Treat-to-Target Early for Real-World Remission

Use of a strict, treat-to-target strategy enabled nearly half of patients with newly diagnosed rheumatoid arthritis to achieve remission within 6 months.

These "excellent results" mean that, while it is assumed that the efficacy seen in clinical trials is not repeatable in the real world, "achievement of remission in very-early RA in daily clinical practice using a treat-to-target strategy is a realistic goal," investigators reported in the October issue of Arthritis and Rheumatism.

Marloes Vermeer of the University of Twente, Enschede, the Netherlands, and her colleagues, looked at 534 consecutive patients with a clinical diagnosis of very early rheumatoid arthritis (RA) who were enrolled in the DREAM (Dutch Rheumatoid Arthritis Monitoring) study, beginning in January 2006 (Arthritis Rheum. 2011;63:2865-72).

All patients were at least 18 years of age and their diagnosis of RA had been made within 1 year or less. They also all had symptom duration of 1 year or less; a disease activity score in 28 joints (DAS28) of 2.6 or greater; and no previous treatment with disease-modifying antirheumatic drugs (DMARDs) or prednisolone.

Overall, 62.4% of patients were female, with a mean age of 58.6 years and a mean DAS28 of 5.0. The average symptom duration was just 14 weeks.

Patients were evaluated at weeks 0, 8, 12, 20, 24, 36, 52, and every 3 months thereafter. The target DAS28 score was less than 2.6 (remission), and treatment followed a precise regimen, dictated by the DAS28.

All patients initially were prescribed methotrexate 15 mg/week, given orally.

At week 8, if the treatment target was not met, patients were escalated to a dose of 25 mg/week.

At week 12, if the target was still not met, the investigators added oral sulfasalazine 2,000 mg/day; at week 20, the sulfasalazine dose was increased to 3,000 mg/day.

By week 24, if the DAS28 was greater than or equal to 3.2 (per Dutch reimbursement regulations), the investigators substituted subcutaneous adalimumab 40 mg every 2 weeks instead of sulfasalazine (while still maintaining daily methotrexate).

If by 36 weeks the DAS28 was still greater than 2.6, administration of the adalimumab dose was increased to once per week.

Finally, scores above or equal to 3.2 at week 52 (1 year) were treated with subcutaneous etanercept 50 mg/week instead of adalimumab. At 1 year and 3 months, patients with scores above 3.2 received intravenous infliximab 3 mg/kg every 8 weeks instead of etanercept; 3 months later, scores greater than 2.6 increased that infliximab dose to every 4 weeks.

Once the patient’s RA activity had lessened to the point that target DAS28 score of less than 2.6 was reached and maintained for at least 6 months, "medication was gradually stepped down and eventually discontinued," wrote the authors. Flares were treated according to the "most recently effective medication or medication dosage restarted."

Researchers found that among the 491 patients for whom 6-month follow-up data were available, 47% achieved the goal of DAS28 remission.

"Low, moderate, and high disease activity was observed in 19.4%, 29.1%, and 4.5% of the patients, respectively," wrote Ms. Vermeer.

By 12 months, among the 389 remaining patients with adequate follow-up data, 58.1% had achieved DAS28 remission.

"Disease activity was low in 14.7%, moderate in 24.9%, and high in 2.3% of patients," added the investigators.

Results also were positive according to the European League Against Rheumatism (EULAR) response criteria, with a good response observed in 57.6% of patients at 6 months, a moderate response in 28.3%, and no response in 14.1%.

"After 12 months, good, moderate, and no responses were observed in 67.9%, 23.9%, and 8.2% of the patients," respectively, according to the EULAR criteria.

Additionally, the median time to DAS28 remission was found to be 25.3 weeks.

The authors conceded several limitations to their study. For one, they pointed out that follow-up data for only 1 year are available at present.

"Long-term follow-up of the DREAM remission induction cohort is ongoing, which is critical for examining whether remission is sustained and for evaluating the long-term effects on radiographic progression and functional ability," they wrote.

Moreover, "our results reflect the effects of only one medication strategy; no comparator was included," they added. "Other strategies will be evaluated in forthcoming cohorts."

Nevertheless, "our results underscore the importance of immediate treatment after diagnosis," they concluded.

"When remission is accepted as the therapeutic goal of RA, it is evident that disease management should include monitoring of disease activity and adjustment of therapy accordingly."

Ms. Vermeer disclosed that her work was supported by an unrestricted educational grant from Abbott. The investigators made no additional disclosures.

