As Dr. Van Voorhees observes in this month’s column, transitions in psoriasis treatment — as in life — often require adjustments. Here she offers her own strategies to best manage changing treatments. Transitions in my opinion are always a challenge. At each of life’s stages, the path to the new place is often a bit rocky, even when the opportunities ahead look enticing. It has always struck me that these times can be fraught with missteps as we learn the rules, test the waters and establish our bearings. Losing one’s comfort zone is not an easy task for most of us. It also strikes me that transitions can be a challenge in medicine, as is often the case in the treatment of chronic diseases. In an ideal world, patients are started on a medication that works perfectly without any complications and they are able to remain on that medication chronically. But, of course, that is not reality — at least not for most patients in my practice. For various reasons, patients may need to be switched from one medication to another. The need to make a change can come up when one is using both topical and systemic medications. Handling those transitions well is the art of working with psoriasis medications.
“Feathering” Topicals
Let’s start by talking about transitions when using topical therapies. We all have learned that the use of Class 1 steroids should be restricted to a few weeks because of concerns of cutaneous atrophy locally and possible systemic absorption. Since psoriasis lesions can persist longer than a few weeks, inevitably a switch among the topical medications is needed. When considering the switch to a vitamin D preparation or a combination vitamin D/class 2 steroid product or a lower potency topical steroid, I recommend against just stopping the class 1 steroid “cold turkey.” I find that a simple but effective strategy is to have patients “feather” out their use of the stronger product over time. I instruct them to use the stronger product intermittently in order to wean their dependence off the stronger product a little more slowly. Sometimes I’ll have them continue that intermittent usage on a continuous basis, hoping to retain some of the advantages of the stronger product while minimizing the potential side effects and risks of daily use. Unfortunately, there are no good, evidence-based studies confirming the safety of this approach, such as with the class 1 topical steroids, but patients seem to wind up using less of the more potent medications that way.
Transition Strategies for Systemic Medications
The situation where I find the art of transitioning medications really comes to the fore though is in prescribing systemic therapy for my psoriasis patients. Several scenarios often arise. When A Patient Fails To Respond To An Agent Most clear-cut is when a patient given an agent — say drug A — for an appropriate amount of time has absolutely no response. Since drug A has contributed nothing to controlling the patient’s skin, it can be stopped without any concern for a flare off treatment. In this situation I’ll simply stop the first medication and plan to start my second systemic medication. No transitioning steps are required in this scenario. When an Initially Effective Agent Loses Efficacy It is more common — and complicated, from a prescribing perspective — when a patient initially responds well to drug A, only to find that it loses some of its efficacy over time. Here, the specifics of the particular medications become the crucial fact. The transition is greatly facilitated by knowing how quickly the “new” medication might really “kick in” and how slowly the first medication will no longer have a therapeutic effect. So let’s take a few possible specific situations. Medication Overlap Strategies. If a patient is starting to do poorly on acitretin and I need to quickly improve their skin, I might choose to start cyclosporine. Since cyclosporine works very quickly, there is little need for overlap of these two medications. Transitioning is again a minimal concern. However, had I instead chosen etanercept, which can take up to 12 weeks to take effect, I would have overlapped the acitretin and etanercept for 8 weeks. The advantage of this overlap is twofold. First, it allows the patient’s skin to not flare in the time that the newly introduced medication is “getting going.” This strategy acknowledges the fact that the first medication is partially controlling the patient’s psoriasis; stopping the first medication abruptly will result in a loss of that partial disease control. Therefore, I want to be sure that the second medication has a chance to be more fully effective before the first medication is completely discontinued. Secondly, I think that there is often an additive advantage when two medications are used in combination, and this can allow for more complete control as the second medication is started. Methotrexate.I find, often takes about 8 weeks to become effective. When transitioning from acitretin to methotrexate, I therefore would overlap the two medications for about 4 weeks, giving the methotrexate a chance to get started before stopping the acitretin. Adalimumab starts working more quickly, so I might overlap acitretin and adalimumab for only 2 weeks. Infliximab also works quickly, so as with cyclosporine, little to no overlap is needed. I might overlap for ustekinumab for 12 weeks. Alefacept requires the longest overlap, since it is the slowest of the psoriasis medications to become effective; 14 weeks is what I would aim for. The key to deciding how long to overlap the medications should be based on how long it takes on average for the new medication to become effective and how long-lived the prior medication is in the body. Medication Risk Considerations. The same principles to transitioning medications apply in several other situations. Transitioning medications is important as well if the decision is made because of concern about possible long-term risks of a given medication. This might be a situation such as when one wants to transition from cyclosporine to an alternative medication to minimize the risk of renal toxicity. It is also important when transitioning a patient from two medications to one medication. In each of these situations slowly withdrawing the medication that is to be stopped is generally a good strategy. No one who has had their skin clear wants to see the gains lost by a flare from a medication being discontinued too quickly, especially if there is not an urgent need to have the former medication discontinued. For example, if a young man on both methotrexate and etanercept wants to stop methotrexate since abstinence from drinking alcohol is a social problem, I might suggest that we put him on a tapering schedule of decreasing his methotrexate dose by 2.5 mg/week each month. So if he was on 15 mg methotrexate weekly at the beginning, then it would take about 5 to 6 months to discontinue the methotrexate completely. This timeline needs to be discussed with the patient and adapted accordingly, but I find most patients are happy to work with this schedule when they understand its advantages.
