Anti‑citrullinated peptide antibodies and their value for predicting responses to biologic agents: a review


Rheumatol Int DOI 10.1007/s00296-016-3506-3

Emilio Martin‑Mola1,7 · Alejandro Balsa1 · Rosario García‑Vicuna2 · Juan Gómez‑Reino3 · Miguel Angel González‑Gay4 · Raimon Sanmartí5 · Estíbaliz Loza

Abstract Anti-citrullinated peptide antibodies (ACPAs) play an important pathogenic role both at the onset and during the disease course. These antibodies precede the clinical appearance of rheumatoid arthritis (RA) and are associated with a less favorable prognosis, both clinically and radiologically. The objective of this work was to conduct a comprehensive review of studies published through September 2015 of ACPAs’ role as a predictor of the therapeutic response to the biological agents in RA patients. The review also includes summary of the biology and detection of ACPAs as well as ACPAs in relation to joint disease and CV disease and the possible role of seroconversion. The reviews of studies examining TNF inhibitors and tocilizumab yielded negative results. In the case of rituximab, the data indicated a greater probability of clinical benefit in ACPA+ patients versus ACPA− patients, as has been previously described for rheumatoid factor. Nonetheless, the effect is discreet and heterogeneous. Another drug that may have greater effectiveness in ACPA+ patients is abatacept. Some studies have suggested that the drug is more efficient in ACPA+ patients and that those patients show greater drug retention. In a subanalysis of the AMPLE trial, patients with very high ACPA titers who were treated with abatacept had a statistically significant response compared to patients with lower titers. In summary, the available studies suggest that the presence of or high titers of ACPA may predict a better response to rituximab and/or abatacept. Evidence regarding TNFi and tocilizumab is lacking. However, there is a lack of studies with appropriate designs to demonstrate that some drugs are superior to others for ACPA+ patients.

Abatacept more effective in RA patients with high levels ACPA


Impact of baseline anti-cyclic citrullinated peptide-2 antibody concentration on efficacy outcomes following treatment with subcutaneous abatacept or adalimumab: 2-year results from the AMPLE trial

Sokolove J, et al. Ann Rheum Dis 2015;0:1–6. doi:10.1136

ABSTRACT Objectives To examine whether baseline anti-cyclic citrullinated peptide-2 (CCP2) antibody status and concentration correlated with clinical outcomes in patients treated with abatacept or adalimumab on background methotrexate (MTX) in the 2-year AMPLE (Abatacept versus adaliMumab comParison in bioLogicnaïvE rheumatoid arthritis subjects with background MTX) study. Methods In this exploratory analysis, anti-CCP2 antibody concentration was measured at baseline, and antibody-positive patients were divided into equal quartiles, Q1–Q4, representing increasing antibody concentrations. Clinical outcomes analysed by baseline anti-CCP2 status and quartile included change from baseline in disease activity and disability and remission rates. Results Baseline characteristics were generally comparable across quartiles and treatment groups. In both treatment groups, anti-CCP2 antibody-negative patients responded less well than antibody-positive patients. At year 2, improvements in disease activity and disability and remission rates were similar across Q1–Q3, but were numerically higher in Q4 in the abatacept group; in contrast, treatment effects were similar across all quartiles in the adalimumab group. Conclusions In AMPLE, baseline anti-CCP2 positivity was associated with a better response for abatacept and adalimumab. Patients with the highest baseline antiCCP2 antibody concentrations had better clinical response with abatacept than patients with lower concentrations, an association that was not observed with adalimumab.

Comparison of the efficacies of abatacept and tocilizumab in patients with rheumatoid arthritis by propensity score matching


Ann Rheum Dis doi:10.1136/annrheumdis-2015-20778 Satoshi KuboShingo NakayamadaKazuhisa NakanoShintaro HirataShunsuke FukuyoIppei MiyagawaKentaro HanamiKazuyoshi Saito,Yoshiya Tanaka


Objective To compare the clinical outcomes at 1 year after the treatment with either abatacept or tocilizumab in patients with rheumatoid arthritis in routine clinical practice.

Methods To overcome potential bias in allocation to treatment with abatacept or tocilizumab, a propensity score based on multiple baseline characteristics variables was calculated and 102 of 194 patients treated with abatacept and 102 of 273 patients treated with tocilizumab were statistically extracted. Clinical outcomes were assessed.

Results The baseline characteristics were statistically comparable. At week 52, 72%/69% of patients (abatacept/tocilizumab) were still receiving treatment. The Simplified Disease Activity Index (SDAI) decreased from 28.7/27.7 at baseline to 14.0/12.5 at week 52 with abatacept/tocilizumab, respectively. At week 52, the remission rates for abatacept/tocilizumab were 18%/20%, respectively. No statistical difference in clinical efficacy between abatacept and tocilizumab was seen. Moreover, a subanalysis showed that abatacept and tocilizumab had similar effectiveness with or without methotrexate. However, prognostic factors at baseline contributing to the Clinical Disease Activity Index at week 52 were different between the two groups by multiple regression analysis. A higher rheumatoid factor (RF) titre and lower SDAI at baseline were associated with lower SDAI at week 52 in patients treated with abatacept, whereas patients receiving tocilizumab with a lower Health Assessment Questionnaire Disability Index and who were biologics-naïve at baseline had a lower SDAI at week 52.

Conclusions We compared patients treated with abatacept or tocilizumab after statistical adjustment by propensity score matching. Clinical efficacies, including SDAI, were comparable in both treatment groups. However, the predictive factors were different: abatacept appears to benefit patients with higher RF titres, and early induction of tocilizumab is an important factor for good clinical efficacy.

Similar RA Outcomes with Abatacept & Tocilizumab


The Rheumatologist

August 17, 2015 • By Will Boggs, MD

NEW YORK (Reuters Health)—Clinical outcomes of rheumatoid arthritis (RA) are similar with abatacept and tocilizumab treatment, but the factors that predict efficacy differ for the two agents.

Abatacept targets T cells, whereas tocilizumab targets interleukin-6, and both are used in patients whose disease has proven refractory to methotrexate.

Dr. Tanaka’s team used a propensity score-matched analysis to compare clinical outcomes of abatacept and tocilizumab treatment of 102 patients in each group and sought to determine the predictive factors of the efficacy of each treatment.

Retention rates at 52 weeks were similar for abatacept (71.6%) and tocilizumab (68.6%). Discontinuation for inadequate effect was more common with abatacept (22.5%) than with tocilizumab (16.7%), according to the Aug. 5 online report in Annals of the Rheumatic Diseases.

Patients experienced similar improvements in Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire Disability Index (HAQ-DI), and Clinical Disease Activity Index (CDAI) with abatacept and tocilizumab treatment.

In contrast, the improvement in DAS28-ESR (the 28-joint count disease activity score-erythrocyte sedimentation rate) was greater with tocilizumab than with abatacept.

Lower baseline SDAI and higher baseline rheumatoid factor titer predicted better CDAI outcomes of abatacept treatment, whereas previous use of a biological agent and lower baseline HAQ-DI score predicted better tocilizumab outcomes.

“These factors should be considered when choosing one of these drugs,” Dr. Tanaka said. “Thus, this report may contribute (to) progress in ‘precision medicine’ in the field of RA.”