Retreatment With High-Dose Rituximab Reduced DAS28 Levels

CHICAGO – In patients with rheumatoid arthritis, initial treatment with two 500-mg infusions of rituximab or two 1,000-mg infusions led to comparable clinical outcomes.

But when the next course was given, only the rituximab regimen of two doses of 1,000 mg each was associated with further DAS28 reductions. This was the finding of an observational cohort study of 2,873 patients from the CERERRA collaboration.

"We know that the approved dose of rituximab in rheumatoid arthritis is 1,000 mg x 2, but some data from clinical trials have suggested similar clinical efficacy with 500 mg x 2. The purpose of this analysis was to compare the efficacy of the two dosages given as first or second treatment course," said principal investigator Dr. Katerina Chatzidionysiou of the Karolinska Institute in Stockholm.

Data for this study were collected from the 10 European registries of CERERRA (European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis). The data contained demographic, efficacy, and treatment information for patients who had started a course of rituximab. Efficacy of treatment and retreatment was assessed at 6 months for DAS28 reductions and EULAR responses, Dr. Chatzidionysiou said at the annual meeting of the American College of Rheumatology.

From a total of 3,266 patients, data on rituximab dosing were available for 2,873 (88%), of whom 2,625 (91.4%) received a regimen of two doses of 1,000 mg each and 248 (8.6%) received two doses of 500 mg each.

"Only the high dose, 1,000 mg, leads to significant improvements after retreatment."

There were significant differences between the groups in demographic and disease characteristics, said Dr. Chatzidionysiou. Patients treated with the lower dose were significantly older (55.2 plus or minus 15.8 years in the 500-mg group vs. 52.6 plus or minus 12.6 years in the 1,000-mg group, P = .002), had a longer duration of disease (13.6 plus or minus 11.9 years vs. 10.9 plus or minus 8.2 years, respectively, P less than .0001), and had used a lower number of prior biologics (0.7 vs. 1.0, P less than .0001). Patients in the lower-dose group were also more likely than those in the higher-dose group to have been treated with concomitant corticosteroids (65.7% vs. 59.3%, P = .03), and less likely to have been treated with concomitant disease-modifying antirheumatic drugs (72.6% vs. 83.1%, P less than .0001), with a majority using methotrexate (46.4% vs. 63.4%, P less than .0001). In the 500-mg group, 42% were identified as being anti–tumor necrosis factor (anti-TNF) agent naive, and the remaining 58% failed to respond to anti-TNF therapy. In the 1,000-mg group, 62.5% were anti-TNF naive and 37.5% failed to respond to anti-TNF therapy.

The two treatment groups started from different DAS28 baselines (5.7 plus or minus 1.3 in the 500-mg group vs. 5.9 plus or minus 1.3 in the 1,000-mg group, P = .02), and at 6 months, the DAS28 improvement was very similar (DAS28 score changed by 1.7 plus or minus 1.4 vs. 1.9 plus or minus 1.4, respectively, P = .5), said Dr. Chatzidionysiou.

No difference was observed in EULAR responses at 6 months, either, and no difference was noted according to whether the patients were anti-TNF naive or anti-TNF failures.

The study identified 622 patients who received a second cycle of rituximab: 579 were retreated with 1,000 mg and 26 with 500 mg. Seventeen patients who were retreated at different time points were eliminated from this count.

"We observed that when rituximab is given as a retreatment, the high dose leads to significantly better results at 6 months after therapy," said Dr. Chatzidionysiou.

"The DAS28 at 12 months was significantly lower in patients retreated with 1,000 mg," she said. EULAR responses and remission rates yielded similar results.

To compensate for the disparity in patient numbers between the two groups, a second, confirmatory analysis was performed using patients retreated only once during the first 12 months, at either 3, 6, or 9 months. This yielded 819 patients retreated with a high dose and 81 retreated with a lower dose.

"But again we came to a similar conclusion: Only the high dose, 1,000 mg, leads to significant improvements after retreatment," said Dr. Chatzidionysiou. Again, the EULAR responses and remission rates at 12 months were significantly higher with high-dose rituximab.

However, she noted, "it is difficult to interpret the results of the retreatment analysis because of the small number of patients and the differences between the two groups regarding baseline characteristics."