Multiple Medication Risks
Often I’m asked about the cumulative risks of overlapping multiple medications. Unfortunately, this is an area where further investigation is sorely required. Little is known about potential risks. One has to be aware of potential risks of the individual medications and continue to monitor for them during this time. One also has to be sure that there are no known contraindications to the combination of the overlapping medications. For example, in transitioning a patient from cyclosporine to methotrexate, it is important to be aware of both possible hepatic and renal risks. Methotrexate can cause hepatotoxicity and is excreted by the kidneys, and cyclosporine can cause renal toxicity and is metabolized by the liver. Therefore, careful monitoring of both liver and renal studies is prudent. Some transitioning choices may be preferred over others. While cyclosporine has renal toxicity, the TNF inhibitors do not, so this overlap may have some potential advantages. The specifics of the patient’s medical history and their personal preferences also always need to be factored into the decision. The one sequence that I try to avoid is using cyclosporine if a patient has previously had extensive PUVA photochemotherapy. This can increase a patient’s risk for the development of NMSC — especially those of the squamous cell type. Whether our newer immunosuppressive therapies such as the TNF inhibitors and IL12/23 compounds will cause this same issue remains to be seen. So far, I have not seen this causing this concern in my patient population. As the number of patients who have previously been treated with long-term PUVA diminishes, I anticipate that this will become less of a concern. It is not clear whether the rotation of medications from one systemic therapy to another truly lessens the risk of toxicity developing. And while it intuitively makes sense, we need to continue to pay attention and monitor patients very closely.
It’s a Plan
I do believe that despite its possible perils, the overlapping of medications in some situations is the best strategy for patients. It is important though that you have a plan for how long that this overlap is to occur and stick with it unless a concern develops. Patients should understand your plan and find it acceptable. Patients need to be monitored for possible risks of both medications during this transition time. When executed well, patients really appreciate having their psoriasis managed successfully, and happy patients make it a better day for us all. Dr. Van Voorhees is Associate Professor, University of Pennsylvania Health System and Director of its Psoriasis and Phototherapy Treatment Center. Disclosure: The author has been a paid consultant/advisor or investigator for Amgen, Centocor and Leo.
As Dr. Van Voorhees observes in this month’s column, transitions in psoriasis treatment — as in life — often require adjustments. Here she offers her own strategies to best manage changing treatments. Transitions in my opinion are always a challenge. At each of life’s stages, the path to the new place is often a bit rocky, even when the opportunities ahead look enticing. It has always struck me that these times can be fraught with missteps as we learn the rules, test the waters and establish our bearings. Losing one’s comfort zone is not an easy task for most of us. It also strikes me that transitions can be a challenge in medicine, as is often the case in the treatment of chronic diseases. In an ideal world, patients are started on a medication that works perfectly without any complications and they are able to remain on that medication chronically. But, of course, that is not reality — at least not for most patients in my practice. For various reasons, patients may need to be switched from one medication to another. The need to make a change can come up when one is using both topical and systemic medications. Handling those transitions well is the art of working with psoriasis medications.
“Feathering” Topicals
Let’s start by talking about transitions when using topical therapies. We all have learned that the use of Class 1 steroids should be restricted to a few weeks because of concerns of cutaneous atrophy locally and possible systemic absorption. Since psoriasis lesions can persist longer than a few weeks, inevitably a switch among the topical medications is needed. When considering the switch to a vitamin D preparation or a combination vitamin D/class 2 steroid product or a lower potency topical steroid, I recommend against just stopping the class 1 steroid “cold turkey.” I find that a simple but effective strategy is to have patients “feather” out their use of the stronger product over time. I instruct them to use the stronger product intermittently in order to wean their dependence off the stronger product a little more slowly. Sometimes I’ll have them continue that intermittent usage on a continuous basis, hoping to retain some of the advantages of the stronger product while minimizing the potential side effects and risks of daily use. Unfortunately, there are no good, evidence-based studies confirming the safety of this approach, such as with the class 1 topical steroids, but patients seem to wind up using less of the more potent medications that way.
