was among 12 investigators, including the five other poster authors, who participated in this multi-center, randomized, placebo-controlled Phase IV trial.
Dr. Leonardi, who also maintains a private practice in St. Louis, suggests that the high rate of “success” in this trial, defined as reaching the primary endpoint of clearance to the point of mild (Table 1), may not be as significant as findings in the secondary analysis showing that this improvement was in fact profound in the nearly one-third of patients whose moderate to severe disease improved to the point of being clear or almost clear (Table 2).
“One of the problems with the primary endpoints is that if you move from a 3 (moderate) to a 2 (mild), that’s considered success. The primary endpoint here netted 46.2% success, but in the more stringent analysis, it was 32.7%. Conceptually, that’s the difference between Psoriasis Area and Severity Index (PASI) 50 and PASI 75 success used in our plaque psoriasis trials.
Hand And Foot Psoriasis Challenges
Dr. Leonardi discussed the special challenges for patients with hand and foot psoriasis and the resistance of this form of the disease to treatment.
“The impact on patients is two-fold. Not only does it interfere with activities of daily life — including using hands for common household chores and walking with the pain that comes with cracking and bleeding feet — it has an enormous impact on these patients’ ability to function in the workplace. Actions we take for granted, such as shaking hands and moving from place to place in an office, can be physically and emotionally devastating to these patients.”
Tough to Treat
Dr. Leonardi explains, too, that neither the behavior nor response to treatment of psoriasis involving the palms and soles conforms to psoriasis found on other areas of the body.
“It’s tough to treat. We don’t have any uniformly successful therapies for hand and foot psoriasis, so doctors tend to reach for many different treatments — some in combination — trying to make something happen for patients.”
In fact, he notes, many patients who ultimately participated in the trial had already undergone aggressive therapies, including hand and foot PUVA therapy, methotrexate, and systemic corticosteroids. Fourteen patients, including 11 in the treatment group and three in the placebo group, had been treated with biologics such as adalimumab (Humira), alefacept (Amevive) and etanercept (Enbrel) before entering the trial for which patients were selected on the basis of disease severity without consideration of previous treatment failures. Although, he adds, patients responsive to other therapies would be unlikely to participate in clinical trials.
Trial Genesis
Dr. Leonardi recalls how Raptiva’s manufacturer, Genentech, decided to sponsor this study targeting hand and foot psoriasis for which no rigorous trials had previously been conducted.
“Genentech had an advisory board meeting inviting physicians to bring in their interesting cases. Because so many brought cases in which hand and foot psoriasis responded well to Raptiva, Genentech decided to conduct a formal study to prove the drug works.”
Study Design and Methods
This randomized, double-blind, placebo- controlled Phase IV study was designed to evaluate the safety and efficacy of subcutaneous (SC) efalizumab in patients with chronic moderate to severe plaque psoriasis (with or without pustules) involving the hands and/or feet. Patients in this study must have had no previous exposure to efalizumab.
The study enrolled a total of 80 patients, randomized 2:1 to receive 12 weeks of either SC efalizumab or SC placebo equivalent, and consisted of a screening period, a treatment period (day 0 to day 84), and an observation period (day 85 to day 112).
The study drug (efalizumab or placebo equivalent) was administered once per week. Patients received a conditioning dose of SC study drug (0.7 mg/kg) followed by 11 doses at 1 mg/kg. After day 84, all patients were transitioned to another treatment (including commercial efalizumab) at the investigator’s discretion.
The primary efficacy outcome measure was the proportion of patients who achieved a Physician’s Global Assessment (PGA) rating of clear (0), almost clear (1), or mild (2) at day 84.
Efficacy Finding
Significantly more patients in the efalizumab arm achieved a PGA rating of clear (0), almost clear (1), or mild (2) at day 84 compared with patients in the placebo arm (46.2% vs. 17.9%). (See Table 1.) Likewise, at day 84, significantly more patients in the efalizumab arm achieved a PGA rating of clear (0) or almost clear (1) compared with patients in the placebo arm (32.7% vs. 7.1%). (See Table 2.)
