Repeat Rituximab Treatment As Soon as Symptoms Recur

BARCELONA — Patients with rheumatoid arthritis who are undergoing repeat courses of treatment with rituximab should begin re-treatment promptly once symptoms begin to recur, Dr. Philip J. Mease said at the annual European Congress of Rheumatology.

This conclusion emerged from analysis of the open-label extension phase of the Randomized Evaluation of Long-Term Efficacy of Rituximab in Rheumatoid Arthritis (REFLEX) trial, a double-blind, placebo-controlled multicenter study in which 298 patient initially received the active drug treatment.

All patients had failed at least one tumor necrosis factor blocker prior to beginning treatment with the B-cell-depleting agent. Those randomized to active treatment received two doses of rituximab, 1,000 mg, 2 weeks apart, plus stable doses of methotrexate.

Patients who achieved a 20% or greater improvement in swollen and tender joint counts during the 24-week blinded phase of the study were eligible to enter the open-label phase; 168 did so and had adequate follow-up for analysis 24 weeks after the second course of rituximab.

The four components of the 28-joint disease activity score (DAS28)—swollen joint count, tender joint count, erythrocyte sedimentation rate, and patient's global assessment—were assessed before each course of rituximab treatment, and every 4–8 weeks thereafter.

Mean DAS28 was 6.89 before the first course of rituximab and 6.12 before the second course, Dr. Mease wrote in a poster. The second course was administered at a median time of 43 weeks after the first course.

A generalized linear mixed model fit to all visits after the second course was used to evaluate the effects of various variables on DAS28, including pretrial patient and disease characteristics, DAS28 and Health Assessment Questionnaire at various times, and peripheral CD19+ B cell count before courses.

According to the model, DAS28 after the second course of treatment was independently increased by three factors: DAS28 before the second course, DAS28 at trial week 20, and Health Assessment Questionnaire at week 16.

Every 1 point that DAS28 was allowed to worsen before the second course of rituximab resulted in a 0.32-point higher DAS28 after the second course, according to Dr. Mease, who is a rheumatologist in Seattle.

Equally significant in the model but with the opposite effect on DAS28 was the peripheral CD19+ B-cell count before the second course: A count of at least 80 u 103/mL before the second course resulted in a 0.47-point lower DAS28 after the second course.

“The take-home message from this analysis is that in order to achieve the best DAS with a repeat course of rituximab, the preferable time for re-treatment is when the patient is starting to have resurgent symptoms,” Dr. Mease commented in an interview.

“On average, patient response lasts 6 months and at that point clinicians should start monitoring more diligently, looking for signs of disease activity. If the patient waits until 8 months for re-treatment, the resulting DAS won't be as good,” Dr. Mease added.

REFLEX was supported by Genentech, Biogen, and Roche. Dr. Mease has previously disclosed receiving consulting fees from Genentech and Biogen.

Symptom resurgence usually occurs about 6 months after ending the first course. DR. MEASE

BARCELONA — Patients with rheumatoid arthritis who are undergoing repeat courses of treatment with rituximab should begin re-treatment promptly once symptoms begin to recur, Dr. Philip J. Mease said at the annual European Congress of Rheumatology.

This conclusion emerged from analysis of the open-label extension phase of the Randomized Evaluation of Long-Term Efficacy of Rituximab in Rheumatoid Arthritis (REFLEX) trial, a double-blind, placebo-controlled multicenter study in which 298 patient initially received the active drug treatment.

All patients had failed at least one tumor necrosis factor blocker prior to beginning treatment with the B-cell-depleting agent. Those randomized to active treatment received two doses of rituximab, 1,000 mg, 2 weeks apart, plus stable doses of methotrexate.

Patients who achieved a 20% or greater improvement in swollen and tender joint counts during the 24-week blinded phase of the study were eligible to enter the open-label phase; 168 did so and had adequate follow-up for analysis 24 weeks after the second course of rituximab.

The four components of the 28-joint disease activity score (DAS28)—swollen joint count, tender joint count, erythrocyte sedimentation rate, and patient's global assessment—were assessed before each course of rituximab treatment, and every 4–8 weeks thereafter.

Mean DAS28 was 6.89 before the first course of rituximab and 6.12 before the second course, Dr. Mease wrote in a poster. The second course was administered at a median time of 43 weeks after the first course.