Transition Strategies for Systemic Medications
The situation where I find the art of transitioning medications really comes to the fore though is in prescribing systemic therapy for my psoriasis patients. Several scenarios often arise. When A Patient Fails To Respond To An Agent Most clear-cut is when a patient given an agent — say drug A — for an appropriate amount of time has absolutely no response. Since drug A has contributed nothing to controlling the patient’s skin, it can be stopped without any concern for a flare off treatment. In this situation I’ll simply stop the first medication and plan to start my second systemic medication. No transitioning steps are required in this scenario. When an Initially Effective Agent Loses Efficacy It is more common — and complicated, from a prescribing perspective — when a patient initially responds well to drug A, only to find that it loses some of its efficacy over time. Here, the specifics of the particular medications become the crucial fact. The transition is greatly facilitated by knowing how quickly the “new” medication might really “kick in” and how slowly the first medication will no longer have a therapeutic effect. So let’s take a few possible specific situations. Medication Overlap Strategies. If a patient is starting to do poorly on acitretin and I need to quickly improve their skin, I might choose to start cyclosporine. Since cyclosporine works very quickly, there is little need for overlap of these two medications. Transitioning is again a minimal concern. However, had I instead chosen etanercept, which can take up to 12 weeks to take effect, I would have overlapped the acitretin and etanercept for 8 weeks. The advantage of this overlap is twofold. First, it allows the patient’s skin to not flare in the time that the newly introduced medication is “getting going.” This strategy acknowledges the fact that the first medication is partially controlling the patient’s psoriasis; stopping the first medication abruptly will result in a loss of that partial disease control. Therefore, I want to be sure that the second medication has a chance to be more fully effective before the first medication is completely discontinued. Secondly, I think that there is often an additive advantage when two medications are used in combination, and this can allow for more complete control as the second medication is started. Methotrexate.I find, often takes about 8 weeks to become effective. When transitioning from acitretin to methotrexate, I therefore would overlap the two medications for about 4 weeks, giving the methotrexate a chance to get started before stopping the acitretin. Adalimumab starts working more quickly, so I might overlap acitretin and adalimumab for only 2 weeks. Infliximab also works quickly, so as with cyclosporine, little to no overlap is needed. I might overlap for ustekinumab for 12 weeks. Alefacept requires the longest overlap, since it is the slowest of the psoriasis medications to become effective; 14 weeks is what I would aim for. The key to deciding how long to overlap the medications should be based on how long it takes on average for the new medication to become effective and how long-lived the prior medication is in the body. Medication Risk Considerations. The same principles to transitioning medications apply in several other situations. Transitioning medications is important as well if the decision is made because of concern about possible long-term risks of a given medication. This might be a situation such as when one wants to transition from cyclosporine to an alternative medication to minimize the risk of renal toxicity. It is also important when transitioning a patient from two medications to one medication. In each of these situations slowly withdrawing the medication that is to be stopped is generally a good strategy. No one who has had their skin clear wants to see the gains lost by a flare from a medication being discontinued too quickly, especially if there is not an urgent need to have the former medication discontinued. For example, if a young man on both methotrexate and etanercept wants to stop methotrexate since abstinence from drinking alcohol is a social problem, I might suggest that we put him on a tapering schedule of decreasing his methotrexate dose by 2.5 mg/week each month. So if he was on 15 mg methotrexate weekly at the beginning, then it would take about 5 to 6 months to discontinue the methotrexate completely. This timeline needs to be discussed with the patient and adapted accordingly, but I find most patients are happy to work with this schedule when they understand its advantages.
