Interrupting Biologic Therapy for Psoriasis: What to Expect

GOTHENBURG, SWEDEN – Biologic therapies have brought dermatologists an unprecedented ability to control moderate to severe psoriasis. But with these treatment victories have come questions about how treatment interruptions affect long-term response, according to Dr. Richard Langley.

New evidence indicates most psoriasis patients who are responding well to adalimumab (Humira) and then undergo a treatment interruption or drug holiday will regain nearly the same favorable level of response upon treatment resumption. But a substantial minority – roughly one-third of those randomized to a treatment interruption in the 3-year open-label extension of the REVEAL trial – will not be able to recapture their prior high level of response, he said at a satellite symposium held during the annual congress of the European Academy of Dermatology and Venereology

The good news, he added, is that this high-risk subgroup can be identified early in the course of their treatment interruption, in time for corrective action to be taken.

"The take-home message is that in patients who have an early loss of response during the interruption, particularly those who drop to less than Psoriasis Area and Severity Index [PASI] 50, these are people we should think about getting back on treatment. Many of these patients are getting an inferior result compared with what they’d have on continuous therapy or early retreatment," according to Dr. Langley, professor of medicine and director of research in the division of dermatology at Dalhousie University, Halifax, N.S.

The phase III REVEAL (Randomized Controlled Evaluation of Adalimumab Every Other Week Dosing in Moderate to Severe Psoriasis Trial) was a placebo-controlled, 52-week randomized trial in which 490 of the 814 patients randomized to adalimumab at baseline achieved at least a 75% improvement (PASI 75) at weeks 16 and 33, compared with baseline. These good responders were then rerandomized to 19 weeks of continued adalimumab or treatment interruption via placebo. After this 19-week interval, patients could receive an additional 2 years of adalimumab at 40 mg every 2 weeks in a long-term, open-label extension study.

In a new REVEAL analysis presented for the first time at the satellite symposium sponsored by Abbott, Dr. Langley reported that of 227 patients randomized to the 19-week treatment interruption, 45% were still at PASI 75-100 at the start of retreatment, 31% had dropped below PASI 50, and 24% were in between. The mean disease severity scores in these three groups at the start of retreatment were PASI 88, PASI 32, and PASI 64, respectively. Over the next 2 years of open-label retreatment, the patients who started retreatment with less than a PASI 50 showed an inferior response, compared with the other two groups. They climbed to a peak response of PASI 66 at week 24 of retreatment and finished at a mean PASI 58 at week 108.

In contrast, patients who were PASI 75-100 at the start of retreatment, compared with enrollment, peaked at a mean PASI 94 at week 12 of retreatment, finishing at PASI 86 at week 108. Those with PASI 50-74 when retreatment commenced had a peak PASI 79 at week 12 before finishing the extension study with a mean PASI 81, according to Dr. Langley.

Similar findings have been seen in other treatment interruption studies involving etanercept and infliximab: Retreatment of patients who were good responders prior to the interruption restored efficacy in most but not all patients, he continued.

Dr. Langley stressed that in his view the preferred strategy is continuous treatment of good responders to any given biologic agent. He said he is opposed to the idea of drug holidays in patients who have cleared because in a substantial number of cases, their disease will return and their quality of life will plummet.

"Is that truly the sort of holiday we want to take?" he asked. "You can start and stop, and start and stop, but ultimately you are losing control of some of these patients."

Of course, there are circumstances when a treatment interruption is necessary. This happens fairly frequently. Among the situations warranting a temporary halt to biologic therapy are pregnancy, major surgery, live virus vaccination, clinically significant infection, or an adverse event whose cause is uncertain.

Dr. Langley disclosed that he is on the speakers bureau for Abbott Laboratories and has financial relationships with numerous other pharmaceutical companies with an interest in psoriasis therapies.

GOTHENBURG, SWEDEN – Biologic therapies have brought dermatologists an unprecedented ability to control moderate to severe psoriasis. But with these treatment victories have come questions about how treatment interruptions affect long-term response, according to Dr. Richard Langley.

New evidence indicates most psoriasis patients who are responding well to adalimumab (Humira) and then undergo a treatment interruption or drug holiday will regain nearly the same favorable level of response upon treatment resumption. But a substantial minority – roughly one-third of those randomized to a treatment interruption in the 3-year open-label extension of the REVEAL trial – will not be able to recapture their prior high level of response, he said at a satellite symposium held during the annual congress of the European Academy of Dermatology and Venereology

The good news, he added, is that this high-risk subgroup can be identified early in the course of their treatment interruption, in time for corrective action to be taken.

"The take-home message is that in patients who have an early loss of response during the interruption, particularly those who drop to less than Psoriasis Area and Severity Index [PASI] 50, these are people we should think about getting back on treatment. Many of these patients are getting an inferior result compared with what they’d have on continuous therapy or early retreatment," according to Dr. Langley, professor of medicine and director of research in the division of dermatology at Dalhousie University, Halifax, N.S.

The phase III REVEAL (Randomized Controlled Evaluation of Adalimumab Every Other Week Dosing in Moderate to Severe Psoriasis Trial) was a placebo-controlled, 52-week randomized trial in which 490 of the 814 patients randomized to adalimumab at baseline achieved at least a 75% improvement (PASI 75) at weeks 16 and 33, compared with baseline. These good responders were then rerandomized to 19 weeks of continued adalimumab or treatment interruption via placebo. After this 19-week interval, patients could receive an additional 2 years of adalimumab at 40 mg every 2 weeks in a long-term, open-label extension study.

