The Whys and How of Stopping Biologics

The vast majority of medical talks on biologic therapy for psoriasis focus on starting and maintaining the medications. Stopping biologics is a seldom-discussed topic, yet one that physicians often need to address.

"We’ve all got patients who are on biologic therapy who are completely clear of their psoriasis, and you’re constantly wondering, ‘Should I stop the biologic? Do they need to have that treatment anymore? Can I reduce the dosing frequency?’ The simplest answer is that in most cases, it’s probably not a good idea to stop unless there’s a good reason for doing so. It has been shown in most of the big clinical trials that if you stop therapy, the psoriasis will relapse at some point," Dr. Christopher Griffiths said at the annual congress of the European Academy of Dermatology and Venereology.

"With long-term therapy beyond 6-12 months, can biologics be stopped or produce remission? In most cases, no. And there’s no biomarker for disease activity as of yet to guide us," added Dr. Griffiths, professor of dermatology and associate dean for research at the University of Manchester (England).

Compelling reasons to stop biologic therapy include failure to achieve or maintain significant clinical improvement, serious adverse events, impending elective major surgery, certain vaccinations, and pregnancy. Dr. Griffiths highlighted the following points:

• Lack of Effectiveness. Today’s biologics are not curative. In a recent French report, only 31 of 86 psoriasis patients (36%) who started on etanercept (Enbrel), infliximab (Remicade), or efalizumab were still on the same biologic agent 24 months later (J. Dermatol. Treat. 2011;22:151-2). Similarly, the Danish national psoriasis database experience has been that roughly 40% of patients started on etanercept or adalimumab (Humira) were still on the medication 4 years later, as were 70% of those who started on infliximab (Br. J. Dermatol. 2011;164:1091-6).

The good news, Dr. Griffiths continued, is that lack of effectiveness for anti–tumor necrosis factor agents is not a class effect. He and his coinvestigators have reported that 21 of 31 psoriasis patients who switched to adalimumab from another anti-TNF biologic for lack of efficacy met the NICE (U.K. National Institute for Health and Clinical Excellence) criteria for adalimumab treatment continuation at 16 weeks (Br. J. Dermatol. 2010;163:859-62).

"Each anti-TNF drug is different, so if you fail one it doesn’t mean you’re going to fail another. That’s a very important point, and a very strong argument in your favor when dealing with payers. And it’s an observation that can only come from real-life data from a cohort study; you’re not going to get that information from clinical trials," the dermatologist explained.

The NICE criteria for continuation of biologic therapy bring an element of strict objectivity to treatment decision making in a rationed health care system. For British psoriasis patients to continue on a given biologic agent, they have to demonstrate a PASI 75 response (that is, a 75% improvement over the baseline Psoriasis Area and Severity Index score) at 16 weeks, or a PASI 50 response plus a 5-point drop in the Dermatology Life Quality Index (DLQI).

When physicians switch biologics, Dr. Griffiths recommends that they skip a lengthy washout period because of the associated risk of a severe, hard-to-control flare. His practice is to stop one and start another.

• Major Elective Surgery. There is a dearth of data on stopping biologics in psoriasis patients who plan to undergo elective surgery. The best practice for now, in Dr. Griffiths’ view, is to follow the British Society for Rheumatology guidance, which is based on an extensive biologics register the group maintains for rheumatoid arthritis.

The rheumatologists’ advice is to halt effective biologic therapy only for truly major surgery, and to stop anti-TNF drugs more than four half-lives before the operation. That’s 2-3 weeks beforehand for etanercept, 6-8 weeks for adalimumab, and 4-6 weeks for infliximab. There are no firm data for ustekinumab (Stelara) as yet, but experts advise halting it 12 weeks before surgery. Biologic therapy should be resumed as soon as possible postoperatively.

• Pregnancy. Again, a paucity of data exists on biologics for psoriasis in pregnancy. But the data accumulating in the British Society for Rheumatology Biologics Register (BSRBR) is reassuring. Although the rheumatologists recommend that pregnancy be avoided in patients on biologics, the experience to date in pregnant rheumatoid arthritis patients suggests there is little to no risk to the fetus. Breastfeeding should be avoided by women on biologic therapy other than infliximab, which is not excreted in breast milk, Dr. Griffiths continued.