Multiple Medication Risks
Often I’m asked about the cumulative risks of overlapping multiple medications. Unfortunately, this is an area where further investigation is sorely required. Little is known about potential risks. One has to be aware of potential risks of the individual medications and continue to monitor for them during this time. One also has to be sure that there are no known contraindications to the combination of the overlapping medications. For example, in transitioning a patient from cyclosporine to methotrexate, it is important to be aware of both possible hepatic and renal risks. Methotrexate can cause hepatotoxicity and is excreted by the kidneys, and cyclosporine can cause renal toxicity and is metabolized by the liver. Therefore, careful monitoring of both liver and renal studies is prudent. Some transitioning choices may be preferred over others. While cyclosporine has renal toxicity, the TNF inhibitors do not, so this overlap may have some potential advantages. The specifics of the patient’s medical history and their personal preferences also always need to be factored into the decision. The one sequence that I try to avoid is using cyclosporine if a patient has previously had extensive PUVA photochemotherapy. This can increase a patient’s risk for the development of NMSC — especially those of the squamous cell type. Whether our newer immunosuppressive therapies such as the TNF inhibitors and IL12/23 compounds will cause this same issue remains to be seen. So far, I have not seen this causing this concern in my patient population. As the number of patients who have previously been treated with long-term PUVA diminishes, I anticipate that this will become less of a concern. It is not clear whether the rotation of medications from one systemic therapy to another truly lessens the risk of toxicity developing. And while it intuitively makes sense, we need to continue to pay attention and monitor patients very closely.
It’s a Plan
I do believe that despite its possible perils, the overlapping of medications in some situations is the best strategy for patients. It is important though that you have a plan for how long that this overlap is to occur and stick with it unless a concern develops. Patients should understand your plan and find it acceptable. Patients need to be monitored for possible risks of both medications during this transition time. When executed well, patients really appreciate having their psoriasis managed successfully, and happy patients make it a better day for us all. Dr. Van Voorhees is Associate Professor, University of Pennsylvania Health System and Director of its Psoriasis and Phototherapy Treatment Center. Disclosure: The author has been a paid consultant/advisor or investigator for Amgen, Centocor and Leo.
As Dr. Van Voorhees observes in this month’s column, transitions in psoriasis treatment — as in life — often require adjustments. Here she offers her own strategies to best manage changing treatments. Transitions in my opinion are always a challenge. At each of life’s stages, the path to the new place is often a bit rocky, even when the opportunities ahead look enticing. It has always struck me that these times can be fraught with missteps as we learn the rules, test the waters and establish our bearings. Losing one’s comfort zone is not an easy task for most of us. It also strikes me that transitions can be a challenge in medicine, as is often the case in the treatment of chronic diseases. In an ideal world, patients are started on a medication that works perfectly without any complications and they are able to remain on that medication chronically. But, of course, that is not reality — at least not for most patients in my practice. For various reasons, patients may need to be switched from one medication to another. The need to make a change can come up when one is using both topical and systemic medications. Handling those transitions well is the art of working with psoriasis medications.
“Feathering” Topicals
Let’s start by talking about transitions when using topical therapies. We all have learned that the use of Class 1 steroids should be restricted to a few weeks because of concerns of cutaneous atrophy locally and possible systemic absorption. Since psoriasis lesions can persist longer than a few weeks, inevitably a switch among the topical medications is needed. When considering the switch to a vitamin D preparation or a combination vitamin D/class 2 steroid product or a lower potency topical steroid, I recommend against just stopping the class 1 steroid “cold turkey.” I find that a simple but effective strategy is to have patients “feather” out their use of the stronger product over time. I instruct them to use the stronger product intermittently in order to wean their dependence off the stronger product a little more slowly. Sometimes I’ll have them continue that intermittent usage on a continuous basis, hoping to retain some of the advantages of the stronger product while minimizing the potential side effects and risks of daily use. Unfortunately, there are no good, evidence-based studies confirming the safety of this approach, such as with the class 1 topical steroids, but patients seem to wind up using less of the more potent medications that way.
