Seropositivity Predicts Good Response to Rituximab in RA

CHICAGO – Patients with rheumatoid arthritis who are seropositive for rheumatoid factor and/or anti-citrullinated-protein antibody respond better to rituximab than do seronegative patients, according to an observational study of 3,266 patients from the CERERRA collaboration.

Patients who were seropositive for either biomarker achieved significantly greater reductions in DAS28 and more EULAR good responses at 6 months. Baseline anti-citrullinated-protein antibody (ACPA) positivity may be a better predictor of EULAR good response to rituximab therapy than rheumatoid factor positivity.

"The aim of the CERERRA collaboration is to try to answer some of the clinical questions about rituximab treatment that remain unclear today, and one of these things is to find prognostic factors of response," said principal investigator Dr. Katerina Chatzidionysiou of the Karolinska Institute in Stockholm. "We know from clinical trials and epidemiological studies that seropositivity is correlated with a good response to rituximab. And to examine this in real-life patients, in an observational cohort, was the purpose of this analysis."

The study was designed to assess 6-month response to the first rituximab course in rheumatoid arthritis (RA) according to rheumatoid factor and ACPA status. Data came from the 10 European registries of CERERRA, the European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis, Dr. Chatzidionysiou said at the annual meeting of the American College of Rheumatology.

Anonymous data sets of patients with RA who had started rituximab were pooled and analyzed. The chi-square test was used to compare categorical variables, and the t-test was used for continuous data. Predictors of response were identified by univariate and multivariate logistic regression analysis.

A majority of the 3,266 patients in the CERERRA cohort were rheumatoid factor positive and ACPA positive. Of 2,553 patients whose rheumatoid factor status was known, 2,041 (79.9%) were rheumatoid factor positive and 512 (20.1%) were rheumatoid factor negative.

Of 1,198 patients whose ACPA status was known, 877 (73.2%) were ACPA positive and 321 (26.8%) were ACPA negative.

The patients were well balanced for demographics and baseline disease characteristics (ACPA-positive 1.1 plus or minus 1.0 versus ACPA-negative 1.3 plus or minus 1.1, P = .006).

At 6 months, there were greater DAS28 reductions in the rheumatoid factor–positive and ACPA-positive cohorts. This led Dr. Chatzidionysiou to make three observations: that seropositive patients achieved significantly greater DAS28 improvements at 6 months; that the difference was more pronounced between ACPA-positive and ACPA-negative patients, compared to rheumatoid factor–positive and negative; and that rheumatoid factor–negative and ACPA-negative patients also achieved a significant improvement from baseline to 6 months, although moderate compared with seropositive patients.

As for EULAR responses at 6 months, the study showed a significantly higher percentage of good responders among ACPA-positive patients versus ACPA-negative (23.9% versus 14.9%, P = .009), but the difference was borderline significant between rheumatoid factor–positive and negative patients (21.5% versus 17.4%, P = .06).

In adjusted univariate analysis, "It was mainly the ACPA status, positive versus negative, which was significantly correlated with EULAR good response to therapy at 6 months with an OR of 2.03," said Dr. Chatzidionysiou (ACPA+ [vs.-]: coefficient 0.71, OR [95% CI] 2.03 [1.14-3.60], P = .02).

Multivariate logistic regression analysis found that ACPA-positive status remained predictive (odds ratio 1.8; 95% confidence interval, 1.1-3.3; P = .05), as did the lower number of prior biologics (OR 0.5; 95% CI, 0.3-0.8; P = .007).

"This was important to correct for the number of prior biologic DMARDs because we know from previous analyses that the lower number of prior TNF inhibitors is a significant predictor of good response," said Dr. Chatzidionysiou.

She said the study was limited in that it was observational and uncontrolled, in that there was a concern for missing data, and for the heterogeneity between countries.

This is an investigator led initiative, supported by Roche.

CHICAGO – Patients with rheumatoid arthritis who are seropositive for rheumatoid factor and/or anti-citrullinated-protein antibody respond better to rituximab than do seronegative patients, according to an observational study of 3,266 patients from the CERERRA collaboration.

Patients who were seropositive for either biomarker achieved significantly greater reductions in DAS28 and more EULAR good responses at 6 months. Baseline anti-citrullinated-protein antibody (ACPA) positivity may be a better predictor of EULAR good response to rituximab therapy than rheumatoid factor positivity.

"The aim of the CERERRA collaboration is to try to answer some of the clinical questions about rituximab treatment that remain unclear today, and one of these things is to find prognostic factors of response," said principal investigator Dr. Katerina Chatzidionysiou of the Karolinska Institute in Stockholm. "We know from clinical trials and epidemiological studies that seropositivity is correlated with a good response to rituximab. And to examine this in real-life patients, in an observational cohort, was the purpose of this analysis."

The study was designed to assess 6-month response to the first rituximab course in rheumatoid arthritis (RA) according to rheumatoid factor and ACPA status. Data came from the 10 European registries of CERERRA, the European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis, Dr. Chatzidionysiou said at the annual meeting of the American College of Rheumatology.

Anonymous data sets of patients with RA who had started rituximab were pooled and analyzed. The chi-square test was used to compare categorical variables, and the t-test was used for continuous data. Predictors of response were identified by univariate and multivariate logistic regression analysis.

A majority of the 3,266 patients in the CERERRA cohort were rheumatoid factor positive and ACPA positive. Of 2,553 patients whose rheumatoid factor status was known, 2,041 (79.9%) were rheumatoid factor positive and 512 (20.1%) were rheumatoid factor negative.

Of 1,198 patients whose ACPA status was known, 877 (73.2%) were ACPA positive and 321 (26.8%) were ACPA negative.