• Vaccinations. British Association of Dermatologists guidelines on the use of biologics for psoriasis (Br. J. Dermatol. 2009;161:987-1019), which Dr. Griffiths coauthored and which will be updated in late 2012, recommend avoiding giving live or attenuated virus vaccines within 2 weeks prior to starting a patient on biologic therapy, or while the patient is on a biologic, or for up to 6 months after the patient stops the biologic. Inactivated virus vaccines are safe for patients on biologic therapy, although the antibody response will be somewhat less robust in a patient on an anti-TNF agent than in other individuals.

"But we advise – as should you – that all patients on biologics should receive influenza and pneumococcal vaccines. It’s just good clinical practice because these patients are by definition in a high-risk category," he said.

• Stopping and Restarting Biologics. It’s well established that etanercept can be used intermittently with good results. That is, a patient might use etanercept to good effect for 6 months, stop it, then restart when relapse occurs, and the agent will still remain effective. The same typically holds true for alefacept (Amevive).

In contrast, infliximab can realistically be used for only a single course of treatment. If a patient goes off the drug and later goes back on it, the chances of regaining a response are very low because of the formation of blocking antibodies.

The picture regarding the intermittent use of adalimumab is less clear. There are documented cases in which this agent hasn’t been effective any longer upon second usage.

There is good new evidence, presented by Dr. Griffiths elsewhere during the congress, that ustekinumab can be restarted after a hiatus with very good results.

Dr. Griffiths disclosed that he serves on the advisory boards for and has received research grants from numerous pharmaceutical companies.

The vast majority of medical talks on biologic therapy for psoriasis focus on starting and maintaining the medications. Stopping biologics is a seldom-discussed topic, yet one that physicians often need to address.

"We’ve all got patients who are on biologic therapy who are completely clear of their psoriasis, and you’re constantly wondering, ‘Should I stop the biologic? Do they need to have that treatment anymore? Can I reduce the dosing frequency?’ The simplest answer is that in most cases, it’s probably not a good idea to stop unless there’s a good reason for doing so. It has been shown in most of the big clinical trials that if you stop therapy, the psoriasis will relapse at some point," Dr. Christopher Griffiths said at the annual congress of the European Academy of Dermatology and Venereology.

"With long-term therapy beyond 6-12 months, can biologics be stopped or produce remission? In most cases, no. And there’s no biomarker for disease activity as of yet to guide us," added Dr. Griffiths, professor of dermatology and associate dean for research at the University of Manchester (England).

Compelling reasons to stop biologic therapy include failure to achieve or maintain significant clinical improvement, serious adverse events, impending elective major surgery, certain vaccinations, and pregnancy. Dr. Griffiths highlighted the following points:

• Lack of Effectiveness. Today’s biologics are not curative. In a recent French report, only 31 of 86 psoriasis patients (36%) who started on etanercept (Enbrel), infliximab (Remicade), or efalizumab were still on the same biologic agent 24 months later (J. Dermatol. Treat. 2011;22:151-2). Similarly, the Danish national psoriasis database experience has been that roughly 40% of patients started on etanercept or adalimumab (Humira) were still on the medication 4 years later, as were 70% of those who started on infliximab (Br. J. Dermatol. 2011;164:1091-6).

The good news, Dr. Griffiths continued, is that lack of effectiveness for anti–tumor necrosis factor agents is not a class effect. He and his coinvestigators have reported that 21 of 31 psoriasis patients who switched to adalimumab from another anti-TNF biologic for lack of efficacy met the NICE (U.K. National Institute for Health and Clinical Excellence) criteria for adalimumab treatment continuation at 16 weeks (Br. J. Dermatol. 2010;163:859-62).

"Each anti-TNF drug is different, so if you fail one it doesn’t mean you’re going to fail another. That’s a very important point, and a very strong argument in your favor when dealing with payers. And it’s an observation that can only come from real-life data from a cohort study; you’re not going to get that information from clinical trials," the dermatologist explained.

The NICE criteria for continuation of biologic therapy bring an element of strict objectivity to treatment decision making in a rationed health care system. For British psoriasis patients to continue on a given biologic agent, they have to demonstrate a PASI 75 response (that is, a 75% improvement over the baseline Psoriasis Area and Severity Index score) at 16 weeks, or a PASI 50 response plus a 5-point drop in the Dermatology Life Quality Index (DLQI).

