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Once a rheumatoid arthritis patient maintains relatively long-term remission on a regimen that combines a synthetic and a biologic disease-modifying drug, temptation mounts to try withdrawing one of the two drugs. Cost considerations alone can make it irresistible to patients to taper down or stop an expensive biologic drug to see whether the patient’s remission can sustain dose reduction or elimination.
But several American experts cautioned that despite growing evidence that at least some rheumatoid arthritis (RA) patients will stay in remission after their biologic disease-modifying antirheumatic drug (DMARD) is gone, the overall efficacy and safety of this approach remain uncertain and it’s not fully clear which patients are the best candidates. Biologic-drug withdrawal has not repeatedly been shown to be fully safe and worth attempting with results from rigorously controlled and adequately powered studies, an evidence base that may still be several years off.
"We can try withdrawing a drug," and many American RA patients do just that, a step more often than not initiated by the patient. "But we don’t know if it’s benign for radiographic progression or for cardiovascular disease events," said Dr. Arthur Weinstein, director of rheumatology at Washington (D.C.) Hospital Center. Even though RA patients in remission who taper down or fully stop their biologic DMARD are usually closely monitored for flare, "there is some evidence for a disconnect between radiographic progression and clinical status," raising the danger that a patient may appear to remain in remission when off the biologic drug while joint deterioration occurs. That, coupled with concern that an RA patient’s cardiovascular risk may worsen off their biologic, can make patients and physicians hesitate when faced with the prospect of messing with a stable remission on a combined biologic and synthetic DMARD regimen, Dr. Weinstein said in an interview.
Biologic withdrawal can succeed
Despite that, it’s undeniable that a substantial minority or even a majority in some series of RA patients in remission or low disease activity on both a biologic and synthetic DMARD can taper down or stop the biologic without a flare occurring. The flip side of that is, of course, that in many series a good number of patients who stop their biologic have a flare and need to have the drug restarted. The good news for these scenarios is that prompt restart of the biologic once a flare occurs generally seems capable of restoring remission with no long-term deleterious effects.
In its 2013 RA treatment guidelines, the European League Against Rheumatism (EULAR) said that "if a patient is in persistent remission after having tapered glucocorticoids, one can consider tapering biologic DMARDs, especially if this treatment is combined with a synthetic DMARD" (Ann. Rheum. Dis. 2014;73:492-509). The most recent RA management guidelines from the American College of Rheumatology, published in 2012, don’t address tapering down or withdrawing biologics. Dr. Weinstein noted that the EULAR recommendation is largely based on consensus expert opinion without a definitive evidence base to justify this approach.
Recent evidence documenting the success of biologic withdrawal includes a report earlier this year from a prespecified analysis in the OPTIMA (Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab) trial that detailed the outcomes of 207 patients who had stable, low disease activity on combined treatment with adalimumab (Humira) and methotrexate and were randomized to either adalimumab withdrawal or continuation. A year later, 70% of patients who maintained the two-drug regimen and 54% of those randomized to stop adalimumab remained at low disease activity and had no sign of radiographic progression, a between-group difference that was not statistically significant (Lancet 2014;383:321-32).
But in other studies, patients withdrawn from a biologic did not fare nearly as well. The PRESERVE (Maintenance, induction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis) trial randomized 604 RA patients with low disease activity on a combination of etanercept (Enbrel) and methotrexate to continue to receive 50 mg of etanercept plus methotrexate weekly, step down to 25 mg of etanercept plus methotrexate weekly, or completely stop etanercept and continue on methotrexate alone. A year later, the percentage of patients who remained in low disease activity tallied 83% in those who received at least one dose of 50 mg etanercept, 79% of patients in the 25-mg etanercept group, and 43% in the group maintained on methotrexate monotherapy, statistically significant differences between each of the two etanercept groups and the monotherapy arm (Lancet 2013;381:918-29).
