Delaying Adalimumab Tx Impairs Long-Term Response

BERLIN – Delaying treatment of long-standing rheumatoid arthritis with adalimumab by 1 year leads to greater joint space narrowing 10 years later.

"This analysis demonstrates the cost of delay," remarked Dr. Edward Keystone, professor of medicine at the University of Toronto and lead investigator on the study. "Allowing a patient to have active disease a year longer is taking a toll on never catching up on quality of life, never catching up on radiographic outcome, and never catching up with persistent active disease."

These findings come from the final analysis of results of the DEO19 trial, which compared patients on methotrexate plus either adalimumab or placebo for 1 year and followed up with all patients receiving active drug for a further 9 years.

"Earlier treatment is better. You are treating to prevent irreversible joint damage, so over time, you want a patient’s quality of life to remain the same," Dr. Keystone said at the annual European Congress of Rheumatology.

Trial DEO19 was a 1-year, randomized, double-blind, placebo-controlled study of adalimumab in patients inadequately controlled on methotrexate. Patients with moderate to severely active disease were randomly assigned to receiving either adalimumab at 40 mg every other week (209 patients), adalimumab 20 mg every week (212), or placebo (200). All patients continued on methotrexate.

After the initial 1-year blinded stage, all patents were eligible to receive open-label adalimumab 40 mg for the next 9 years. Of the initial entrants, 457 went through to the open-label phase, and 202 completed the 9-year extension. Average disease duration upon entry was 11 years.

"Even at 11 years’ duration of RA, when they all have active disease, you can improve patients’ signs and symptoms when they receive adalimumab," pointed out Dr. Keystone. "It is possible to maintain quality of life and actually prevent radiographic progression or stabilize it and show minimal progression after treatment."

The 10-year follow-up data showed that 63.5% of completers reached an American College of Rheumatology 50; 48.4% reached an ACR 70 and 17.7% an ACR 90. A disease activity score 28 of less than 3.2 was achieved by 73.6% of patients, and a Health Assessment Questionnaire less than 0.5 was achieved by 42.8%.

Mean swollen joint count (SJC) persisted in patients who were originally treated with placebo as opposed to adalimumab, with a SJC of just under 5 at 10 years in the group given either dose of adalimumab at year 1 versus approximately 7.5 in the year 1 placebo group.

Furthermore, 30.3% of patients who received adalimumab originally achieved comprehensive disease control – indicated by a DAS28 C-reactive protein of less than 3.2 – at year 10 vs. 11.3% of those on placebo.

"These results show that one in three people who started on adalimumab ended up in a comprehensive disease state, that is no disability, no radiographic progression, and clinical remission," reported Dr. Keystone.

"I treat patients with 10 years of active disease and I improve them to only a few swollen joints, but I treat them at 11 years and I still can’t get them down to the level I want."

"For me, that is a surprise," said Dr. Keystone. "I thought the placebo patients would eventually reach the same level as the others who started a year earlier, but that didn’t happen."

Dr. Keystone noted that joint space narrowing continued over time as seen by the change in Sharp score over 10 years. "This is accounted for not by erosions, but by the change in joint space narrowing," Dr. Keystone noted.

Radiographic damage was assessed using the modified total Sharp score. Patients who initially received adalimumab in year 1 had significantly lower mean change in modified total Sharp score at year 10, compared with patients who initially received placebo plus methotrexate [0.7 (ADA-40) and 2.6 (ADA-20) vs. 6.2 on placebo (P = .002 and 0.01, respectively).

Dr. Keystone highlighted this dramatic increase in joint space narrowing. "Patients treated on placebo initially ended up with more joint space narrowing over that period of time."

He also pointed out that joint space narrowing decreases quality of life, in addition to patients’ work productivity and ability to stay at work or not.

"Every drug has side effects. Everyone has a different answer to this. I’d like to see a study that helps us decide when it is optimal to start these types of drugs. But 10 years is a long time to follow these patients- it’s a good study. I would start patients earlier but I would also like to see data on which patients to start."

Dr. Keystone disclosed financial relationships with Abbott, Amgen, AstraZeneca, Biotest, Bristol-Myers Squibb, Centocor, Genentech, Genzyme, Merck, Novartis, Nycomed, Pfizer, Roche, and UCB.