Use of a strict, treat-to-target strategy enabled nearly half of patients with newly diagnosed rheumatoid arthritis to achieve remission within 6 months.

These "excellent results" mean that, while it is assumed that the efficacy seen in clinical trials is not repeatable in the real world, "achievement of remission in very-early RA in daily clinical practice using a treat-to-target strategy is a realistic goal," investigators reported in the October issue of Arthritis and Rheumatism.

Marloes Vermeer of the University of Twente, Enschede, the Netherlands, and her colleagues, looked at 534 consecutive patients with a clinical diagnosis of very early rheumatoid arthritis (RA) who were enrolled in the DREAM (Dutch Rheumatoid Arthritis Monitoring) study, beginning in January 2006 (Arthritis Rheum. 2011;63:2865-72).

All patients were at least 18 years of age and their diagnosis of RA had been made within 1 year or less. They also all had symptom duration of 1 year or less; a disease activity score in 28 joints (DAS28) of 2.6 or greater; and no previous treatment with disease-modifying antirheumatic drugs (DMARDs) or prednisolone.

Overall, 62.4% of patients were female, with a mean age of 58.6 years and a mean DAS28 of 5.0. The average symptom duration was just 14 weeks.

Patients were evaluated at weeks 0, 8, 12, 20, 24, 36, 52, and every 3 months thereafter. The target DAS28 score was less than 2.6 (remission), and treatment followed a precise regimen, dictated by the DAS28.

All patients initially were prescribed methotrexate 15 mg/week, given orally.

At week 8, if the treatment target was not met, patients were escalated to a dose of 25 mg/week.

At week 12, if the target was still not met, the investigators added oral sulfasalazine 2,000 mg/day; at week 20, the sulfasalazine dose was increased to 3,000 mg/day.

By week 24, if the DAS28 was greater than or equal to 3.2 (per Dutch reimbursement regulations), the investigators substituted subcutaneous adalimumab 40 mg every 2 weeks instead of sulfasalazine (while still maintaining daily methotrexate).

If by 36 weeks the DAS28 was still greater than 2.6, administration of the adalimumab dose was increased to once per week.

Finally, scores above or equal to 3.2 at week 52 (1 year) were treated with subcutaneous etanercept 50 mg/week instead of adalimumab. At 1 year and 3 months, patients with scores above 3.2 received intravenous infliximab 3 mg/kg every 8 weeks instead of etanercept; 3 months later, scores greater than 2.6 increased that infliximab dose to every 4 weeks.

Once the patient’s RA activity had lessened to the point that target DAS28 score of less than 2.6 was reached and maintained for at least 6 months, "medication was gradually stepped down and eventually discontinued," wrote the authors. Flares were treated according to the "most recently effective medication or medication dosage restarted."

Researchers found that among the 491 patients for whom 6-month follow-up data were available, 47% achieved the goal of DAS28 remission.

"Low, moderate, and high disease activity was observed in 19.4%, 29.1%, and 4.5% of the patients, respectively," wrote Ms. Vermeer.

By 12 months, among the 389 remaining patients with adequate follow-up data, 58.1% had achieved DAS28 remission.

"Disease activity was low in 14.7%, moderate in 24.9%, and high in 2.3% of patients," added the investigators.

Results also were positive according to the European League Against Rheumatism (EULAR) response criteria, with a good response observed in 57.6% of patients at 6 months, a moderate response in 28.3%, and no response in 14.1%.

"After 12 months, good, moderate, and no responses were observed in 67.9%, 23.9%, and 8.2% of the patients," respectively, according to the EULAR criteria.

Additionally, the median time to DAS28 remission was found to be 25.3 weeks.

The authors conceded several limitations to their study. For one, they pointed out that follow-up data for only 1 year are available at present.

"Long-term follow-up of the DREAM remission induction cohort is ongoing, which is critical for examining whether remission is sustained and for evaluating the long-term effects on radiographic progression and functional ability," they wrote.

Moreover, "our results reflect the effects of only one medication strategy; no comparator was included," they added. "Other strategies will be evaluated in forthcoming cohorts."

Nevertheless, "our results underscore the importance of immediate treatment after diagnosis," they concluded.

"When remission is accepted as the therapeutic goal of RA, it is evident that disease management should include monitoring of disease activity and adjustment of therapy accordingly."

Ms. Vermeer disclosed that her work was supported by an unrestricted educational grant from Abbott. The investigators made no additional disclosures.