A more real-world assessment included 717 RA patients at low disease activity who discontinued their first biologic drug while enrolled in the CORRONA (Consortium of Rheumatology Researchers of North America) registry. The results showed that after 1 year on monotherapy without a biologic, 73% of patients remained free from a flare, and that state persisted in 56% to 18 months, 42% after 2 years, and 28% after 3 years on monotherapy, Dr. Arthur F. Kavanaugh and his associates reported last year at the annual meeting of the American College of Rheumatology (Arthritis Rheum. 2013;65:S603).
Finding the right patients
Despite evidence like this, the right time and the right patient for withdrawing a biologic remain murky. "At this point it is investigational," said Dr. Kavanaugh in an interview. "In the United States, it is mostly initiated by patients. There are many factors to consider, including the duration of RA, how well the patients are doing, is the patient on another drug that should be stopped first such as prednisone, and can the synthetic DMARD like methotrexate sustain the response," said Dr. Kavanaugh, a rheumatologist who is professor of clinical medicine and director of the Center for Innovative Therapy at the University of California, San Diego.
Routinely attempting biologic taper-down or withdrawal from RA patients in remission or at low disease activity "is not yet standard practice, but many patients do it," said Dr. Joel M. Kremer, a rheumatologist and professor of medicine at Albany (N.Y.) Medical College. When he attempts withdrawing a biologic, he prefers to use a gradual taper-down of the dosage, and he said he is more reluctant to attempt this for patients who began treatment with severe RA, and that he is more likely to try it for patients who began treatment with early RA, although he admitted that this remains uncertain. Like all experts interviewed, he said the type of biologic a patient is on doesn’t seem to matter.
"I think this entire area needs more study," Dr. Kremer said in an interview. For example, "are there biomarkers associated with the ability to withdraw? I don’t believe we know much about who can or should withdraw." Once withdrawal occurs, he recommended careful follow-up to detect a flare quickly, and restarting the biologic if even a mild flare occurs.
Biologic withdrawal "is really more investigational" right now, said Dr. Eric L. Matteson, professor and chairman of rheumatology at the Mayo Clinic in Rochester, Minn. "No guideline establishes it as standard of practice. I like to see patients in full remission for a year before considering such a move," he said in an interview. Withdrawal depends on whether the RA is well controlled and not on whether treatment started on early or established RA, he added; nor did he think that a flare after withdrawal precludes future withdrawal attempts as long as the patient returns to a durable, full remission. But Dr. Matteson did caution about also considering extra-articular disease like vasculitis or iritis that may be active even when a patient’s joints are not. "Any evidence of recurrent disease should cause the patient and physician to consider ramping the therapy back up."
Like others, Dr. Matteson highlighted the lingering unknowns about biologic withdrawal that keep it from being standard practice. "We don’t know whether the biologic or synthetic DMARD should get withdrawn first. We don’t have a great handle on what biomarkers to use to help decide if there is subclinical disease activity that necessitates reimplementation of the biologic. We don’t know which patients may violently flare following withdrawal and which might not. We also don’t know if retreatment of the disease is as good when a biologic is withdrawn and then restarted. Finally, I think we overestimate the percent of our patients who are actually in remission or a low-disease-activity state and underestimate who really should continue their medications."
The STARA trial
Dr. Weinstein and his associates recently planned a U.S.-based trial that has come close to launching to address several of these issues, the STARA (Stopping TNF-Alpha Inhibitors in Rheumatoid Arthritis) trial.
"One aspect of STARA is to determine whether there is a profile of clinical, imaging, and laboratory factors that will reliably distinguish patients who will flare from those who will remain in remission" following withdrawal of a biologic DMARD, said Dr. Weinstein, STARA’s lead investigator and also a professor of medicine at Georgetown University in Washington. "Another aim is to find predictors of good candidates for withdrawal. The advantage of STARA is patients are drawn from real-world practice and not from a clinical trial." Dr. Weinstein faulted some of the published studies of biologic withdrawal, such as OPTIMA and PRESERVE, because they included trial patients exclusively and not patients managed in routine practice.
