Small Study: Reduced Anti-TNF Dose Still Effective

BERLIN – Most patients with long-standing rheumatoid arthritis or other rheumatic diseases and in remission while on an anti–tumor necrosis factor drug could successfully undergo dose reduction and stay in remission, based on experience with 90 patients at one U.K. center.

In addition to maintaining a majority of patients on a reduced biologic regimen, a step that pleased patients, the program produced substantial cost savings, cutting drug costs in the unit by more than $400,000 during the course of 1 year, Dr. Jane Gibson said at the annual meeting of the European Congress of Rheumatology.

Out of 90 patients with rheumatoid arthritis (RA) or another rheumatic disease and in remission for more than a year and on a stable, standard regimen with etanercept or adalimumab, 68 (76%) successfully underwent a dosage reduction and remained in remission, said Dr. Gibson, head of the Fife Rheumatic Diseases Unit, part of the U.K. National Health Service serving the county of Fife in Scotland.

The sixteen patients who failed to stay in remission while on a reduced dosage of an anti–tumor necrosis factor (anti-TNF) drug were all successfully put back into remission with a corticosteroid injection and reinstitution of their prior treatment. Another six patients stopped their anti-TNF regimen for unrelated reasons during the period of the study, December 2010 to December 2011.

"These were patients with very long-standing disease, with some patients having RA for more than 40 years. The patients loved it; they felt it was a positive step. That was a big surprise because I thought that I’d have to persuade patients, but they thought it was great," Dr. Gibson said in an interview.

A regression analysis identified several factors significantly linked with an increased likelihood of patients’ successfully undergoing a dose reduction and remaining in remission. The strongest link was for concomitant treatment with methotrexate, according to Dr. Gibson and her associates. Patients who received methotrexate along with the anti-TNF drug had a substantially better rate of continued remission once the anti-TNF dosage dropped. Other statistically significant factors linked with successful dose reduction were concomitant treatment with any disease modifying anti-rheumatic drug (DMARD), and treatment with adalimumab (compared with treatment with etanercept). In addition, smoking history showed a strong trend toward a better rate of remission among never smokers or former smokers, but this did not reach statistical significance.

Dr. Gibson cautioned that any difference in the durability of remission on adalimumab compared with etanercept might result from the substantially shorter clinical half-lives of the two drugs. Etanercept has a half-life of 3-4 days, so cutting the dosage from the standard 50 mg subcutaneously once per week to 50 mg once every 2 weeks meant that patients scaled back to roughly four times the drug’s half-life. Thirteen of the 16 failed remissions occurred among patients switched to 50 mg etanercept every 2 weeks; among four patients scaled back to 50 mg etanercept administered every 10 days, none fell out of remission, Dr. Gibson said.

In contrast, adalimumab’s clinical half-life is about 14 days, so scaling back from the standard dosage of 40 mg subcutaneously every 2 weeks to the same amount given every 4 weeks meant that patients received the drug at intervals twice as long as the half-life. None of the 14 patients who received adalimumab every 4 weeks fell out of remission, and just two of 16 patients came out of remission when scaled back to a dosage of 40 mg adalimumab every 3 weeks.

Although concomitant methotrexate was the strongest predictor of success with scaled back dosing, only about half the patients in the Fife series were on methotrexate, and nearly a third were not on any concomitant DMARD, and so Dr. Gibson said she was unsure about any ironclad need to get patients on methotrexate or another DMARD before attempting to scale back the frequency of use of an anti-TNF agent. She said that she would attempt a small cut in anti-TNF dosage – to etanercept every 10 days or adalimumab every 3 weeks – even in patients not on a DMARD, especially if they were not current smokers, she said, although she would also frequently review these patients to watch for signs of a flare.

The premise of the approach is: "Why keep patients at the same dose? Why not see if we can adjust it?" she said.

The 84 rheumatic-disease patients who underwent an anti-TNF dose-adjustment included three-quarters with RA, with most other patients having psoriatic arthritis or ankylosing spondylitis. The average age was 57 years. Mean disease duration was more than 15 years. Their average time in continued remission at a reduced anti-TNF dosage was 11 months, with one patient followed for almost 3 years. Patients who fell out of remission tended to do so quickly, after an average of less than 4 months, and with only one patient taking longer than 5 months to fail.