When physicians switch biologics, Dr. Griffiths recommends that they skip a lengthy washout period because of the associated risk of a severe, hard-to-control flare. His practice is to stop one and start another.

• Major Elective Surgery. There is a dearth of data on stopping biologics in psoriasis patients who plan to undergo elective surgery. The best practice for now, in Dr. Griffiths’ view, is to follow the British Society for Rheumatology guidance, which is based on an extensive biologics register the group maintains for rheumatoid arthritis.

The rheumatologists’ advice is to halt effective biologic therapy only for truly major surgery, and to stop anti-TNF drugs more than four half-lives before the operation. That’s 2-3 weeks beforehand for etanercept, 6-8 weeks for adalimumab, and 4-6 weeks for infliximab. There are no firm data for ustekinumab (Stelara) as yet, but experts advise halting it 12 weeks before surgery. Biologic therapy should be resumed as soon as possible postoperatively.

• Pregnancy. Again, a paucity of data exists on biologics for psoriasis in pregnancy. But the data accumulating in the British Society for Rheumatology Biologics Register (BSRBR) is reassuring. Although the rheumatologists recommend that pregnancy be avoided in patients on biologics, the experience to date in pregnant rheumatoid arthritis patients suggests there is little to no risk to the fetus. Breastfeeding should be avoided by women on biologic therapy other than infliximab, which is not excreted in breast milk, Dr. Griffiths continued.

• Vaccinations. British Association of Dermatologists guidelines on the use of biologics for psoriasis (Br. J. Dermatol. 2009;161:987-1019), which Dr. Griffiths coauthored and which will be updated in late 2012, recommend avoiding giving live or attenuated virus vaccines within 2 weeks prior to starting a patient on biologic therapy, or while the patient is on a biologic, or for up to 6 months after the patient stops the biologic. Inactivated virus vaccines are safe for patients on biologic therapy, although the antibody response will be somewhat less robust in a patient on an anti-TNF agent than in other individuals.

"But we advise – as should you – that all patients on biologics should receive influenza and pneumococcal vaccines. It’s just good clinical practice because these patients are by definition in a high-risk category," he said.

• Stopping and Restarting Biologics. It’s well established that etanercept can be used intermittently with good results. That is, a patient might use etanercept to good effect for 6 months, stop it, then restart when relapse occurs, and the agent will still remain effective. The same typically holds true for alefacept (Amevive).

In contrast, infliximab can realistically be used for only a single course of treatment. If a patient goes off the drug and later goes back on it, the chances of regaining a response are very low because of the formation of blocking antibodies.

The picture regarding the intermittent use of adalimumab is less clear. There are documented cases in which this agent hasn’t been effective any longer upon second usage.

There is good new evidence, presented by Dr. Griffiths elsewhere during the congress, that ustekinumab can be restarted after a hiatus with very good results.

Dr. Griffiths disclosed that he serves on the advisory boards for and has received research grants from numerous pharmaceutical companies.

The vast majority of medical talks on biologic therapy for psoriasis focus on starting and maintaining the medications. Stopping biologics is a seldom-discussed topic, yet one that physicians often need to address.

"We’ve all got patients who are on biologic therapy who are completely clear of their psoriasis, and you’re constantly wondering, ‘Should I stop the biologic? Do they need to have that treatment anymore? Can I reduce the dosing frequency?’ The simplest answer is that in most cases, it’s probably not a good idea to stop unless there’s a good reason for doing so. It has been shown in most of the big clinical trials that if you stop therapy, the psoriasis will relapse at some point," Dr. Christopher Griffiths said at the annual congress of the European Academy of Dermatology and Venereology.

"With long-term therapy beyond 6-12 months, can biologics be stopped or produce remission? In most cases, no. And there’s no biomarker for disease activity as of yet to guide us," added Dr. Griffiths, professor of dermatology and associate dean for research at the University of Manchester (England).

Compelling reasons to stop biologic therapy include failure to achieve or maintain significant clinical improvement, serious adverse events, impending elective major surgery, certain vaccinations, and pregnancy. Dr. Griffiths highlighted the following points:

• Lack of Effectiveness. Today’s biologics are not curative. In a recent French report, only 31 of 86 psoriasis patients (36%) who started on etanercept (Enbrel), infliximab (Remicade), or efalizumab were still on the same biologic agent 24 months later (J. Dermatol. Treat. 2011;22:151-2). Similarly, the Danish national psoriasis database experience has been that roughly 40% of patients started on etanercept or adalimumab (Humira) were still on the medication 4 years later, as were 70% of those who started on infliximab (Br. J. Dermatol. 2011;164:1091-6).

