Given Time, the First Biologic Is Likely to Work

NEW YORK — Prescribing errors, such as premature withdrawal of a biologic agent once remission is achieved and hasty switching of agents, can undermine optimum results with biologics in the management of rheumatoid arthritis, according to Dr. Yusuf Yazici.

For instance, results from the BEST (Behandel Strategieen) trial (Ann. Rheum. Dis. 2009;68[suppl. 3]:544) showed that if patients who achieved remission with biologic therapy stopped that therapy, within 2 years 54% (62/115) stayed in drug-free remission, said Dr. Yazici, a rheumatologist who is director of the Seligman Center for Advanced Therapeutics and Behcet's Syndrome Evaluation, Treatment and Research Center at the New York University Hospital for Joint Diseases. The remaining patients saw their disease flare, but while about three-quarters of those (39/53 or 34% of the original group) were brought back into remission within 6 months, about one-quarter (14/53 or 12% of the original group of 115) did not achieve remission again. “That number is too large,” said Dr. Yazici.

“Just as we would not consider stopping treatment for diabetes or hypertension, this chronic disease treatment approach should also be considered in patients with RA,” said Dr. Yazici. He advised against tapering or stopping the combination of medications that was required to achieve remission unless there is a safety concern.

Another problem that Dr. Yazici has noticed is failure to allow enough time for one tumor necrosis factor–inhibiting (TNFi) biologic to take effect before switching to another biologic. Common reasons for switching cited are inefficacy or adverse events.

In a retrospective analysis of an insurance claims database of 9,075 patients with RA who started a TNFi agent during the period 2000-2005, Dr. Yazici saw more frequent changes among different TNFi agents and shorter duration of treatment before change, as time progressed. The use of a first-prescribed biologic medication dropped by about 45% after the first year and 70% after the second year; by 3 years, only a small percentage remained on the same therapy. In this study, infliximab had the highest duration of continuation, about 50% at 2 years. After adalimumab was introduced into the market, a dramatic drop in time to switch was observed, from a mean of 454 days to 237 days among TNFi agents (J. Rheumatol. 2009;36:907-13). “The more biologics we have, the faster we switch, it seems,” commented Dr. Yazici.

Dr. Yazici also cited data from the DANBIO registry, a nationwide Danish registry of patients with RA, in which 2,326 patients were observed after initiation of biologic therapy.

After 4 years, 56% were still taking etanercept, 52% were still on adalimumab, and 41% remained on infliximab. Drug withdrawal was primarily attributed to adverse effects and secondarily to lack of efficacy (Arthritis Rheum. 2010;62:22-32).

Published data on etanercept, adalimumab, infliximab, and abatacept suggest no real differences in efficacy in most patients who use them, said Dr. Yazici. Data from registries tend to show no preference for one over another. He suggested that physicians allow at least a 3- to 6-month trial period before switching biologic agents.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb, Celgene, Genentech, Roche, and UCB.

NEW YORK — Prescribing errors, such as premature withdrawal of a biologic agent once remission is achieved and hasty switching of agents, can undermine optimum results with biologics in the management of rheumatoid arthritis, according to Dr. Yusuf Yazici.

For instance, results from the BEST (Behandel Strategieen) trial (Ann. Rheum. Dis. 2009;68[suppl. 3]:544) showed that if patients who achieved remission with biologic therapy stopped that therapy, within 2 years 54% (62/115) stayed in drug-free remission, said Dr. Yazici, a rheumatologist who is director of the Seligman Center for Advanced Therapeutics and Behcet's Syndrome Evaluation, Treatment and Research Center at the New York University Hospital for Joint Diseases. The remaining patients saw their disease flare, but while about three-quarters of those (39/53 or 34% of the original group) were brought back into remission within 6 months, about one-quarter (14/53 or 12% of the original group of 115) did not achieve remission again. “That number is too large,” said Dr. Yazici.

“Just as we would not consider stopping treatment for diabetes or hypertension, this chronic disease treatment approach should also be considered in patients with RA,” said Dr. Yazici. He advised against tapering or stopping the combination of medications that was required to achieve remission unless there is a safety concern.

Another problem that Dr. Yazici has noticed is failure to allow enough time for one tumor necrosis factor–inhibiting (TNFi) biologic to take effect before switching to another biologic. Common reasons for switching cited are inefficacy or adverse events.