A generalized linear mixed model fit to all visits after the second course was used to evaluate the effects of various variables on DAS28, including pretrial patient and disease characteristics, DAS28 and Health Assessment Questionnaire at various times, and peripheral CD19+ B cell count before courses.

According to the model, DAS28 after the second course of treatment was independently increased by three factors: DAS28 before the second course, DAS28 at trial week 20, and Health Assessment Questionnaire at week 16.

Every 1 point that DAS28 was allowed to worsen before the second course of rituximab resulted in a 0.32-point higher DAS28 after the second course, according to Dr. Mease, who is a rheumatologist in Seattle.

Equally significant in the model but with the opposite effect on DAS28 was the peripheral CD19+ B-cell count before the second course: A count of at least 80 u 103/mL before the second course resulted in a 0.47-point lower DAS28 after the second course.

“The take-home message from this analysis is that in order to achieve the best DAS with a repeat course of rituximab, the preferable time for re-treatment is when the patient is starting to have resurgent symptoms,” Dr. Mease commented in an interview.

“On average, patient response lasts 6 months and at that point clinicians should start monitoring more diligently, looking for signs of disease activity. If the patient waits until 8 months for re-treatment, the resulting DAS won't be as good,” Dr. Mease added.

REFLEX was supported by Genentech, Biogen, and Roche. Dr. Mease has previously disclosed receiving consulting fees from Genentech and Biogen.

Symptom resurgence usually occurs about 6 months after ending the first course. DR. MEASE

BARCELONA — Patients with rheumatoid arthritis who are undergoing repeat courses of treatment with rituximab should begin re-treatment promptly once symptoms begin to recur, Dr. Philip J. Mease said at the annual European Congress of Rheumatology.

This conclusion emerged from analysis of the open-label extension phase of the Randomized Evaluation of Long-Term Efficacy of Rituximab in Rheumatoid Arthritis (REFLEX) trial, a double-blind, placebo-controlled multicenter study in which 298 patient initially received the active drug treatment.

All patients had failed at least one tumor necrosis factor blocker prior to beginning treatment with the B-cell-depleting agent. Those randomized to active treatment received two doses of rituximab, 1,000 mg, 2 weeks apart, plus stable doses of methotrexate.

Patients who achieved a 20% or greater improvement in swollen and tender joint counts during the 24-week blinded phase of the study were eligible to enter the open-label phase; 168 did so and had adequate follow-up for analysis 24 weeks after the second course of rituximab.

The four components of the 28-joint disease activity score (DAS28)—swollen joint count, tender joint count, erythrocyte sedimentation rate, and patient's global assessment—were assessed before each course of rituximab treatment, and every 4–8 weeks thereafter.

Mean DAS28 was 6.89 before the first course of rituximab and 6.12 before the second course, Dr. Mease wrote in a poster. The second course was administered at a median time of 43 weeks after the first course.

A generalized linear mixed model fit to all visits after the second course was used to evaluate the effects of various variables on DAS28, including pretrial patient and disease characteristics, DAS28 and Health Assessment Questionnaire at various times, and peripheral CD19+ B cell count before courses.

According to the model, DAS28 after the second course of treatment was independently increased by three factors: DAS28 before the second course, DAS28 at trial week 20, and Health Assessment Questionnaire at week 16.

Every 1 point that DAS28 was allowed to worsen before the second course of rituximab resulted in a 0.32-point higher DAS28 after the second course, according to Dr. Mease, who is a rheumatologist in Seattle.

Equally significant in the model but with the opposite effect on DAS28 was the peripheral CD19+ B-cell count before the second course: A count of at least 80 u 103/mL before the second course resulted in a 0.47-point lower DAS28 after the second course.

“The take-home message from this analysis is that in order to achieve the best DAS with a repeat course of rituximab, the preferable time for re-treatment is when the patient is starting to have resurgent symptoms,” Dr. Mease commented in an interview.

“On average, patient response lasts 6 months and at that point clinicians should start monitoring more diligently, looking for signs of disease activity. If the patient waits until 8 months for re-treatment, the resulting DAS won't be as good,” Dr. Mease added.

REFLEX was supported by Genentech, Biogen, and Roche. Dr. Mease has previously disclosed receiving consulting fees from Genentech and Biogen.

Symptom resurgence usually occurs about 6 months after ending the first course. DR. MEASE