Adalimumab Interruption Leads to Poor Retreatment Response

PARIS — When treatment with adalimumab for moderate to severe psoriasis is interrupted, patients who lost adequate response to initial treatment have a poorer response when treatment is restarted, according to the results of an open-label extension of a phase III study.

"Among patients who were discontinued from adalimumab therapy, those who lost adequate response had poorer responses to subsequent retreatment, compared with those who had not lost adequate response," wrote Dr. Kim A. Pap and his colleagues in a poster presented at the annual congress of the European Academy of Dermatology and Venereology.

The open-label extension was part of the Randomized Controlled Evaluation of Adalimumab Every Other Week Dosing in Moderate to Severe Psoriasis Trial (REVEAL), conducted in the United States and Canada. Patients enrolled in the REVEAL trial had to have an affected body surface area of at least 10%, a Psoriasis Area and Severity Index (PASI) score of at least 12, and a Physician's Global Assessment of at least "moderate." They also could not have previously used anti-tumor necrosis factor therapy.

The trial was composed of three treatment periods: a 16-week double-blind period, during which patients were randomized 2:1 to receive 80 mg adalimumab at week 0 and 40 mg adalimumab every other week or placebo; an open-label period to assess the maintenance of response to 40 mg adalimumab every other week in patients who achieved a PASI 75 or greater by week 16 that lasted until week 33; and another double-blind period in which patients who achieved at least a PASI 75 at weeks 16 and 33 were randomized 1:1 to receive 40 mg adalimumab every other week or placebo, that lasted until week 52 (period C).

Patients who completed the 52-week trial were invited to enroll in an open-label extension study, during which patients received 40 mg adalimumab every other week.

A total of 460 patients—227 who received placebo and 233 who received 40 mg adalimumab in the last period of the REVEAL trial—entered the open-label extension. At the end of period C of the REVEAL study, 28% of those randomized to placebo at week 33 had a loss of adequate response, compared with only 5% of those randomized to adalimumab. Loss of response was defined as less than a 50% improvement in PASI 50 and at least a 6-point increase in PASI score relative to week 33.

At week 12 of the open-label extension, among the patients on adalimumab, more of those who maintained adequate response during period C (83%) achieved a PASI 75 than did those who lost adequate response in period C (45%). Among patients on placebo, more of those who maintained adequate response in period C (81%) achieved PASI 75, compared with 38% of those who lost adequate response in period C, reported Dr. Papp, who is a dermatologist with Probity Medical Research in Waterloo, Ont.

At week 24 of the open-label extension, among patients on adalimumab, more of those who maintained adequate response during period C (83%) achieved a PASI 75 than did those who lost adequate response (55%). Among patients on placebo, more of those who maintained adequate response in period C (84%) achieved PASI 75, compared with 55% of those who lost adequate response.

"Interruption of adalimumab was significantly associated with loss of adequate response," the researchers wrote.

The REVEAL study was sponsored by Abbott Laboratories, manufacturer of adalimumab.

PARIS — When treatment with adalimumab for moderate to severe psoriasis is interrupted, patients who lost adequate response to initial treatment have a poorer response when treatment is restarted, according to the results of an open-label extension of a phase III study.

"Among patients who were discontinued from adalimumab therapy, those who lost adequate response had poorer responses to subsequent retreatment, compared with those who had not lost adequate response," wrote Dr. Kim A. Pap and his colleagues in a poster presented at the annual congress of the European Academy of Dermatology and Venereology.

The open-label extension was part of the Randomized Controlled Evaluation of Adalimumab Every Other Week Dosing in Moderate to Severe Psoriasis Trial (REVEAL), conducted in the United States and Canada. Patients enrolled in the REVEAL trial had to have an affected body surface area of at least 10%, a Psoriasis Area and Severity Index (PASI) score of at least 12, and a Physician's Global Assessment of at least "moderate." They also could not have previously used anti-tumor necrosis factor therapy.

The trial was composed of three treatment periods: a 16-week double-blind period, during which patients were randomized 2:1 to receive 80 mg adalimumab at week 0 and 40 mg adalimumab every other week or placebo; an open-label period to assess the maintenance of response to 40 mg adalimumab every other week in patients who achieved a PASI 75 or greater by week 16 that lasted until week 33; and another double-blind period in which patients who achieved at least a PASI 75 at weeks 16 and 33 were randomized 1:1 to receive 40 mg adalimumab every other week or placebo, that lasted until week 52 (period C).