STARA’s design uses a sudden, full withdrawal of the biologic to allow a standardized approach to patients who could enter the study on etanercept, adalimumab, or infliximab (Remicade). For routine practice, gradual withdrawal is more common, though there is no evidence this produces better long-term outcomes. An important withdrawal question that STARA won’t address is: Which is the better drug to remove, the biologic or the synthetic DMARD? In most cases, the more expensive biologic is the patient’s choice, but ideally this issue should be addressed in a randomized trial, Dr. Weinstein said.
But as of late March, STARA’s status was in doubt, as anticipated funding was withdrawn. If STARA isn’t run, Dr. Weinstein predicts that attempts to cut biologics from dual regimens will continue and likely expand, but with unknown implications for long-term safety that he believes can only be addressed in a prospective, randomized trial.
Dr. Weinstein said that he had no relevant disclosures. Dr. Matteson had no disclosures. Dr. Kremer has received research support and been a consultant to more than 10 drug companies. Dr. Kavanaugh has received research support from more than 10 drug companies.
On Twitter @mitchelzoler
Once a rheumatoid arthritis patient maintains relatively long-term remission on a regimen that combines a synthetic and a biologic disease-modifying drug, temptation mounts to try withdrawing one of the two drugs. Cost considerations alone can make it irresistible to patients to taper down or stop an expensive biologic drug to see whether the patient’s remission can sustain dose reduction or elimination.
But several American experts cautioned that despite growing evidence that at least some rheumatoid arthritis (RA) patients will stay in remission after their biologic disease-modifying antirheumatic drug (DMARD) is gone, the overall efficacy and safety of this approach remain uncertain and it’s not fully clear which patients are the best candidates. Biologic-drug withdrawal has not repeatedly been shown to be fully safe and worth attempting with results from rigorously controlled and adequately powered studies, an evidence base that may still be several years off.
"We can try withdrawing a drug," and many American RA patients do just that, a step more often than not initiated by the patient. "But we don’t know if it’s benign for radiographic progression or for cardiovascular disease events," said Dr. Arthur Weinstein, director of rheumatology at Washington (D.C.) Hospital Center. Even though RA patients in remission who taper down or fully stop their biologic DMARD are usually closely monitored for flare, "there is some evidence for a disconnect between radiographic progression and clinical status," raising the danger that a patient may appear to remain in remission when off the biologic drug while joint deterioration occurs. That, coupled with concern that an RA patient’s cardiovascular risk may worsen off their biologic, can make patients and physicians hesitate when faced with the prospect of messing with a stable remission on a combined biologic and synthetic DMARD regimen, Dr. Weinstein said in an interview.
Biologic withdrawal can succeed
Despite that, it’s undeniable that a substantial minority or even a majority in some series of RA patients in remission or low disease activity on both a biologic and synthetic DMARD can taper down or stop the biologic without a flare occurring. The flip side of that is, of course, that in many series a good number of patients who stop their biologic have a flare and need to have the drug restarted. The good news for these scenarios is that prompt restart of the biologic once a flare occurs generally seems capable of restoring remission with no long-term deleterious effects.
In its 2013 RA treatment guidelines, the European League Against Rheumatism (EULAR) said that "if a patient is in persistent remission after having tapered glucocorticoids, one can consider tapering biologic DMARDs, especially if this treatment is combined with a synthetic DMARD" (Ann. Rheum. Dis. 2014;73:492-509). The most recent RA management guidelines from the American College of Rheumatology, published in 2012, don’t address tapering down or withdrawing biologics. Dr. Weinstein noted that the EULAR recommendation is largely based on consensus expert opinion without a definitive evidence base to justify this approach.
