Association Between Baseline Anti-cyclic Citrullinated Peptide Antibodies and 6-Month Clinical Response Following Abatacept or TNF Inhibitor Treatment: A Real-World Analysis of Biologic-Experienced Patients with RA

Anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with poor prognosis in patients with rheumatoid arthritis (RA). Previous data from randomized controlled trials and clinical practice have shown anti-CCP-positive (+) patients had a better response to treatment with abatacept or tumor necrosis factor inhibitor (TNFi) treatment than those who were anti-CCP negative. This study assessed the association between baseline anti-CCP2 [a surrogate for anti-citrullinated protein antibody (ACPA)] concentration and 6-month treatment responses to abatacept or TNFi in patients with RA. This real-world analysis included biologic-experienced patients from CERTAIN (Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory CoNditions) who initiated abatacept or TNFi, had prior biologic disease-modifying drug exposure and baseline anti-CCP2 concentration/serostatus and serum samples (baseline and 6 months). Baseline demographics and disease characteristics were compared. Change from baseline at 6 months in Clinical Disease Activity Index (CDAI) score and patient-reported outcomes [PROs: pain, fatigue, patient global assessment (PtGA), modified Health Assessment Questionnaire (mHAQ) score], by baseline anti-CCP2 quartile and binary cut-off (> 10–250 and > 250 U/ml), were evaluated separately in the abatacept and TNFi groups using a linear regression model adjusted for age, sex, CDAI/PROs, comorbidity index, and methotrexate use. Included were 138 abatacept and 137 TNFi initiators who were anti-CCP2+. At baseline, there were significant differences between anti-CCP2 quartiles and mean CDAI, swollen joint count 28, C-reactive protein (CRP), Disease Activity Score 28 (CRP), rheumatoid factor (RF), mHAQ and physician global assessment among abatacept initiators, and in mean RF, mHAQ, and PtGA among TNFi initiators. Among abatacept (but not TNFi) initiators, CDAI numerically improved (p = 0.208) and PROs significantly improved (p < 0.05) with increasing baseline anti-CCP2. In patients treated with abatacept, not TNFi, higher anti-CCP2 concentrations at baseline were associated with numerically greater improvements in CDAI and significant improvements in PROs after 6 months. NCT01625650. Rheumatoid arthritis (RA) is an autoimmune disease – a disease that causes the immune system to attack an individual’s own body. A key feature of RA is the presence of proteins called autoantibodies in the blood. While antibodies help protect against external threats such as viruses, autoantibodies mistakenly target an individual’s own tissues and organs. One type of autoantibody often found in patients with RA is called anti-cyclic citrullinated peptide (anti-CCP). Studies have shown that patients with RA with anti-CCP antibodies may experience worse physical symptoms, function, disease activity, and outcomes than patients with RA without anti-CCP antibodies. Clinical trials suggest that some drugs may be more effective than others at managing symptoms of RA in patients who have anti-CCP in their blood. It is important to study this further to give doctors a sense of how patients respond to drug therapy in the ‘real world’, without clinical trial constraints. This study examined real-world patient data to see whether the presence of anti-CCP in patients’ blood impacted how their RA symptoms responded to treatment with two different drugs: abatacept or a tumor necrosis factor inhibitor (TNFi). This study found that patients with higher levels of anti-CCP at the start of the study, compared with patients with lower levels of anti-CCP, experienced less disease activity and greater improvement in physical function after 6 months of treatment with abatacept. The study found no relationship between anti-CCP and treatment response after 6 months of treatment with a TNFi.

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