Dr. Chatzidionysiou disclosed being a consultant to Roche.

CHICAGO – In patients with rheumatoid arthritis, initial treatment with two 500-mg infusions of rituximab or two 1,000-mg infusions led to comparable clinical outcomes.

But when the next course was given, only the rituximab regimen of two doses of 1,000 mg each was associated with further DAS28 reductions. This was the finding of an observational cohort study of 2,873 patients from the CERERRA collaboration.

"We know that the approved dose of rituximab in rheumatoid arthritis is 1,000 mg x 2, but some data from clinical trials have suggested similar clinical efficacy with 500 mg x 2. The purpose of this analysis was to compare the efficacy of the two dosages given as first or second treatment course," said principal investigator Dr. Katerina Chatzidionysiou of the Karolinska Institute in Stockholm.

Data for this study were collected from the 10 European registries of CERERRA (European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis). The data contained demographic, efficacy, and treatment information for patients who had started a course of rituximab. Efficacy of treatment and retreatment was assessed at 6 months for DAS28 reductions and EULAR responses, Dr. Chatzidionysiou said at the annual meeting of the American College of Rheumatology.

From a total of 3,266 patients, data on rituximab dosing were available for 2,873 (88%), of whom 2,625 (91.4%) received a regimen of two doses of 1,000 mg each and 248 (8.6%) received two doses of 500 mg each.

"Only the high dose, 1,000 mg, leads to significant improvements after retreatment."

There were significant differences between the groups in demographic and disease characteristics, said Dr. Chatzidionysiou. Patients treated with the lower dose were significantly older (55.2 plus or minus 15.8 years in the 500-mg group vs. 52.6 plus or minus 12.6 years in the 1,000-mg group, P = .002), had a longer duration of disease (13.6 plus or minus 11.9 years vs. 10.9 plus or minus 8.2 years, respectively, P less than .0001), and had used a lower number of prior biologics (0.7 vs. 1.0, P less than .0001). Patients in the lower-dose group were also more likely than those in the higher-dose group to have been treated with concomitant corticosteroids (65.7% vs. 59.3%, P = .03), and less likely to have been treated with concomitant disease-modifying antirheumatic drugs (72.6% vs. 83.1%, P less than .0001), with a majority using methotrexate (46.4% vs. 63.4%, P less than .0001). In the 500-mg group, 42% were identified as being anti–tumor necrosis factor (anti-TNF) agent naive, and the remaining 58% failed to respond to anti-TNF therapy. In the 1,000-mg group, 62.5% were anti-TNF naive and 37.5% failed to respond to anti-TNF therapy.

The two treatment groups started from different DAS28 baselines (5.7 plus or minus 1.3 in the 500-mg group vs. 5.9 plus or minus 1.3 in the 1,000-mg group, P = .02), and at 6 months, the DAS28 improvement was very similar (DAS28 score changed by 1.7 plus or minus 1.4 vs. 1.9 plus or minus 1.4, respectively, P = .5), said Dr. Chatzidionysiou.

No difference was observed in EULAR responses at 6 months, either, and no difference was noted according to whether the patients were anti-TNF naive or anti-TNF failures.

The study identified 622 patients who received a second cycle of rituximab: 579 were retreated with 1,000 mg and 26 with 500 mg. Seventeen patients who were retreated at different time points were eliminated from this count.

"We observed that when rituximab is given as a retreatment, the high dose leads to significantly better results at 6 months after therapy," said Dr. Chatzidionysiou.

"The DAS28 at 12 months was significantly lower in patients retreated with 1,000 mg," she said. EULAR responses and remission rates yielded similar results.

To compensate for the disparity in patient numbers between the two groups, a second, confirmatory analysis was performed using patients retreated only once during the first 12 months, at either 3, 6, or 9 months. This yielded 819 patients retreated with a high dose and 81 retreated with a lower dose.

"But again we came to a similar conclusion: Only the high dose, 1,000 mg, leads to significant improvements after retreatment," said Dr. Chatzidionysiou. Again, the EULAR responses and remission rates at 12 months were significantly higher with high-dose rituximab.

However, she noted, "it is difficult to interpret the results of the retreatment analysis because of the small number of patients and the differences between the two groups regarding baseline characteristics."

Dr. Chatzidionysiou disclosed being a consultant to Roche.