BERLIN – Delaying treatment of long-standing rheumatoid arthritis with adalimumab by 1 year leads to greater joint space narrowing 10 years later.

"This analysis demonstrates the cost of delay," remarked Dr. Edward Keystone, professor of medicine at the University of Toronto and lead investigator on the study. "Allowing a patient to have active disease a year longer is taking a toll on never catching up on quality of life, never catching up on radiographic outcome, and never catching up with persistent active disease."

These findings come from the final analysis of results of the DEO19 trial, which compared patients on methotrexate plus either adalimumab or placebo for 1 year and followed up with all patients receiving active drug for a further 9 years.

"Earlier treatment is better. You are treating to prevent irreversible joint damage, so over time, you want a patient’s quality of life to remain the same," Dr. Keystone said at the annual European Congress of Rheumatology.

Trial DEO19 was a 1-year, randomized, double-blind, placebo-controlled study of adalimumab in patients inadequately controlled on methotrexate. Patients with moderate to severely active disease were randomly assigned to receiving either adalimumab at 40 mg every other week (209 patients), adalimumab 20 mg every week (212), or placebo (200). All patients continued on methotrexate.

After the initial 1-year blinded stage, all patents were eligible to receive open-label adalimumab 40 mg for the next 9 years. Of the initial entrants, 457 went through to the open-label phase, and 202 completed the 9-year extension. Average disease duration upon entry was 11 years.

"Even at 11 years’ duration of RA, when they all have active disease, you can improve patients’ signs and symptoms when they receive adalimumab," pointed out Dr. Keystone. "It is possible to maintain quality of life and actually prevent radiographic progression or stabilize it and show minimal progression after treatment."

The 10-year follow-up data showed that 63.5% of completers reached an American College of Rheumatology 50; 48.4% reached an ACR 70 and 17.7% an ACR 90. A disease activity score 28 of less than 3.2 was achieved by 73.6% of patients, and a Health Assessment Questionnaire less than 0.5 was achieved by 42.8%.

Mean swollen joint count (SJC) persisted in patients who were originally treated with placebo as opposed to adalimumab, with a SJC of just under 5 at 10 years in the group given either dose of adalimumab at year 1 versus approximately 7.5 in the year 1 placebo group.

Furthermore, 30.3% of patients who received adalimumab originally achieved comprehensive disease control – indicated by a DAS28 C-reactive protein of less than 3.2 – at year 10 vs. 11.3% of those on placebo.

"These results show that one in three people who started on adalimumab ended up in a comprehensive disease state, that is no disability, no radiographic progression, and clinical remission," reported Dr. Keystone.

"I treat patients with 10 years of active disease and I improve them to only a few swollen joints, but I treat them at 11 years and I still can’t get them down to the level I want."

"For me, that is a surprise," said Dr. Keystone. "I thought the placebo patients would eventually reach the same level as the others who started a year earlier, but that didn’t happen."

Dr. Keystone noted that joint space narrowing continued over time as seen by the change in Sharp score over 10 years. "This is accounted for not by erosions, but by the change in joint space narrowing," Dr. Keystone noted.

Radiographic damage was assessed using the modified total Sharp score. Patients who initially received adalimumab in year 1 had significantly lower mean change in modified total Sharp score at year 10, compared with patients who initially received placebo plus methotrexate [0.7 (ADA-40) and 2.6 (ADA-20) vs. 6.2 on placebo (P = .002 and 0.01, respectively).

Dr. Keystone highlighted this dramatic increase in joint space narrowing. "Patients treated on placebo initially ended up with more joint space narrowing over that period of time."

He also pointed out that joint space narrowing decreases quality of life, in addition to patients’ work productivity and ability to stay at work or not.

"Every drug has side effects. Everyone has a different answer to this. I’d like to see a study that helps us decide when it is optimal to start these types of drugs. But 10 years is a long time to follow these patients- it’s a good study. I would start patients earlier but I would also like to see data on which patients to start."

Dr. Keystone disclosed financial relationships with Abbott, Amgen, AstraZeneca, Biotest, Bristol-Myers Squibb, Centocor, Genentech, Genzyme, Merck, Novartis, Nycomed, Pfizer, Roche, and UCB.