Recent evidence documenting the success of biologic withdrawal includes a report earlier this year from a prespecified analysis in the OPTIMA (Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab) trial that detailed the outcomes of 207 patients who had stable, low disease activity on combined treatment with adalimumab (Humira) and methotrexate and were randomized to either adalimumab withdrawal or continuation. A year later, 70% of patients who maintained the two-drug regimen and 54% of those randomized to stop adalimumab remained at low disease activity and had no sign of radiographic progression, a between-group difference that was not statistically significant (Lancet 2014;383:321-32).
But in other studies, patients withdrawn from a biologic did not fare nearly as well. The PRESERVE (Maintenance, induction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis) trial randomized 604 RA patients with low disease activity on a combination of etanercept (Enbrel) and methotrexate to continue to receive 50 mg of etanercept plus methotrexate weekly, step down to 25 mg of etanercept plus methotrexate weekly, or completely stop etanercept and continue on methotrexate alone. A year later, the percentage of patients who remained in low disease activity tallied 83% in those who received at least one dose of 50 mg etanercept, 79% of patients in the 25-mg etanercept group, and 43% in the group maintained on methotrexate monotherapy, statistically significant differences between each of the two etanercept groups and the monotherapy arm (Lancet 2013;381:918-29).
A more real-world assessment included 717 RA patients at low disease activity who discontinued their first biologic drug while enrolled in the CORRONA (Consortium of Rheumatology Researchers of North America) registry. The results showed that after 1 year on monotherapy without a biologic, 73% of patients remained free from a flare, and that state persisted in 56% to 18 months, 42% after 2 years, and 28% after 3 years on monotherapy, Dr. Arthur F. Kavanaugh and his associates reported last year at the annual meeting of the American College of Rheumatology (Arthritis Rheum. 2013;65:S603).
Finding the right patients
Despite evidence like this, the right time and the right patient for withdrawing a biologic remain murky. "At this point it is investigational," said Dr. Kavanaugh in an interview. "In the United States, it is mostly initiated by patients. There are many factors to consider, including the duration of RA, how well the patients are doing, is the patient on another drug that should be stopped first such as prednisone, and can the synthetic DMARD like methotrexate sustain the response," said Dr. Kavanaugh, a rheumatologist who is professor of clinical medicine and director of the Center for Innovative Therapy at the University of California, San Diego.
Routinely attempting biologic taper-down or withdrawal from RA patients in remission or at low disease activity "is not yet standard practice, but many patients do it," said Dr. Joel M. Kremer, a rheumatologist and professor of medicine at Albany (N.Y.) Medical College. When he attempts withdrawing a biologic, he prefers to use a gradual taper-down of the dosage, and he said he is more reluctant to attempt this for patients who began treatment with severe RA, and that he is more likely to try it for patients who began treatment with early RA, although he admitted that this remains uncertain. Like all experts interviewed, he said the type of biologic a patient is on doesn’t seem to matter.
"I think this entire area needs more study," Dr. Kremer said in an interview. For example, "are there biomarkers associated with the ability to withdraw? I don’t believe we know much about who can or should withdraw." Once withdrawal occurs, he recommended careful follow-up to detect a flare quickly, and restarting the biologic if even a mild flare occurs.
Biologic withdrawal "is really more investigational" right now, said Dr. Eric L. Matteson, professor and chairman of rheumatology at the Mayo Clinic in Rochester, Minn. "No guideline establishes it as standard of practice. I like to see patients in full remission for a year before considering such a move," he said in an interview. Withdrawal depends on whether the RA is well controlled and not on whether treatment started on early or established RA, he added; nor did he think that a flare after withdrawal precludes future withdrawal attempts as long as the patient returns to a durable, full remission. But Dr. Matteson did caution about also considering extra-articular disease like vasculitis or iritis that may be active even when a patient’s joints are not. "Any evidence of recurrent disease should cause the patient and physician to consider ramping the therapy back up."