Patients who completed the 52-week trial were invited to enroll in an open-label extension study, during which patients received 40 mg adalimumab every other week.

A total of 460 patients—227 who received placebo and 233 who received 40 mg adalimumab in the last period of the REVEAL trial—entered the open-label extension. At the end of period C of the REVEAL study, 28% of those randomized to placebo at week 33 had a loss of adequate response, compared with only 5% of those randomized to adalimumab. Loss of response was defined as less than a 50% improvement in PASI 50 and at least a 6-point increase in PASI score relative to week 33.

At week 12 of the open-label extension, among the patients on adalimumab, more of those who maintained adequate response during period C (83%) achieved a PASI 75 than did those who lost adequate response in period C (45%). Among patients on placebo, more of those who maintained adequate response in period C (81%) achieved PASI 75, compared with 38% of those who lost adequate response in period C, reported Dr. Papp, who is a dermatologist with Probity Medical Research in Waterloo, Ont.

At week 24 of the open-label extension, among patients on adalimumab, more of those who maintained adequate response during period C (83%) achieved a PASI 75 than did those who lost adequate response (55%). Among patients on placebo, more of those who maintained adequate response in period C (84%) achieved PASI 75, compared with 55% of those who lost adequate response.

"Interruption of adalimumab was significantly associated with loss of adequate response," the researchers wrote.

The REVEAL study was sponsored by Abbott Laboratories, manufacturer of adalimumab.

PARIS — When treatment with adalimumab for moderate to severe psoriasis is interrupted, patients who lost adequate response to initial treatment have a poorer response when treatment is restarted, according to the results of an open-label extension of a phase III study.

"Among patients who were discontinued from adalimumab therapy, those who lost adequate response had poorer responses to subsequent retreatment, compared with those who had not lost adequate response," wrote Dr. Kim A. Pap and his colleagues in a poster presented at the annual congress of the European Academy of Dermatology and Venereology.

The open-label extension was part of the Randomized Controlled Evaluation of Adalimumab Every Other Week Dosing in Moderate to Severe Psoriasis Trial (REVEAL), conducted in the United States and Canada. Patients enrolled in the REVEAL trial had to have an affected body surface area of at least 10%, a Psoriasis Area and Severity Index (PASI) score of at least 12, and a Physician's Global Assessment of at least "moderate." They also could not have previously used anti-tumor necrosis factor therapy.

The trial was composed of three treatment periods: a 16-week double-blind period, during which patients were randomized 2:1 to receive 80 mg adalimumab at week 0 and 40 mg adalimumab every other week or placebo; an open-label period to assess the maintenance of response to 40 mg adalimumab every other week in patients who achieved a PASI 75 or greater by week 16 that lasted until week 33; and another double-blind period in which patients who achieved at least a PASI 75 at weeks 16 and 33 were randomized 1:1 to receive 40 mg adalimumab every other week or placebo, that lasted until week 52 (period C).

Patients who completed the 52-week trial were invited to enroll in an open-label extension study, during which patients received 40 mg adalimumab every other week.

A total of 460 patients—227 who received placebo and 233 who received 40 mg adalimumab in the last period of the REVEAL trial—entered the open-label extension. At the end of period C of the REVEAL study, 28% of those randomized to placebo at week 33 had a loss of adequate response, compared with only 5% of those randomized to adalimumab. Loss of response was defined as less than a 50% improvement in PASI 50 and at least a 6-point increase in PASI score relative to week 33.

At week 12 of the open-label extension, among the patients on adalimumab, more of those who maintained adequate response during period C (83%) achieved a PASI 75 than did those who lost adequate response in period C (45%). Among patients on placebo, more of those who maintained adequate response in period C (81%) achieved PASI 75, compared with 38% of those who lost adequate response in period C, reported Dr. Papp, who is a dermatologist with Probity Medical Research in Waterloo, Ont.

At week 24 of the open-label extension, among patients on adalimumab, more of those who maintained adequate response during period C (83%) achieved a PASI 75 than did those who lost adequate response (55%). Among patients on placebo, more of those who maintained adequate response in period C (84%) achieved PASI 75, compared with 55% of those who lost adequate response.

"Interruption of adalimumab was significantly associated with loss of adequate response," the researchers wrote.

The REVEAL study was sponsored by Abbott Laboratories, manufacturer of adalimumab.