Dr. Gibson said that she had no disclosures.

BERLIN – Most patients with long-standing rheumatoid arthritis or other rheumatic diseases and in remission while on an anti–tumor necrosis factor drug could successfully undergo dose reduction and stay in remission, based on experience with 90 patients at one U.K. center.

In addition to maintaining a majority of patients on a reduced biologic regimen, a step that pleased patients, the program produced substantial cost savings, cutting drug costs in the unit by more than $400,000 during the course of 1 year, Dr. Jane Gibson said at the annual meeting of the European Congress of Rheumatology.

Out of 90 patients with rheumatoid arthritis (RA) or another rheumatic disease and in remission for more than a year and on a stable, standard regimen with etanercept or adalimumab, 68 (76%) successfully underwent a dosage reduction and remained in remission, said Dr. Gibson, head of the Fife Rheumatic Diseases Unit, part of the U.K. National Health Service serving the county of Fife in Scotland.

The sixteen patients who failed to stay in remission while on a reduced dosage of an anti–tumor necrosis factor (anti-TNF) drug were all successfully put back into remission with a corticosteroid injection and reinstitution of their prior treatment. Another six patients stopped their anti-TNF regimen for unrelated reasons during the period of the study, December 2010 to December 2011.

"These were patients with very long-standing disease, with some patients having RA for more than 40 years. The patients loved it; they felt it was a positive step. That was a big surprise because I thought that I’d have to persuade patients, but they thought it was great," Dr. Gibson said in an interview.

A regression analysis identified several factors significantly linked with an increased likelihood of patients’ successfully undergoing a dose reduction and remaining in remission. The strongest link was for concomitant treatment with methotrexate, according to Dr. Gibson and her associates. Patients who received methotrexate along with the anti-TNF drug had a substantially better rate of continued remission once the anti-TNF dosage dropped. Other statistically significant factors linked with successful dose reduction were concomitant treatment with any disease modifying anti-rheumatic drug (DMARD), and treatment with adalimumab (compared with treatment with etanercept). In addition, smoking history showed a strong trend toward a better rate of remission among never smokers or former smokers, but this did not reach statistical significance.

Dr. Gibson cautioned that any difference in the durability of remission on adalimumab compared with etanercept might result from the substantially shorter clinical half-lives of the two drugs. Etanercept has a half-life of 3-4 days, so cutting the dosage from the standard 50 mg subcutaneously once per week to 50 mg once every 2 weeks meant that patients scaled back to roughly four times the drug’s half-life. Thirteen of the 16 failed remissions occurred among patients switched to 50 mg etanercept every 2 weeks; among four patients scaled back to 50 mg etanercept administered every 10 days, none fell out of remission, Dr. Gibson said.

In contrast, adalimumab’s clinical half-life is about 14 days, so scaling back from the standard dosage of 40 mg subcutaneously every 2 weeks to the same amount given every 4 weeks meant that patients received the drug at intervals twice as long as the half-life. None of the 14 patients who received adalimumab every 4 weeks fell out of remission, and just two of 16 patients came out of remission when scaled back to a dosage of 40 mg adalimumab every 3 weeks.

Although concomitant methotrexate was the strongest predictor of success with scaled back dosing, only about half the patients in the Fife series were on methotrexate, and nearly a third were not on any concomitant DMARD, and so Dr. Gibson said she was unsure about any ironclad need to get patients on methotrexate or another DMARD before attempting to scale back the frequency of use of an anti-TNF agent. She said that she would attempt a small cut in anti-TNF dosage – to etanercept every 10 days or adalimumab every 3 weeks – even in patients not on a DMARD, especially if they were not current smokers, she said, although she would also frequently review these patients to watch for signs of a flare.

The premise of the approach is: "Why keep patients at the same dose? Why not see if we can adjust it?" she said.

The 84 rheumatic-disease patients who underwent an anti-TNF dose-adjustment included three-quarters with RA, with most other patients having psoriatic arthritis or ankylosing spondylitis. The average age was 57 years. Mean disease duration was more than 15 years. Their average time in continued remission at a reduced anti-TNF dosage was 11 months, with one patient followed for almost 3 years. Patients who fell out of remission tended to do so quickly, after an average of less than 4 months, and with only one patient taking longer than 5 months to fail.

Dr. Gibson said that she had no disclosures.