Like others, Dr. Matteson highlighted the lingering unknowns about biologic withdrawal that keep it from being standard practice. "We don’t know whether the biologic or synthetic DMARD should get withdrawn first. We don’t have a great handle on what biomarkers to use to help decide if there is subclinical disease activity that necessitates reimplementation of the biologic. We don’t know which patients may violently flare following withdrawal and which might not. We also don’t know if retreatment of the disease is as good when a biologic is withdrawn and then restarted. Finally, I think we overestimate the percent of our patients who are actually in remission or a low-disease-activity state and underestimate who really should continue their medications."
The STARA trial
Dr. Weinstein and his associates recently planned a U.S.-based trial that has come close to launching to address several of these issues, the STARA (Stopping TNF-Alpha Inhibitors in Rheumatoid Arthritis) trial.
"One aspect of STARA is to determine whether there is a profile of clinical, imaging, and laboratory factors that will reliably distinguish patients who will flare from those who will remain in remission" following withdrawal of a biologic DMARD, said Dr. Weinstein, STARA’s lead investigator and also a professor of medicine at Georgetown University in Washington. "Another aim is to find predictors of good candidates for withdrawal. The advantage of STARA is patients are drawn from real-world practice and not from a clinical trial." Dr. Weinstein faulted some of the published studies of biologic withdrawal, such as OPTIMA and PRESERVE, because they included trial patients exclusively and not patients managed in routine practice.
STARA’s design uses a sudden, full withdrawal of the biologic to allow a standardized approach to patients who could enter the study on etanercept, adalimumab, or infliximab (Remicade). For routine practice, gradual withdrawal is more common, though there is no evidence this produces better long-term outcomes. An important withdrawal question that STARA won’t address is: Which is the better drug to remove, the biologic or the synthetic DMARD? In most cases, the more expensive biologic is the patient’s choice, but ideally this issue should be addressed in a randomized trial, Dr. Weinstein said.
But as of late March, STARA’s status was in doubt, as anticipated funding was withdrawn. If STARA isn’t run, Dr. Weinstein predicts that attempts to cut biologics from dual regimens will continue and likely expand, but with unknown implications for long-term safety that he believes can only be addressed in a prospective, randomized trial.
Dr. Weinstein said that he had no relevant disclosures. Dr. Matteson had no disclosures. Dr. Kremer has received research support and been a consultant to more than 10 drug companies. Dr. Kavanaugh has received research support from more than 10 drug companies.
On Twitter @mitchelzoler
Once a rheumatoid arthritis patient maintains relatively long-term remission on a regimen that combines a synthetic and a biologic disease-modifying drug, temptation mounts to try withdrawing one of the two drugs. Cost considerations alone can make it irresistible to patients to taper down or stop an expensive biologic drug to see whether the patient’s remission can sustain dose reduction or elimination.
But several American experts cautioned that despite growing evidence that at least some rheumatoid arthritis (RA) patients will stay in remission after their biologic disease-modifying antirheumatic drug (DMARD) is gone, the overall efficacy and safety of this approach remain uncertain and it’s not fully clear which patients are the best candidates. Biologic-drug withdrawal has not repeatedly been shown to be fully safe and worth attempting with results from rigorously controlled and adequately powered studies, an evidence base that may still be several years off.
"We can try withdrawing a drug," and many American RA patients do just that, a step more often than not initiated by the patient. "But we don’t know if it’s benign for radiographic progression or for cardiovascular disease events," said Dr. Arthur Weinstein, director of rheumatology at Washington (D.C.) Hospital Center. Even though RA patients in remission who taper down or fully stop their biologic DMARD are usually closely monitored for flare, "there is some evidence for a disconnect between radiographic progression and clinical status," raising the danger that a patient may appear to remain in remission when off the biologic drug while joint deterioration occurs. That, coupled with concern that an RA patient’s cardiovascular risk may worsen off their biologic, can make patients and physicians hesitate when faced with the prospect of messing with a stable remission on a combined biologic and synthetic DMARD regimen, Dr. Weinstein said in an interview.