Safety Findings
The rate of adverse events was similar between the two arms. (See Table 3 below.) Two patients experienced a severe adverse event of psoriasis — one patient receiving placebo experienced an erythrodermic flare of psoriasis, another receiving efalizumab experienced a palmoplantar-pustular flare.
Validity of Findings
Dr. Leonardi believes trials of this type are invaluable in supporting the manufacturer’s product claims.
“This is not just a case report. It’s a multi-center, blinded placebo-controlled trial. I think dermatology ought to start demanding more of these trials from the pharmaceutical industry.”
Leonardi C, Sofen H, Krell J, Caro I, Compton P, Sobell JM. Phase IV Study to Evaluate the Safety and Efficacy of Efalizumab for treatment of Hand and Foot Plaque Psoriasis. Poster presented at American Academy of Dermatology meeting in Washington, D.C., February 2007.
A Phase IV study presented as a poster at the American Academy of Dermatology meeting this year in Washington, D.C., supported findings of earlier trials indicating that efalizumab (Raptiva), a humanized anti-CD11a antibody, is safe and effective for the treatment of adult patients with chronic moderate to severe plaque psoriasis on the hands and feet.
This was a blinded, placebo-controlled Phase IV trial involving 80 patients; 46.2% of patients achieved the primary endpoint at 12 weeks, as compared to 17.9% for placebo.
Craig Leonardi, M.D., Professor of Dermatology at St. Louis University, was among 12 investigators, including the five other poster authors, who participated in this multi-center, randomized, placebo-controlled Phase IV trial.
Dr. Leonardi, who also maintains a private practice in St. Louis, suggests that the high rate of “success” in this trial, defined as reaching the primary endpoint of clearance to the point of mild (Table 1), may not be as significant as findings in the secondary analysis showing that this improvement was in fact profound in the nearly one-third of patients whose moderate to severe disease improved to the point of being clear or almost clear (Table 2).
“One of the problems with the primary endpoints is that if you move from a 3 (moderate) to a 2 (mild), that’s considered success. The primary endpoint here netted 46.2% success, but in the more stringent analysis, it was 32.7%. Conceptually, that’s the difference between Psoriasis Area and Severity Index (PASI) 50 and PASI 75 success used in our plaque psoriasis trials.
Hand And Foot Psoriasis Challenges
Dr. Leonardi discussed the special challenges for patients with hand and foot psoriasis and the resistance of this form of the disease to treatment.
“The impact on patients is two-fold. Not only does it interfere with activities of daily life — including using hands for common household chores and walking with the pain that comes with cracking and bleeding feet — it has an enormous impact on these patients’ ability to function in the workplace. Actions we take for granted, such as shaking hands and moving from place to place in an office, can be physically and emotionally devastating to these patients.”
Tough to Treat
Dr. Leonardi explains, too, that neither the behavior nor response to treatment of psoriasis involving the palms and soles conforms to psoriasis found on other areas of the body.
“It’s tough to treat. We don’t have any uniformly successful therapies for hand and foot psoriasis, so doctors tend to reach for many different treatments — some in combination — trying to make something happen for patients.”
In fact, he notes, many patients who ultimately participated in the trial had already undergone aggressive therapies, including hand and foot PUVA therapy, methotrexate, and systemic corticosteroids. Fourteen patients, including 11 in the treatment group and three in the placebo group, had been treated with biologics such as adalimumab (Humira), alefacept (Amevive) and etanercept (Enbrel) before entering the trial for which patients were selected on the basis of disease severity without consideration of previous treatment failures. Although, he adds, patients responsive to other therapies would be unlikely to participate in clinical trials.
Trial Genesis
Dr. Leonardi recalls how Raptiva’s manufacturer, Genentech, decided to sponsor this study targeting hand and foot psoriasis for which no rigorous trials had previously been conducted.