The patients were well balanced for demographics and baseline disease characteristics (ACPA-positive 1.1 plus or minus 1.0 versus ACPA-negative 1.3 plus or minus 1.1, P = .006).

At 6 months, there were greater DAS28 reductions in the rheumatoid factor–positive and ACPA-positive cohorts. This led Dr. Chatzidionysiou to make three observations: that seropositive patients achieved significantly greater DAS28 improvements at 6 months; that the difference was more pronounced between ACPA-positive and ACPA-negative patients, compared to rheumatoid factor–positive and negative; and that rheumatoid factor–negative and ACPA-negative patients also achieved a significant improvement from baseline to 6 months, although moderate compared with seropositive patients.

As for EULAR responses at 6 months, the study showed a significantly higher percentage of good responders among ACPA-positive patients versus ACPA-negative (23.9% versus 14.9%, P = .009), but the difference was borderline significant between rheumatoid factor–positive and negative patients (21.5% versus 17.4%, P = .06).

In adjusted univariate analysis, "It was mainly the ACPA status, positive versus negative, which was significantly correlated with EULAR good response to therapy at 6 months with an OR of 2.03," said Dr. Chatzidionysiou (ACPA+ [vs.-]: coefficient 0.71, OR [95% CI] 2.03 [1.14-3.60], P = .02).

Multivariate logistic regression analysis found that ACPA-positive status remained predictive (odds ratio 1.8; 95% confidence interval, 1.1-3.3; P = .05), as did the lower number of prior biologics (OR 0.5; 95% CI, 0.3-0.8; P = .007).

"This was important to correct for the number of prior biologic DMARDs because we know from previous analyses that the lower number of prior TNF inhibitors is a significant predictor of good response," said Dr. Chatzidionysiou.

She said the study was limited in that it was observational and uncontrolled, in that there was a concern for missing data, and for the heterogeneity between countries.

This is an investigator led initiative, supported by Roche.

CHICAGO – Patients with rheumatoid arthritis who are seropositive for rheumatoid factor and/or anti-citrullinated-protein antibody respond better to rituximab than do seronegative patients, according to an observational study of 3,266 patients from the CERERRA collaboration.

Patients who were seropositive for either biomarker achieved significantly greater reductions in DAS28 and more EULAR good responses at 6 months. Baseline anti-citrullinated-protein antibody (ACPA) positivity may be a better predictor of EULAR good response to rituximab therapy than rheumatoid factor positivity.

"The aim of the CERERRA collaboration is to try to answer some of the clinical questions about rituximab treatment that remain unclear today, and one of these things is to find prognostic factors of response," said principal investigator Dr. Katerina Chatzidionysiou of the Karolinska Institute in Stockholm. "We know from clinical trials and epidemiological studies that seropositivity is correlated with a good response to rituximab. And to examine this in real-life patients, in an observational cohort, was the purpose of this analysis."

The study was designed to assess 6-month response to the first rituximab course in rheumatoid arthritis (RA) according to rheumatoid factor and ACPA status. Data came from the 10 European registries of CERERRA, the European Collaborative Registries for the Evaluation of Rituximab in Rheumatoid Arthritis, Dr. Chatzidionysiou said at the annual meeting of the American College of Rheumatology.

Anonymous data sets of patients with RA who had started rituximab were pooled and analyzed. The chi-square test was used to compare categorical variables, and the t-test was used for continuous data. Predictors of response were identified by univariate and multivariate logistic regression analysis.

A majority of the 3,266 patients in the CERERRA cohort were rheumatoid factor positive and ACPA positive. Of 2,553 patients whose rheumatoid factor status was known, 2,041 (79.9%) were rheumatoid factor positive and 512 (20.1%) were rheumatoid factor negative.

Of 1,198 patients whose ACPA status was known, 877 (73.2%) were ACPA positive and 321 (26.8%) were ACPA negative.

The patients were well balanced for demographics and baseline disease characteristics (ACPA-positive 1.1 plus or minus 1.0 versus ACPA-negative 1.3 plus or minus 1.1, P = .006).

At 6 months, there were greater DAS28 reductions in the rheumatoid factor–positive and ACPA-positive cohorts. This led Dr. Chatzidionysiou to make three observations: that seropositive patients achieved significantly greater DAS28 improvements at 6 months; that the difference was more pronounced between ACPA-positive and ACPA-negative patients, compared to rheumatoid factor–positive and negative; and that rheumatoid factor–negative and ACPA-negative patients also achieved a significant improvement from baseline to 6 months, although moderate compared with seropositive patients.

As for EULAR responses at 6 months, the study showed a significantly higher percentage of good responders among ACPA-positive patients versus ACPA-negative (23.9% versus 14.9%, P = .009), but the difference was borderline significant between rheumatoid factor–positive and negative patients (21.5% versus 17.4%, P = .06).

In adjusted univariate analysis, "It was mainly the ACPA status, positive versus negative, which was significantly correlated with EULAR good response to therapy at 6 months with an OR of 2.03," said Dr. Chatzidionysiou (ACPA+ [vs.-]: coefficient 0.71, OR [95% CI] 2.03 [1.14-3.60], P = .02).

Multivariate logistic regression analysis found that ACPA-positive status remained predictive (odds ratio 1.8; 95% confidence interval, 1.1-3.3; P = .05), as did the lower number of prior biologics (OR 0.5; 95% CI, 0.3-0.8; P = .007).

"This was important to correct for the number of prior biologic DMARDs because we know from previous analyses that the lower number of prior TNF inhibitors is a significant predictor of good response," said Dr. Chatzidionysiou.

She said the study was limited in that it was observational and uncontrolled, in that there was a concern for missing data, and for the heterogeneity between countries.

This is an investigator led initiative, supported by Roche.