Tofacitinib found noninferior to etanercept for treating psoriasis

DENVER – Key results from a phase III trial found that an investigational Janus kinase inhibitor was noninferior to a biologic agent for treating psoriasis.

During a late-breaking session at the annual meeting of the American Academy of Dermatology, Dr. Fernando Valenzuela presented findings from a multicenter, double-dummy 12-week comparison of tofacitinib vs. etanercept or placebo for the treatment of patients with moderate to severe psoriasis. Tofacitinib is an investigational Janus kinase inhibitor being developed by Pfizer.

Twice-daily tofacitinib at 5 mg and 10 mg was effective in patients with moderate to severe psoriasis, and the efficacy of twice-daily tofacitinib at 10 mg was similar to twice-weekly etanercept at 50 mg and was superior to placebo.

"Plaque psoriasis is a chronic, immune-mediated systemic disease [that] can lead to major quality of life impairment in its moderate to severe forms," said Dr. Valenzuela of the department of dermatology at the University of Chile Clinical Hospital, Santiago. "The JAK/STAT [Janus kinase/signal transducers and activators of transcription] signaling pathway is implicated in the pathogenesis of chronic immune-mediated diseases including psoriasis. Tofacitinib has previously demonstrated significant efficacy in a placebo-controlled, phase II study in patients with moderate to severe plaque psoriasis."

In the 12-week multicenter trial known as OPT Compare, which was conducted in 23 countries outside of North America, he and his associates assessed the noninferiority/superiority of two doses of oral tofacitinib vs. high-dose etanercept or placebo. To be eligible for the trial, patients had to be at least 18 years of age; have moderate to severe chronic plaque psoriasis; be candidates for systemic therapy or phototherapy; have a Psoriasis Area and Severity Index (PASI) of 12 or greater; have a Physician’s Global Assessment (PGA) of moderate or severe; have psoriasis involvement of 10% or greater body surface area; and had failed to respond, tolerate, or have a contraindication to at least one systemic therapy. Patients previously treated with etanercept or who previously experienced failure to treatment with a tumor necrosis factor therapy were excluded from the trial.

Patients were randomized 3:3:3:1 in the following fashion over a 12-week period: 329 received tofacitinib b.i.d.; 330 received tofacitinib 10 mg b.i.d.; 335 received etanercept 50 mg subcutaneously twice weekly; and 107 received placebo. The coprimary efficacy endpoints were the proportion of patients achieving at least a 75% reduction in PASI score at week 12 from baseline and a PGA score of "clear" or "almost clear" at week 12. The researchers used a fixed sequence procedure to assess noninferiority/superiority sequentially in order to control overall type 1 error. The mean age of patients was 44 years and about 82% of patients had moderate disease.

Dr. Valenzuela reported that at 12 weeks, 39.5%, 63.6%, 58.8%, and 5.6% of patients achieved PASI 75 responses and 47.1%, 68.2%, 66.3%, and 15.0% achieved PGA responses with tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, etanercept 50 mg twice weekly, and placebo, respectively. Tofacitinib 10 mg twice a day was noninferior to etanercept and superior to placebo (P less than .0001), but tofacitinib 5 mg twice a day did not meet the noninferiority criterion vs. etanercept.

Over 12 weeks, the safety and tolerability of either dose of tofacitinib was similar to that of etanercept. "The most frequent adverse events were infections, most commonly nasopharyngitis and upper respiratory tract infection," Dr. Valenzuela said. "Hypercholesterolemia and dyslipidemia were more common in tofacitinib recipients, as was an increase in creatine phosphokinase*." Injection site reactions were most frequent among etanercept recipients.

The study was sponsored by Pfizer. Dr. Valenzuela disclosed that he has been a principal investigator, member of a scientific advisory board, or speaker for Pfizer, Janssen, Eli Lilly, Merck, and Novartis.

[email protected]

*Correction, 3/27/2014: An earlier version of this article misstated the term creatine phosphokinase.