BERLIN – Most patients with long-standing rheumatoid arthritis or other rheumatic diseases and in remission while on an anti–tumor necrosis factor drug could successfully undergo dose reduction and stay in remission, based on experience with 90 patients at one U.K. center.

In addition to maintaining a majority of patients on a reduced biologic regimen, a step that pleased patients, the program produced substantial cost savings, cutting drug costs in the unit by more than $400,000 during the course of 1 year, Dr. Jane Gibson said at the annual meeting of the European Congress of Rheumatology.

Out of 90 patients with rheumatoid arthritis (RA) or another rheumatic disease and in remission for more than a year and on a stable, standard regimen with etanercept or adalimumab, 68 (76%) successfully underwent a dosage reduction and remained in remission, said Dr. Gibson, head of the Fife Rheumatic Diseases Unit, part of the U.K. National Health Service serving the county of Fife in Scotland.

The sixteen patients who failed to stay in remission while on a reduced dosage of an anti–tumor necrosis factor (anti-TNF) drug were all successfully put back into remission with a corticosteroid injection and reinstitution of their prior treatment. Another six patients stopped their anti-TNF regimen for unrelated reasons during the period of the study, December 2010 to December 2011.

"These were patients with very long-standing disease, with some patients having RA for more than 40 years. The patients loved it; they felt it was a positive step. That was a big surprise because I thought that I’d have to persuade patients, but they thought it was great," Dr. Gibson said in an interview.

A regression analysis identified several factors significantly linked with an increased likelihood of patients’ successfully undergoing a dose reduction and remaining in remission. The strongest link was for concomitant treatment with methotrexate, according to Dr. Gibson and her associates. Patients who received methotrexate along with the anti-TNF drug had a substantially better rate of continued remission once the anti-TNF dosage dropped. Other statistically significant factors linked with successful dose reduction were concomitant treatment with any disease modifying anti-rheumatic drug (DMARD), and treatment with adalimumab (compared with treatment with etanercept). In addition, smoking history showed a strong trend toward a better rate of remission among never smokers or former smokers, but this did not reach statistical significance.

Dr. Gibson cautioned that any difference in the durability of remission on adalimumab compared with etanercept might result from the substantially shorter clinical half-lives of the two drugs. Etanercept has a half-life of 3-4 days, so cutting the dosage from the standard 50 mg subcutaneously once per week to 50 mg once every 2 weeks meant that patients scaled back to roughly four times the drug’s half-life. Thirteen of the 16 failed remissions occurred among patients switched to 50 mg etanercept every 2 weeks; among four patients scaled back to 50 mg etanercept administered every 10 days, none fell out of remission, Dr. Gibson said.

In contrast, adalimumab’s clinical half-life is about 14 days, so scaling back from the standard dosage of 40 mg subcutaneously every 2 weeks to the same amount given every 4 weeks meant that patients received the drug at intervals twice as long as the half-life. None of the 14 patients who received adalimumab every 4 weeks fell out of remission, and just two of 16 patients came out of remission when scaled back to a dosage of 40 mg adalimumab every 3 weeks.

Although concomitant methotrexate was the strongest predictor of success with scaled back dosing, only about half the patients in the Fife series were on methotrexate, and nearly a third were not on any concomitant DMARD, and so Dr. Gibson said she was unsure about any ironclad need to get patients on methotrexate or another DMARD before attempting to scale back the frequency of use of an anti-TNF agent. She said that she would attempt a small cut in anti-TNF dosage – to etanercept every 10 days or adalimumab every 3 weeks – even in patients not on a DMARD, especially if they were not current smokers, she said, although she would also frequently review these patients to watch for signs of a flare.

The premise of the approach is: "Why keep patients at the same dose? Why not see if we can adjust it?" she said.

The 84 rheumatic-disease patients who underwent an anti-TNF dose-adjustment included three-quarters with RA, with most other patients having psoriatic arthritis or ankylosing spondylitis. The average age was 57 years. Mean disease duration was more than 15 years. Their average time in continued remission at a reduced anti-TNF dosage was 11 months, with one patient followed for almost 3 years. Patients who fell out of remission tended to do so quickly, after an average of less than 4 months, and with only one patient taking longer than 5 months to fail.

Dr. Gibson said that she had no disclosures.