Use of a strict, treat-to-target strategy enabled nearly half of patients with newly diagnosed rheumatoid arthritis to achieve remission within 6 months.

These "excellent results" mean that, while it is assumed that the efficacy seen in clinical trials is not repeatable in the real world, "achievement of remission in very-early RA in daily clinical practice using a treat-to-target strategy is a realistic goal," investigators reported in the October issue of Arthritis and Rheumatism.

Marloes Vermeer of the University of Twente, Enschede, the Netherlands, and her colleagues, looked at 534 consecutive patients with a clinical diagnosis of very early rheumatoid arthritis (RA) who were enrolled in the DREAM (Dutch Rheumatoid Arthritis Monitoring) study, beginning in January 2006 (Arthritis Rheum. 2011;63:2865-72).

All patients were at least 18 years of age and their diagnosis of RA had been made within 1 year or less. They also all had symptom duration of 1 year or less; a disease activity score in 28 joints (DAS28) of 2.6 or greater; and no previous treatment with disease-modifying antirheumatic drugs (DMARDs) or prednisolone.

Overall, 62.4% of patients were female, with a mean age of 58.6 years and a mean DAS28 of 5.0. The average symptom duration was just 14 weeks.

Patients were evaluated at weeks 0, 8, 12, 20, 24, 36, 52, and every 3 months thereafter. The target DAS28 score was less than 2.6 (remission), and treatment followed a precise regimen, dictated by the DAS28.

All patients initially were prescribed methotrexate 15 mg/week, given orally.

At week 8, if the treatment target was not met, patients were escalated to a dose of 25 mg/week.

At week 12, if the target was still not met, the investigators added oral sulfasalazine 2,000 mg/day; at week 20, the sulfasalazine dose was increased to 3,000 mg/day.

By week 24, if the DAS28 was greater than or equal to 3.2 (per Dutch reimbursement regulations), the investigators substituted subcutaneous adalimumab 40 mg every 2 weeks instead of sulfasalazine (while still maintaining daily methotrexate).

If by 36 weeks the DAS28 was still greater than 2.6, administration of the adalimumab dose was increased to once per week.

Finally, scores above or equal to 3.2 at week 52 (1 year) were treated with subcutaneous etanercept 50 mg/week instead of adalimumab. At 1 year and 3 months, patients with scores above 3.2 received intravenous infliximab 3 mg/kg every 8 weeks instead of etanercept; 3 months later, scores greater than 2.6 increased that infliximab dose to every 4 weeks.

Once the patient’s RA activity had lessened to the point that target DAS28 score of less than 2.6 was reached and maintained for at least 6 months, "medication was gradually stepped down and eventually discontinued," wrote the authors. Flares were treated according to the "most recently effective medication or medication dosage restarted."

Researchers found that among the 491 patients for whom 6-month follow-up data were available, 47% achieved the goal of DAS28 remission.

"Low, moderate, and high disease activity was observed in 19.4%, 29.1%, and 4.5% of the patients, respectively," wrote Ms. Vermeer.

By 12 months, among the 389 remaining patients with adequate follow-up data, 58.1% had achieved DAS28 remission.

"Disease activity was low in 14.7%, moderate in 24.9%, and high in 2.3% of patients," added the investigators.

Results also were positive according to the European League Against Rheumatism (EULAR) response criteria, with a good response observed in 57.6% of patients at 6 months, a moderate response in 28.3%, and no response in 14.1%.

"After 12 months, good, moderate, and no responses were observed in 67.9%, 23.9%, and 8.2% of the patients," respectively, according to the EULAR criteria.

Additionally, the median time to DAS28 remission was found to be 25.3 weeks.

The authors conceded several limitations to their study. For one, they pointed out that follow-up data for only 1 year are available at present.

"Long-term follow-up of the DREAM remission induction cohort is ongoing, which is critical for examining whether remission is sustained and for evaluating the long-term effects on radiographic progression and functional ability," they wrote.

Moreover, "our results reflect the effects of only one medication strategy; no comparator was included," they added. "Other strategies will be evaluated in forthcoming cohorts."

Nevertheless, "our results underscore the importance of immediate treatment after diagnosis," they concluded.

"When remission is accepted as the therapeutic goal of RA, it is evident that disease management should include monitoring of disease activity and adjustment of therapy accordingly."

Ms. Vermeer disclosed that her work was supported by an unrestricted educational grant from Abbott. The investigators made no additional disclosures.