In a new REVEAL analysis presented for the first time at the satellite symposium sponsored by Abbott, Dr. Langley reported that of 227 patients randomized to the 19-week treatment interruption, 45% were still at PASI 75-100 at the start of retreatment, 31% had dropped below PASI 50, and 24% were in between. The mean disease severity scores in these three groups at the start of retreatment were PASI 88, PASI 32, and PASI 64, respectively. Over the next 2 years of open-label retreatment, the patients who started retreatment with less than a PASI 50 showed an inferior response, compared with the other two groups. They climbed to a peak response of PASI 66 at week 24 of retreatment and finished at a mean PASI 58 at week 108.

In contrast, patients who were PASI 75-100 at the start of retreatment, compared with enrollment, peaked at a mean PASI 94 at week 12 of retreatment, finishing at PASI 86 at week 108. Those with PASI 50-74 when retreatment commenced had a peak PASI 79 at week 12 before finishing the extension study with a mean PASI 81, according to Dr. Langley.

Similar findings have been seen in other treatment interruption studies involving etanercept and infliximab: Retreatment of patients who were good responders prior to the interruption restored efficacy in most but not all patients, he continued.

Dr. Langley stressed that in his view the preferred strategy is continuous treatment of good responders to any given biologic agent. He said he is opposed to the idea of drug holidays in patients who have cleared because in a substantial number of cases, their disease will return and their quality of life will plummet.

"Is that truly the sort of holiday we want to take?" he asked. "You can start and stop, and start and stop, but ultimately you are losing control of some of these patients."

Of course, there are circumstances when a treatment interruption is necessary. This happens fairly frequently. Among the situations warranting a temporary halt to biologic therapy are pregnancy, major surgery, live virus vaccination, clinically significant infection, or an adverse event whose cause is uncertain.

Dr. Langley disclosed that he is on the speakers bureau for Abbott Laboratories and has financial relationships with numerous other pharmaceutical companies with an interest in psoriasis therapies.

GOTHENBURG, SWEDEN – Biologic therapies have brought dermatologists an unprecedented ability to control moderate to severe psoriasis. But with these treatment victories have come questions about how treatment interruptions affect long-term response, according to Dr. Richard Langley.

New evidence indicates most psoriasis patients who are responding well to adalimumab (Humira) and then undergo a treatment interruption or drug holiday will regain nearly the same favorable level of response upon treatment resumption. But a substantial minority – roughly one-third of those randomized to a treatment interruption in the 3-year open-label extension of the REVEAL trial – will not be able to recapture their prior high level of response, he said at a satellite symposium held during the annual congress of the European Academy of Dermatology and Venereology

The good news, he added, is that this high-risk subgroup can be identified early in the course of their treatment interruption, in time for corrective action to be taken.

"The take-home message is that in patients who have an early loss of response during the interruption, particularly those who drop to less than Psoriasis Area and Severity Index [PASI] 50, these are people we should think about getting back on treatment. Many of these patients are getting an inferior result compared with what they’d have on continuous therapy or early retreatment," according to Dr. Langley, professor of medicine and director of research in the division of dermatology at Dalhousie University, Halifax, N.S.

The phase III REVEAL (Randomized Controlled Evaluation of Adalimumab Every Other Week Dosing in Moderate to Severe Psoriasis Trial) was a placebo-controlled, 52-week randomized trial in which 490 of the 814 patients randomized to adalimumab at baseline achieved at least a 75% improvement (PASI 75) at weeks 16 and 33, compared with baseline. These good responders were then rerandomized to 19 weeks of continued adalimumab or treatment interruption via placebo. After this 19-week interval, patients could receive an additional 2 years of adalimumab at 40 mg every 2 weeks in a long-term, open-label extension study.

In a new REVEAL analysis presented for the first time at the satellite symposium sponsored by Abbott, Dr. Langley reported that of 227 patients randomized to the 19-week treatment interruption, 45% were still at PASI 75-100 at the start of retreatment, 31% had dropped below PASI 50, and 24% were in between. The mean disease severity scores in these three groups at the start of retreatment were PASI 88, PASI 32, and PASI 64, respectively. Over the next 2 years of open-label retreatment, the patients who started retreatment with less than a PASI 50 showed an inferior response, compared with the other two groups. They climbed to a peak response of PASI 66 at week 24 of retreatment and finished at a mean PASI 58 at week 108.

In contrast, patients who were PASI 75-100 at the start of retreatment, compared with enrollment, peaked at a mean PASI 94 at week 12 of retreatment, finishing at PASI 86 at week 108. Those with PASI 50-74 when retreatment commenced had a peak PASI 79 at week 12 before finishing the extension study with a mean PASI 81, according to Dr. Langley.

Similar findings have been seen in other treatment interruption studies involving etanercept and infliximab: Retreatment of patients who were good responders prior to the interruption restored efficacy in most but not all patients, he continued.

Dr. Langley stressed that in his view the preferred strategy is continuous treatment of good responders to any given biologic agent. He said he is opposed to the idea of drug holidays in patients who have cleared because in a substantial number of cases, their disease will return and their quality of life will plummet.

"Is that truly the sort of holiday we want to take?" he asked. "You can start and stop, and start and stop, but ultimately you are losing control of some of these patients."

Of course, there are circumstances when a treatment interruption is necessary. This happens fairly frequently. Among the situations warranting a temporary halt to biologic therapy are pregnancy, major surgery, live virus vaccination, clinically significant infection, or an adverse event whose cause is uncertain.

Dr. Langley disclosed that he is on the speakers bureau for Abbott Laboratories and has financial relationships with numerous other pharmaceutical companies with an interest in psoriasis therapies.