In a retrospective analysis of an insurance claims database of 9,075 patients with RA who started a TNFi agent during the period 2000-2005, Dr. Yazici saw more frequent changes among different TNFi agents and shorter duration of treatment before change, as time progressed. The use of a first-prescribed biologic medication dropped by about 45% after the first year and 70% after the second year; by 3 years, only a small percentage remained on the same therapy. In this study, infliximab had the highest duration of continuation, about 50% at 2 years. After adalimumab was introduced into the market, a dramatic drop in time to switch was observed, from a mean of 454 days to 237 days among TNFi agents (J. Rheumatol. 2009;36:907-13). “The more biologics we have, the faster we switch, it seems,” commented Dr. Yazici.

Dr. Yazici also cited data from the DANBIO registry, a nationwide Danish registry of patients with RA, in which 2,326 patients were observed after initiation of biologic therapy.

After 4 years, 56% were still taking etanercept, 52% were still on adalimumab, and 41% remained on infliximab. Drug withdrawal was primarily attributed to adverse effects and secondarily to lack of efficacy (Arthritis Rheum. 2010;62:22-32).

Published data on etanercept, adalimumab, infliximab, and abatacept suggest no real differences in efficacy in most patients who use them, said Dr. Yazici. Data from registries tend to show no preference for one over another. He suggested that physicians allow at least a 3- to 6-month trial period before switching biologic agents.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb, Celgene, Genentech, Roche, and UCB.

NEW YORK — Prescribing errors, such as premature withdrawal of a biologic agent once remission is achieved and hasty switching of agents, can undermine optimum results with biologics in the management of rheumatoid arthritis, according to Dr. Yusuf Yazici.

For instance, results from the BEST (Behandel Strategieen) trial (Ann. Rheum. Dis. 2009;68[suppl. 3]:544) showed that if patients who achieved remission with biologic therapy stopped that therapy, within 2 years 54% (62/115) stayed in drug-free remission, said Dr. Yazici, a rheumatologist who is director of the Seligman Center for Advanced Therapeutics and Behcet's Syndrome Evaluation, Treatment and Research Center at the New York University Hospital for Joint Diseases. The remaining patients saw their disease flare, but while about three-quarters of those (39/53 or 34% of the original group) were brought back into remission within 6 months, about one-quarter (14/53 or 12% of the original group of 115) did not achieve remission again. “That number is too large,” said Dr. Yazici.

“Just as we would not consider stopping treatment for diabetes or hypertension, this chronic disease treatment approach should also be considered in patients with RA,” said Dr. Yazici. He advised against tapering or stopping the combination of medications that was required to achieve remission unless there is a safety concern.

Another problem that Dr. Yazici has noticed is failure to allow enough time for one tumor necrosis factor–inhibiting (TNFi) biologic to take effect before switching to another biologic. Common reasons for switching cited are inefficacy or adverse events.

In a retrospective analysis of an insurance claims database of 9,075 patients with RA who started a TNFi agent during the period 2000-2005, Dr. Yazici saw more frequent changes among different TNFi agents and shorter duration of treatment before change, as time progressed. The use of a first-prescribed biologic medication dropped by about 45% after the first year and 70% after the second year; by 3 years, only a small percentage remained on the same therapy. In this study, infliximab had the highest duration of continuation, about 50% at 2 years. After adalimumab was introduced into the market, a dramatic drop in time to switch was observed, from a mean of 454 days to 237 days among TNFi agents (J. Rheumatol. 2009;36:907-13). “The more biologics we have, the faster we switch, it seems,” commented Dr. Yazici.

Dr. Yazici also cited data from the DANBIO registry, a nationwide Danish registry of patients with RA, in which 2,326 patients were observed after initiation of biologic therapy.

After 4 years, 56% were still taking etanercept, 52% were still on adalimumab, and 41% remained on infliximab. Drug withdrawal was primarily attributed to adverse effects and secondarily to lack of efficacy (Arthritis Rheum. 2010;62:22-32).

Published data on etanercept, adalimumab, infliximab, and abatacept suggest no real differences in efficacy in most patients who use them, said Dr. Yazici. Data from registries tend to show no preference for one over another. He suggested that physicians allow at least a 3- to 6-month trial period before switching biologic agents.

Dr. Yazici serves as a consultant to Bristol-Myers Squibb, Celgene, Genentech, Roche, and UCB.