Biologic withdrawal can succeed
Despite that, it’s undeniable that a substantial minority or even a majority in some series of RA patients in remission or low disease activity on both a biologic and synthetic DMARD can taper down or stop the biologic without a flare occurring. The flip side of that is, of course, that in many series a good number of patients who stop their biologic have a flare and need to have the drug restarted. The good news for these scenarios is that prompt restart of the biologic once a flare occurs generally seems capable of restoring remission with no long-term deleterious effects.
In its 2013 RA treatment guidelines, the European League Against Rheumatism (EULAR) said that "if a patient is in persistent remission after having tapered glucocorticoids, one can consider tapering biologic DMARDs, especially if this treatment is combined with a synthetic DMARD" (Ann. Rheum. Dis. 2014;73:492-509). The most recent RA management guidelines from the American College of Rheumatology, published in 2012, don’t address tapering down or withdrawing biologics. Dr. Weinstein noted that the EULAR recommendation is largely based on consensus expert opinion without a definitive evidence base to justify this approach.
Recent evidence documenting the success of biologic withdrawal includes a report earlier this year from a prespecified analysis in the OPTIMA (Optimal Protocol for Treatment Initiation with Methotrexate and Adalimumab) trial that detailed the outcomes of 207 patients who had stable, low disease activity on combined treatment with adalimumab (Humira) and methotrexate and were randomized to either adalimumab withdrawal or continuation. A year later, 70% of patients who maintained the two-drug regimen and 54% of those randomized to stop adalimumab remained at low disease activity and had no sign of radiographic progression, a between-group difference that was not statistically significant (Lancet 2014;383:321-32).
But in other studies, patients withdrawn from a biologic did not fare nearly as well. The PRESERVE (Maintenance, induction, or withdrawal of etanercept after treatment with etanercept and methotrexate in patients with moderate rheumatoid arthritis) trial randomized 604 RA patients with low disease activity on a combination of etanercept (Enbrel) and methotrexate to continue to receive 50 mg of etanercept plus methotrexate weekly, step down to 25 mg of etanercept plus methotrexate weekly, or completely stop etanercept and continue on methotrexate alone. A year later, the percentage of patients who remained in low disease activity tallied 83% in those who received at least one dose of 50 mg etanercept, 79% of patients in the 25-mg etanercept group, and 43% in the group maintained on methotrexate monotherapy, statistically significant differences between each of the two etanercept groups and the monotherapy arm (Lancet 2013;381:918-29).
A more real-world assessment included 717 RA patients at low disease activity who discontinued their first biologic drug while enrolled in the CORRONA (Consortium of Rheumatology Researchers of North America) registry. The results showed that after 1 year on monotherapy without a biologic, 73% of patients remained free from a flare, and that state persisted in 56% to 18 months, 42% after 2 years, and 28% after 3 years on monotherapy, Dr. Arthur F. Kavanaugh and his associates reported last year at the annual meeting of the American College of Rheumatology (Arthritis Rheum. 2013;65:S603).
Finding the right patients
Despite evidence like this, the right time and the right patient for withdrawing a biologic remain murky. "At this point it is investigational," said Dr. Kavanaugh in an interview. "In the United States, it is mostly initiated by patients. There are many factors to consider, including the duration of RA, how well the patients are doing, is the patient on another drug that should be stopped first such as prednisone, and can the synthetic DMARD like methotrexate sustain the response," said Dr. Kavanaugh, a rheumatologist who is professor of clinical medicine and director of the Center for Innovative Therapy at the University of California, San Diego.