DENVER – Key results from a phase III trial found that an investigational Janus kinase inhibitor was noninferior to a biologic agent for treating psoriasis.

During a late-breaking session at the annual meeting of the American Academy of Dermatology, Dr. Fernando Valenzuela presented findings from a multicenter, double-dummy 12-week comparison of tofacitinib vs. etanercept or placebo for the treatment of patients with moderate to severe psoriasis. Tofacitinib is an investigational Janus kinase inhibitor being developed by Pfizer.

Twice-daily tofacitinib at 5 mg and 10 mg was effective in patients with moderate to severe psoriasis, and the efficacy of twice-daily tofacitinib at 10 mg was similar to twice-weekly etanercept at 50 mg and was superior to placebo.

"Plaque psoriasis is a chronic, immune-mediated systemic disease [that] can lead to major quality of life impairment in its moderate to severe forms," said Dr. Valenzuela of the department of dermatology at the University of Chile Clinical Hospital, Santiago. "The JAK/STAT [Janus kinase/signal transducers and activators of transcription] signaling pathway is implicated in the pathogenesis of chronic immune-mediated diseases including psoriasis. Tofacitinib has previously demonstrated significant efficacy in a placebo-controlled, phase II study in patients with moderate to severe plaque psoriasis."

In the 12-week multicenter trial known as OPT Compare, which was conducted in 23 countries outside of North America, he and his associates assessed the noninferiority/superiority of two doses of oral tofacitinib vs. high-dose etanercept or placebo. To be eligible for the trial, patients had to be at least 18 years of age; have moderate to severe chronic plaque psoriasis; be candidates for systemic therapy or phototherapy; have a Psoriasis Area and Severity Index (PASI) of 12 or greater; have a Physician’s Global Assessment (PGA) of moderate or severe; have psoriasis involvement of 10% or greater body surface area; and had failed to respond, tolerate, or have a contraindication to at least one systemic therapy. Patients previously treated with etanercept or who previously experienced failure to treatment with a tumor necrosis factor therapy were excluded from the trial.

Patients were randomized 3:3:3:1 in the following fashion over a 12-week period: 329 received tofacitinib b.i.d.; 330 received tofacitinib 10 mg b.i.d.; 335 received etanercept 50 mg subcutaneously twice weekly; and 107 received placebo. The coprimary efficacy endpoints were the proportion of patients achieving at least a 75% reduction in PASI score at week 12 from baseline and a PGA score of "clear" or "almost clear" at week 12. The researchers used a fixed sequence procedure to assess noninferiority/superiority sequentially in order to control overall type 1 error. The mean age of patients was 44 years and about 82% of patients had moderate disease.

Dr. Valenzuela reported that at 12 weeks, 39.5%, 63.6%, 58.8%, and 5.6% of patients achieved PASI 75 responses and 47.1%, 68.2%, 66.3%, and 15.0% achieved PGA responses with tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, etanercept 50 mg twice weekly, and placebo, respectively. Tofacitinib 10 mg twice a day was noninferior to etanercept and superior to placebo (P less than .0001), but tofacitinib 5 mg twice a day did not meet the noninferiority criterion vs. etanercept.

Over 12 weeks, the safety and tolerability of either dose of tofacitinib was similar to that of etanercept. "The most frequent adverse events were infections, most commonly nasopharyngitis and upper respiratory tract infection," Dr. Valenzuela said. "Hypercholesterolemia and dyslipidemia were more common in tofacitinib recipients, as was an increase in creatine phosphokinase*." Injection site reactions were most frequent among etanercept recipients.

The study was sponsored by Pfizer. Dr. Valenzuela disclosed that he has been a principal investigator, member of a scientific advisory board, or speaker for Pfizer, Janssen, Eli Lilly, Merck, and Novartis.

[email protected]

*Correction, 3/27/2014: An earlier version of this article misstated the term creatine phosphokinase.