Transition Strategies for Systemic Medications
The situation where I find the art of transitioning medications really comes to the fore though is in prescribing systemic therapy for my psoriasis patients. Several scenarios often arise. When A Patient Fails To Respond To An Agent Most clear-cut is when a patient given an agent — say drug A — for an appropriate amount of time has absolutely no response. Since drug A has contributed nothing to controlling the patient’s skin, it can be stopped without any concern for a flare off treatment. In this situation I’ll simply stop the first medication and plan to start my second systemic medication. No transitioning steps are required in this scenario. When an Initially Effective Agent Loses Efficacy It is more common — and complicated, from a prescribing perspective — when a patient initially responds well to drug A, only to find that it loses some of its efficacy over time. Here, the specifics of the particular medications become the crucial fact. The transition is greatly facilitated by knowing how quickly the “new” medication might really “kick in” and how slowly the first medication will no longer have a therapeutic effect. So let’s take a few possible specific situations. Medication Overlap Strategies. If a patient is starting to do poorly on acitretin and I need to quickly improve their skin, I might choose to start cyclosporine. Since cyclosporine works very quickly, there is little need for overlap of these two medications. Transitioning is again a minimal concern. However, had I instead chosen etanercept, which can take up to 12 weeks to take effect, I would have overlapped the acitretin and etanercept for 8 weeks. The advantage of this overlap is twofold. First, it allows the patient’s skin to not flare in the time that the newly introduced medication is “getting going.” This strategy acknowledges the fact that the first medication is partially controlling the patient’s psoriasis; stopping the first medication abruptly will result in a loss of that partial disease control. Therefore, I want to be sure that the second medication has a chance to be more fully effective before the first medication is completely discontinued. Secondly, I think that there is often an additive advantage when two medications are used in combination, and this can allow for more complete control as the second medication is started. Methotrexate.I find, often takes about 8 weeks to become effective. When transitioning from acitretin to methotrexate, I therefore would overlap the two medications for about 4 weeks, giving the methotrexate a chance to get started before stopping the acitretin. Adalimumab starts working more quickly, so I might overlap acitretin and adalimumab for only 2 weeks. Infliximab also works quickly, so as with cyclosporine, little to no overlap is needed. I might overlap for ustekinumab for 12 weeks. Alefacept requires the longest overlap, since it is the slowest of the psoriasis medications to become effective; 14 weeks is what I would aim for. The key to deciding how long to overlap the medications should be based on how long it takes on average for the new medication to become effective and how long-lived the prior medication is in the body. Medication Risk Considerations. The same principles to transitioning medications apply in several other situations. Transitioning medications is important as well if the decision is made because of concern about possible long-term risks of a given medication. This might be a situation such as when one wants to transition from cyclosporine to an alternative medication to minimize the risk of renal toxicity. It is also important when transitioning a patient from two medications to one medication. In each of these situations slowly withdrawing the medication that is to be stopped is generally a good strategy. No one who has had their skin clear wants to see the gains lost by a flare from a medication being discontinued too quickly, especially if there is not an urgent need to have the former medication discontinued. For example, if a young man on both methotrexate and etanercept wants to stop methotrexate since abstinence from drinking alcohol is a social problem, I might suggest that we put him on a tapering schedule of decreasing his methotrexate dose by 2.5 mg/week each month. So if he was on 15 mg methotrexate weekly at the beginning, then it would take about 5 to 6 months to discontinue the methotrexate completely. This timeline needs to be discussed with the patient and adapted accordingly, but I find most patients are happy to work with this schedule when they understand its advantages.
Multiple Medication Risks
Often I’m asked about the cumulative risks of overlapping multiple medications. Unfortunately, this is an area where further investigation is sorely required. Little is known about potential risks. One has to be aware of potential risks of the individual medications and continue to monitor for them during this time. One also has to be sure that there are no known contraindications to the combination of the overlapping medications. For example, in transitioning a patient from cyclosporine to methotrexate, it is important to be aware of both possible hepatic and renal risks. Methotrexate can cause hepatotoxicity and is excreted by the kidneys, and cyclosporine can cause renal toxicity and is metabolized by the liver. Therefore, careful monitoring of both liver and renal studies is prudent. Some transitioning choices may be preferred over others. While cyclosporine has renal toxicity, the TNF inhibitors do not, so this overlap may have some potential advantages. The specifics of the patient’s medical history and their personal preferences also always need to be factored into the decision. The one sequence that I try to avoid is using cyclosporine if a patient has previously had extensive PUVA photochemotherapy. This can increase a patient’s risk for the development of NMSC — especially those of the squamous cell type. Whether our newer immunosuppressive therapies such as the TNF inhibitors and IL12/23 compounds will cause this same issue remains to be seen. So far, I have not seen this causing this concern in my patient population. As the number of patients who have previously been treated with long-term PUVA diminishes, I anticipate that this will become less of a concern. It is not clear whether the rotation of medications from one systemic therapy to another truly lessens the risk of toxicity developing. And while it intuitively makes sense, we need to continue to pay attention and monitor patients very closely.
It’s a Plan
I do believe that despite its possible perils, the overlapping of medications in some situations is the best strategy for patients. It is important though that you have a plan for how long that this overlap is to occur and stick with it unless a concern develops. Patients should understand your plan and find it acceptable. Patients need to be monitored for possible risks of both medications during this transition time. When executed well, patients really appreciate having their psoriasis managed successfully, and happy patients make it a better day for us all. Dr. Van Voorhees is Associate Professor, University of Pennsylvania Health System and Director of its Psoriasis and Phototherapy Treatment Center. Disclosure: The author has been a paid consultant/advisor or investigator for Amgen, Centocor and Leo.