Routinely attempting biologic taper-down or withdrawal from RA patients in remission or at low disease activity "is not yet standard practice, but many patients do it," said Dr. Joel M. Kremer, a rheumatologist and professor of medicine at Albany (N.Y.) Medical College. When he attempts withdrawing a biologic, he prefers to use a gradual taper-down of the dosage, and he said he is more reluctant to attempt this for patients who began treatment with severe RA, and that he is more likely to try it for patients who began treatment with early RA, although he admitted that this remains uncertain. Like all experts interviewed, he said the type of biologic a patient is on doesn’t seem to matter.
"I think this entire area needs more study," Dr. Kremer said in an interview. For example, "are there biomarkers associated with the ability to withdraw? I don’t believe we know much about who can or should withdraw." Once withdrawal occurs, he recommended careful follow-up to detect a flare quickly, and restarting the biologic if even a mild flare occurs.
Biologic withdrawal "is really more investigational" right now, said Dr. Eric L. Matteson, professor and chairman of rheumatology at the Mayo Clinic in Rochester, Minn. "No guideline establishes it as standard of practice. I like to see patients in full remission for a year before considering such a move," he said in an interview. Withdrawal depends on whether the RA is well controlled and not on whether treatment started on early or established RA, he added; nor did he think that a flare after withdrawal precludes future withdrawal attempts as long as the patient returns to a durable, full remission. But Dr. Matteson did caution about also considering extra-articular disease like vasculitis or iritis that may be active even when a patient’s joints are not. "Any evidence of recurrent disease should cause the patient and physician to consider ramping the therapy back up."
Like others, Dr. Matteson highlighted the lingering unknowns about biologic withdrawal that keep it from being standard practice. "We don’t know whether the biologic or synthetic DMARD should get withdrawn first. We don’t have a great handle on what biomarkers to use to help decide if there is subclinical disease activity that necessitates reimplementation of the biologic. We don’t know which patients may violently flare following withdrawal and which might not. We also don’t know if retreatment of the disease is as good when a biologic is withdrawn and then restarted. Finally, I think we overestimate the percent of our patients who are actually in remission or a low-disease-activity state and underestimate who really should continue their medications."
The STARA trial
Dr. Weinstein and his associates recently planned a U.S.-based trial that has come close to launching to address several of these issues, the STARA (Stopping TNF-Alpha Inhibitors in Rheumatoid Arthritis) trial.
"One aspect of STARA is to determine whether there is a profile of clinical, imaging, and laboratory factors that will reliably distinguish patients who will flare from those who will remain in remission" following withdrawal of a biologic DMARD, said Dr. Weinstein, STARA’s lead investigator and also a professor of medicine at Georgetown University in Washington. "Another aim is to find predictors of good candidates for withdrawal. The advantage of STARA is patients are drawn from real-world practice and not from a clinical trial." Dr. Weinstein faulted some of the published studies of biologic withdrawal, such as OPTIMA and PRESERVE, because they included trial patients exclusively and not patients managed in routine practice.
STARA’s design uses a sudden, full withdrawal of the biologic to allow a standardized approach to patients who could enter the study on etanercept, adalimumab, or infliximab (Remicade). For routine practice, gradual withdrawal is more common, though there is no evidence this produces better long-term outcomes. An important withdrawal question that STARA won’t address is: Which is the better drug to remove, the biologic or the synthetic DMARD? In most cases, the more expensive biologic is the patient’s choice, but ideally this issue should be addressed in a randomized trial, Dr. Weinstein said.
But as of late March, STARA’s status was in doubt, as anticipated funding was withdrawn. If STARA isn’t run, Dr. Weinstein predicts that attempts to cut biologics from dual regimens will continue and likely expand, but with unknown implications for long-term safety that he believes can only be addressed in a prospective, randomized trial.
Dr. Weinstein said that he had no relevant disclosures. Dr. Matteson had no disclosures. Dr. Kremer has received research support and been a consultant to more than 10 drug companies. Dr. Kavanaugh has received research support from more than 10 drug companies.
On Twitter @mitchelzoler