“Genentech had an advisory board meeting inviting physicians to bring in their interesting cases. Because so many brought cases in which hand and foot psoriasis responded well to Raptiva, Genentech decided to conduct a formal study to prove the drug works.”
Study Design and Methods
This randomized, double-blind, placebo- controlled Phase IV study was designed to evaluate the safety and efficacy of subcutaneous (SC) efalizumab in patients with chronic moderate to severe plaque psoriasis (with or without pustules) involving the hands and/or feet. Patients in this study must have had no previous exposure to efalizumab.
The study enrolled a total of 80 patients, randomized 2:1 to receive 12 weeks of either SC efalizumab or SC placebo equivalent, and consisted of a screening period, a treatment period (day 0 to day 84), and an observation period (day 85 to day 112).
The study drug (efalizumab or placebo equivalent) was administered once per week. Patients received a conditioning dose of SC study drug (0.7 mg/kg) followed by 11 doses at 1 mg/kg. After day 84, all patients were transitioned to another treatment (including commercial efalizumab) at the investigator’s discretion.
The primary efficacy outcome measure was the proportion of patients who achieved a Physician’s Global Assessment (PGA) rating of clear (0), almost clear (1), or mild (2) at day 84.
Efficacy Finding
Significantly more patients in the efalizumab arm achieved a PGA rating of clear (0), almost clear (1), or mild (2) at day 84 compared with patients in the placebo arm (46.2% vs. 17.9%). (See Table 1.) Likewise, at day 84, significantly more patients in the efalizumab arm achieved a PGA rating of clear (0) or almost clear (1) compared with patients in the placebo arm (32.7% vs. 7.1%). (See Table 2.)
Safety Findings
The rate of adverse events was similar between the two arms. (See Table 3 below.) Two patients experienced a severe adverse event of psoriasis — one patient receiving placebo experienced an erythrodermic flare of psoriasis, another receiving efalizumab experienced a palmoplantar-pustular flare.
Validity of Findings
Dr. Leonardi believes trials of this type are invaluable in supporting the manufacturer’s product claims.
“This is not just a case report. It’s a multi-center, blinded placebo-controlled trial. I think dermatology ought to start demanding more of these trials from the pharmaceutical industry.”
Leonardi C, Sofen H, Krell J, Caro I, Compton P, Sobell JM. Phase IV Study to Evaluate the Safety and Efficacy of Efalizumab for treatment of Hand and Foot Plaque Psoriasis. Poster presented at American Academy of Dermatology meeting in Washington, D.C., February 2007.
A Phase IV study presented as a poster at the American Academy of Dermatology meeting this year in Washington, D.C., supported findings of earlier trials indicating that efalizumab (Raptiva), a humanized anti-CD11a antibody, is safe and effective for the treatment of adult patients with chronic moderate to severe plaque psoriasis on the hands and feet.
This was a blinded, placebo-controlled Phase IV trial involving 80 patients; 46.2% of patients achieved the primary endpoint at 12 weeks, as compared to 17.9% for placebo.
Craig Leonardi, M.D., Professor of Dermatology at St. Louis University, was among 12 investigators, including the five other poster authors, who participated in this multi-center, randomized, placebo-controlled Phase IV trial.
Dr. Leonardi, who also maintains a private practice in St. Louis, suggests that the high rate of “success” in this trial, defined as reaching the primary endpoint of clearance to the point of mild (Table 1), may not be as significant as findings in the secondary analysis showing that this improvement was in fact profound in the nearly one-third of patients whose moderate to severe disease improved to the point of being clear or almost clear (Table 2).
“One of the problems with the primary endpoints is that if you move from a 3 (moderate) to a 2 (mild), that’s considered success. The primary endpoint here netted 46.2% success, but in the more stringent analysis, it was 32.7%. Conceptually, that’s the difference between Psoriasis Area and Severity Index (PASI) 50 and PASI 75 success used in our plaque psoriasis trials.
Hand And Foot Psoriasis Challenges
Dr. Leonardi discussed the special challenges for patients with hand and foot psoriasis and the resistance of this form of the disease to treatment.