BERLIN – Delaying treatment of long-standing rheumatoid arthritis with adalimumab by 1 year leads to greater joint space narrowing 10 years later.

"This analysis demonstrates the cost of delay," remarked Dr. Edward Keystone, professor of medicine at the University of Toronto and lead investigator on the study. "Allowing a patient to have active disease a year longer is taking a toll on never catching up on quality of life, never catching up on radiographic outcome, and never catching up with persistent active disease."

These findings come from the final analysis of results of the DEO19 trial, which compared patients on methotrexate plus either adalimumab or placebo for 1 year and followed up with all patients receiving active drug for a further 9 years.

"Earlier treatment is better. You are treating to prevent irreversible joint damage, so over time, you want a patient’s quality of life to remain the same," Dr. Keystone said at the annual European Congress of Rheumatology.

Trial DEO19 was a 1-year, randomized, double-blind, placebo-controlled study of adalimumab in patients inadequately controlled on methotrexate. Patients with moderate to severely active disease were randomly assigned to receiving either adalimumab at 40 mg every other week (209 patients), adalimumab 20 mg every week (212), or placebo (200). All patients continued on methotrexate.

After the initial 1-year blinded stage, all patents were eligible to receive open-label adalimumab 40 mg for the next 9 years. Of the initial entrants, 457 went through to the open-label phase, and 202 completed the 9-year extension. Average disease duration upon entry was 11 years.

"Even at 11 years’ duration of RA, when they all have active disease, you can improve patients’ signs and symptoms when they receive adalimumab," pointed out Dr. Keystone. "It is possible to maintain quality of life and actually prevent radiographic progression or stabilize it and show minimal progression after treatment."

The 10-year follow-up data showed that 63.5% of completers reached an American College of Rheumatology 50; 48.4% reached an ACR 70 and 17.7% an ACR 90. A disease activity score 28 of less than 3.2 was achieved by 73.6% of patients, and a Health Assessment Questionnaire less than 0.5 was achieved by 42.8%.

Mean swollen joint count (SJC) persisted in patients who were originally treated with placebo as opposed to adalimumab, with a SJC of just under 5 at 10 years in the group given either dose of adalimumab at year 1 versus approximately 7.5 in the year 1 placebo group.

Furthermore, 30.3% of patients who received adalimumab originally achieved comprehensive disease control – indicated by a DAS28 C-reactive protein of less than 3.2 – at year 10 vs. 11.3% of those on placebo.

"These results show that one in three people who started on adalimumab ended up in a comprehensive disease state, that is no disability, no radiographic progression, and clinical remission," reported Dr. Keystone.

"I treat patients with 10 years of active disease and I improve them to only a few swollen joints, but I treat them at 11 years and I still can’t get them down to the level I want."

"For me, that is a surprise," said Dr. Keystone. "I thought the placebo patients would eventually reach the same level as the others who started a year earlier, but that didn’t happen."

Dr. Keystone noted that joint space narrowing continued over time as seen by the change in Sharp score over 10 years. "This is accounted for not by erosions, but by the change in joint space narrowing," Dr. Keystone noted.

Radiographic damage was assessed using the modified total Sharp score. Patients who initially received adalimumab in year 1 had significantly lower mean change in modified total Sharp score at year 10, compared with patients who initially received placebo plus methotrexate [0.7 (ADA-40) and 2.6 (ADA-20) vs. 6.2 on placebo (P = .002 and 0.01, respectively).

Dr. Keystone highlighted this dramatic increase in joint space narrowing. "Patients treated on placebo initially ended up with more joint space narrowing over that period of time."

He also pointed out that joint space narrowing decreases quality of life, in addition to patients’ work productivity and ability to stay at work or not.

"Every drug has side effects. Everyone has a different answer to this. I’d like to see a study that helps us decide when it is optimal to start these types of drugs. But 10 years is a long time to follow these patients- it’s a good study. I would start patients earlier but I would also like to see data on which patients to start."

Dr. Keystone disclosed financial relationships with Abbott, Amgen, AstraZeneca, Biotest, Bristol-Myers Squibb, Centocor, Genentech, Genzyme, Merck, Novartis, Nycomed, Pfizer, Roche, and UCB.