DENVER – Key results from a phase III trial found that an investigational Janus kinase inhibitor was noninferior to a biologic agent for treating psoriasis.

During a late-breaking session at the annual meeting of the American Academy of Dermatology, Dr. Fernando Valenzuela presented findings from a multicenter, double-dummy 12-week comparison of tofacitinib vs. etanercept or placebo for the treatment of patients with moderate to severe psoriasis. Tofacitinib is an investigational Janus kinase inhibitor being developed by Pfizer.

Twice-daily tofacitinib at 5 mg and 10 mg was effective in patients with moderate to severe psoriasis, and the efficacy of twice-daily tofacitinib at 10 mg was similar to twice-weekly etanercept at 50 mg and was superior to placebo.

"Plaque psoriasis is a chronic, immune-mediated systemic disease [that] can lead to major quality of life impairment in its moderate to severe forms," said Dr. Valenzuela of the department of dermatology at the University of Chile Clinical Hospital, Santiago. "The JAK/STAT [Janus kinase/signal transducers and activators of transcription] signaling pathway is implicated in the pathogenesis of chronic immune-mediated diseases including psoriasis. Tofacitinib has previously demonstrated significant efficacy in a placebo-controlled, phase II study in patients with moderate to severe plaque psoriasis."

In the 12-week multicenter trial known as OPT Compare, which was conducted in 23 countries outside of North America, he and his associates assessed the noninferiority/superiority of two doses of oral tofacitinib vs. high-dose etanercept or placebo. To be eligible for the trial, patients had to be at least 18 years of age; have moderate to severe chronic plaque psoriasis; be candidates for systemic therapy or phototherapy; have a Psoriasis Area and Severity Index (PASI) of 12 or greater; have a Physician’s Global Assessment (PGA) of moderate or severe; have psoriasis involvement of 10% or greater body surface area; and had failed to respond, tolerate, or have a contraindication to at least one systemic therapy. Patients previously treated with etanercept or who previously experienced failure to treatment with a tumor necrosis factor therapy were excluded from the trial.

Patients were randomized 3:3:3:1 in the following fashion over a 12-week period: 329 received tofacitinib b.i.d.; 330 received tofacitinib 10 mg b.i.d.; 335 received etanercept 50 mg subcutaneously twice weekly; and 107 received placebo. The coprimary efficacy endpoints were the proportion of patients achieving at least a 75% reduction in PASI score at week 12 from baseline and a PGA score of "clear" or "almost clear" at week 12. The researchers used a fixed sequence procedure to assess noninferiority/superiority sequentially in order to control overall type 1 error. The mean age of patients was 44 years and about 82% of patients had moderate disease.

Dr. Valenzuela reported that at 12 weeks, 39.5%, 63.6%, 58.8%, and 5.6% of patients achieved PASI 75 responses and 47.1%, 68.2%, 66.3%, and 15.0% achieved PGA responses with tofacitinib 5 mg twice daily, tofacitinib 10 mg twice daily, etanercept 50 mg twice weekly, and placebo, respectively. Tofacitinib 10 mg twice a day was noninferior to etanercept and superior to placebo (P less than .0001), but tofacitinib 5 mg twice a day did not meet the noninferiority criterion vs. etanercept.

Over 12 weeks, the safety and tolerability of either dose of tofacitinib was similar to that of etanercept. "The most frequent adverse events were infections, most commonly nasopharyngitis and upper respiratory tract infection," Dr. Valenzuela said. "Hypercholesterolemia and dyslipidemia were more common in tofacitinib recipients, as was an increase in creatine phosphokinase*." Injection site reactions were most frequent among etanercept recipients.

The study was sponsored by Pfizer. Dr. Valenzuela disclosed that he has been a principal investigator, member of a scientific advisory board, or speaker for Pfizer, Janssen, Eli Lilly, Merck, and Novartis.

[email protected]

*Correction, 3/27/2014: An earlier version of this article misstated the term creatine phosphokinase.