“The impact on patients is two-fold. Not only does it interfere with activities of daily life — including using hands for common household chores and walking with the pain that comes with cracking and bleeding feet — it has an enormous impact on these patients’ ability to function in the workplace. Actions we take for granted, such as shaking hands and moving from place to place in an office, can be physically and emotionally devastating to these patients.”
Tough to Treat
Dr. Leonardi explains, too, that neither the behavior nor response to treatment of psoriasis involving the palms and soles conforms to psoriasis found on other areas of the body.
“It’s tough to treat. We don’t have any uniformly successful therapies for hand and foot psoriasis, so doctors tend to reach for many different treatments — some in combination — trying to make something happen for patients.”
In fact, he notes, many patients who ultimately participated in the trial had already undergone aggressive therapies, including hand and foot PUVA therapy, methotrexate, and systemic corticosteroids. Fourteen patients, including 11 in the treatment group and three in the placebo group, had been treated with biologics such as adalimumab (Humira), alefacept (Amevive) and etanercept (Enbrel) before entering the trial for which patients were selected on the basis of disease severity without consideration of previous treatment failures. Although, he adds, patients responsive to other therapies would be unlikely to participate in clinical trials.
Trial Genesis
Dr. Leonardi recalls how Raptiva’s manufacturer, Genentech, decided to sponsor this study targeting hand and foot psoriasis for which no rigorous trials had previously been conducted.
“Genentech had an advisory board meeting inviting physicians to bring in their interesting cases. Because so many brought cases in which hand and foot psoriasis responded well to Raptiva, Genentech decided to conduct a formal study to prove the drug works.”
Study Design and Methods
This randomized, double-blind, placebo- controlled Phase IV study was designed to evaluate the safety and efficacy of subcutaneous (SC) efalizumab in patients with chronic moderate to severe plaque psoriasis (with or without pustules) involving the hands and/or feet. Patients in this study must have had no previous exposure to efalizumab.
The study enrolled a total of 80 patients, randomized 2:1 to receive 12 weeks of either SC efalizumab or SC placebo equivalent, and consisted of a screening period, a treatment period (day 0 to day 84), and an observation period (day 85 to day 112).
The study drug (efalizumab or placebo equivalent) was administered once per week. Patients received a conditioning dose of SC study drug (0.7 mg/kg) followed by 11 doses at 1 mg/kg. After day 84, all patients were transitioned to another treatment (including commercial efalizumab) at the investigator’s discretion.
The primary efficacy outcome measure was the proportion of patients who achieved a Physician’s Global Assessment (PGA) rating of clear (0), almost clear (1), or mild (2) at day 84.
Efficacy Finding
Significantly more patients in the efalizumab arm achieved a PGA rating of clear (0), almost clear (1), or mild (2) at day 84 compared with patients in the placebo arm (46.2% vs. 17.9%). (See Table 1.) Likewise, at day 84, significantly more patients in the efalizumab arm achieved a PGA rating of clear (0) or almost clear (1) compared with patients in the placebo arm (32.7% vs. 7.1%). (See Table 2.)
Safety Findings
The rate of adverse events was similar between the two arms. (See Table 3 below.) Two patients experienced a severe adverse event of psoriasis — one patient receiving placebo experienced an erythrodermic flare of psoriasis, another receiving efalizumab experienced a palmoplantar-pustular flare.
Validity of Findings
Dr. Leonardi believes trials of this type are invaluable in supporting the manufacturer’s product claims.
“This is not just a case report. It’s a multi-center, blinded placebo-controlled trial. I think dermatology ought to start demanding more of these trials from the pharmaceutical industry.”
Leonardi C, Sofen H, Krell J, Caro I, Compton P, Sobell JM. Phase IV Study to Evaluate the Safety and Efficacy of Efalizumab for treatment of Hand and Foot Plaque Psoriasis. Poster presented at American Academy of Dermatology meeting in Washington, D.C., February 2007.