The good news, Dr. Griffiths continued, is that lack of effectiveness for anti–tumor necrosis factor agents is not a class effect. He and his coinvestigators have reported that 21 of 31 psoriasis patients who switched to adalimumab from another anti-TNF biologic for lack of efficacy met the NICE (U.K. National Institute for Health and Clinical Excellence) criteria for adalimumab treatment continuation at 16 weeks (Br. J. Dermatol. 2010;163:859-62).

"Each anti-TNF drug is different, so if you fail one it doesn’t mean you’re going to fail another. That’s a very important point, and a very strong argument in your favor when dealing with payers. And it’s an observation that can only come from real-life data from a cohort study; you’re not going to get that information from clinical trials," the dermatologist explained.

The NICE criteria for continuation of biologic therapy bring an element of strict objectivity to treatment decision making in a rationed health care system. For British psoriasis patients to continue on a given biologic agent, they have to demonstrate a PASI 75 response (that is, a 75% improvement over the baseline Psoriasis Area and Severity Index score) at 16 weeks, or a PASI 50 response plus a 5-point drop in the Dermatology Life Quality Index (DLQI).

When physicians switch biologics, Dr. Griffiths recommends that they skip a lengthy washout period because of the associated risk of a severe, hard-to-control flare. His practice is to stop one and start another.

• Major Elective Surgery. There is a dearth of data on stopping biologics in psoriasis patients who plan to undergo elective surgery. The best practice for now, in Dr. Griffiths’ view, is to follow the British Society for Rheumatology guidance, which is based on an extensive biologics register the group maintains for rheumatoid arthritis.

The rheumatologists’ advice is to halt effective biologic therapy only for truly major surgery, and to stop anti-TNF drugs more than four half-lives before the operation. That’s 2-3 weeks beforehand for etanercept, 6-8 weeks for adalimumab, and 4-6 weeks for infliximab. There are no firm data for ustekinumab (Stelara) as yet, but experts advise halting it 12 weeks before surgery. Biologic therapy should be resumed as soon as possible postoperatively.

• Pregnancy. Again, a paucity of data exists on biologics for psoriasis in pregnancy. But the data accumulating in the British Society for Rheumatology Biologics Register (BSRBR) is reassuring. Although the rheumatologists recommend that pregnancy be avoided in patients on biologics, the experience to date in pregnant rheumatoid arthritis patients suggests there is little to no risk to the fetus. Breastfeeding should be avoided by women on biologic therapy other than infliximab, which is not excreted in breast milk, Dr. Griffiths continued.

• Vaccinations. British Association of Dermatologists guidelines on the use of biologics for psoriasis (Br. J. Dermatol. 2009;161:987-1019), which Dr. Griffiths coauthored and which will be updated in late 2012, recommend avoiding giving live or attenuated virus vaccines within 2 weeks prior to starting a patient on biologic therapy, or while the patient is on a biologic, or for up to 6 months after the patient stops the biologic. Inactivated virus vaccines are safe for patients on biologic therapy, although the antibody response will be somewhat less robust in a patient on an anti-TNF agent than in other individuals.

"But we advise – as should you – that all patients on biologics should receive influenza and pneumococcal vaccines. It’s just good clinical practice because these patients are by definition in a high-risk category," he said.

• Stopping and Restarting Biologics. It’s well established that etanercept can be used intermittently with good results. That is, a patient might use etanercept to good effect for 6 months, stop it, then restart when relapse occurs, and the agent will still remain effective. The same typically holds true for alefacept (Amevive).

In contrast, infliximab can realistically be used for only a single course of treatment. If a patient goes off the drug and later goes back on it, the chances of regaining a response are very low because of the formation of blocking antibodies.

The picture regarding the intermittent use of adalimumab is less clear. There are documented cases in which this agent hasn’t been effective any longer upon second usage.

There is good new evidence, presented by Dr. Griffiths elsewhere during the congress, that ustekinumab can be restarted after a hiatus with very good results.

Dr. Griffiths disclosed that he serves on the advisory boards for and has received research grants from numerous pharmaceutical companies.