CHICAGO – In patients with rheumatoid arthritis, initial treatment with two 500-mg infusions of rituximab or two 1,000-mg infusions led to comparable clinical outcomes.

But when the next course was given, only the rituximab regimen of two doses of 1,000 mg each was associated with further DAS28 reductions. This was the finding of an observational cohort study of 2,873 patients from the CERERRA collaboration.

"We know that the approved dose of rituximab in rheumatoid arthritis is 1,000 mg x 2, but some data from clinical trials have suggested similar clinical efficacy with 500 mg x 2. The purpose of this analysis was to compare the efficacy of the two dosages given as first or second treatment course," said principal investigator Dr. Katerina Chatzidionysiou of the Karolinska Institute in Stockholm.

Data for this study were collected from the 10 European registries of CERERRA (European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis). The data contained demographic, efficacy, and treatment information for patients who had started a course of rituximab. Efficacy of treatment and retreatment was assessed at 6 months for DAS28 reductions and EULAR responses, Dr. Chatzidionysiou said at the annual meeting of the American College of Rheumatology.

From a total of 3,266 patients, data on rituximab dosing were available for 2,873 (88%), of whom 2,625 (91.4%) received a regimen of two doses of 1,000 mg each and 248 (8.6%) received two doses of 500 mg each.

"Only the high dose, 1,000 mg, leads to significant improvements after retreatment."

There were significant differences between the groups in demographic and disease characteristics, said Dr. Chatzidionysiou. Patients treated with the lower dose were significantly older (55.2 plus or minus 15.8 years in the 500-mg group vs. 52.6 plus or minus 12.6 years in the 1,000-mg group, P = .002), had a longer duration of disease (13.6 plus or minus 11.9 years vs. 10.9 plus or minus 8.2 years, respectively, P less than .0001), and had used a lower number of prior biologics (0.7 vs. 1.0, P less than .0001). Patients in the lower-dose group were also more likely than those in the higher-dose group to have been treated with concomitant corticosteroids (65.7% vs. 59.3%, P = .03), and less likely to have been treated with concomitant disease-modifying antirheumatic drugs (72.6% vs. 83.1%, P less than .0001), with a majority using methotrexate (46.4% vs. 63.4%, P less than .0001). In the 500-mg group, 42% were identified as being anti–tumor necrosis factor (anti-TNF) agent naive, and the remaining 58% failed to respond to anti-TNF therapy. In the 1,000-mg group, 62.5% were anti-TNF naive and 37.5% failed to respond to anti-TNF therapy.

The two treatment groups started from different DAS28 baselines (5.7 plus or minus 1.3 in the 500-mg group vs. 5.9 plus or minus 1.3 in the 1,000-mg group, P = .02), and at 6 months, the DAS28 improvement was very similar (DAS28 score changed by 1.7 plus or minus 1.4 vs. 1.9 plus or minus 1.4, respectively, P = .5), said Dr. Chatzidionysiou.

No difference was observed in EULAR responses at 6 months, either, and no difference was noted according to whether the patients were anti-TNF naive or anti-TNF failures.

The study identified 622 patients who received a second cycle of rituximab: 579 were retreated with 1,000 mg and 26 with 500 mg. Seventeen patients who were retreated at different time points were eliminated from this count.

"We observed that when rituximab is given as a retreatment, the high dose leads to significantly better results at 6 months after therapy," said Dr. Chatzidionysiou.

"The DAS28 at 12 months was significantly lower in patients retreated with 1,000 mg," she said. EULAR responses and remission rates yielded similar results.

To compensate for the disparity in patient numbers between the two groups, a second, confirmatory analysis was performed using patients retreated only once during the first 12 months, at either 3, 6, or 9 months. This yielded 819 patients retreated with a high dose and 81 retreated with a lower dose.

"But again we came to a similar conclusion: Only the high dose, 1,000 mg, leads to significant improvements after retreatment," said Dr. Chatzidionysiou. Again, the EULAR responses and remission rates at 12 months were significantly higher with high-dose rituximab.

However, she noted, "it is difficult to interpret the results of the retreatment analysis because of the small number of patients and the differences between the two groups regarding baseline characteristics."

Dr. Chatzidionysiou disclosed being a consultant to Roche.