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Objective <p>Anti-cyclic citrullinated peptide (anti-CCP) antibodies are established diagnostic markers for rheumatoid arthritis (RA), yet data on their prognostic implications in Middle Eastern populations remain limited. We aimed to evaluate clinical, functional, and radiographic differences between anti-CCP-seropositive and seronegative RA patients and to identify independent factors associated with disease severity.</p> Methods <p>This cross-sectional study included 200 RA patients fulfilling the 2010 ACR/EULAR criteria, stratified into anti-CCP-positive (<i>n</i> = 131, 65.5%) and anti-CCP-negative (<i>n</i> = 69, 34.5%) groups. Disease activity (DAS28-ESR), functional disability (HAQ-DI), radiographic damage (Larsen score), extra-articular manifestations, and laboratory parameters were assessed. Treatment data reflect the rheumatologist’s prescription at the time of enrolment; formal adherence was not assessed. Multivariate logistic and linear regression analyses were performed to identify independent factors associated with disease activity (DAS28 &gt; 5.1) and severe radiographic damage (Larsen ≥ 10). Post-hoc power analysis confirmed adequate statistical power (83%) for the primary DAS28-ESR comparison (Cohen’s d = 0.42).</p> Results <p>Anti-CCP-positive patients had significantly higher DAS28-ESR (5.18 ± 1.33 vs. 4.63 ± 1.27, <i>p</i> = 0.005; d = 0.42), HAQ-DI (0.93 ± 0.76 vs. 0.72 ± 0.66, <i>p</i> = 0.049; d = 0.29), and Larsen scores (median 6 [IQR 2–12] vs. 4 [IQR 1.5–6], <i>p</i> = 0.004; <i>r</i> = 0.22). High disease activity was more prevalent in seropositive patients (52.7% vs. 36.2%, <i>p</i> = 0.028). On multivariate analysis, anti-CCP positivity was independently associated with high disease activity (OR 2.14, 95% CI 1.12–4.09, <i>p</i> = 0.021) and severe radiographic damage (OR 2.47, 95% CI 1.18–5.17, <i>p</i> = 0.016). Double seropositivity (anti-CCP+/RF+) was associated with the most severe phenotype across all disease domains. ROC analysis yielded AUC values of 0.59 (95% CI 0.51–0.67) for high disease activity and 0.61 (95% CI 0.53–0.69) for severe radiographic damage.</p> Conclusions <p>Anti-CCP seropositivity was independently associated with a more severe RA phenotype in Egyptian patients. Combined serological profiling enhances risk stratification and should inform treatment intensification decisions within structured treat-to-target frameworks.</p>

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Serological Phenotyping of Rheumatoid Arthritis Based on Anti-Cyclic Citrullinated Peptide Antibody Status: Association with Disease Activity, Functional Disability, and Radiographic Damage in an Egyptian Cohort

  • 期刊论文

  • 发表日期：

    2026年6月29日

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  • Adel Ibrahim Azzam,
  • Hatem Galal Ibrahim,
  • Ahmed Shibl Ezz

摘要

Objective

Anti-cyclic citrullinated peptide (anti-CCP) antibodies are established diagnostic markers for rheumatoid arthritis (RA), yet data on their prognostic implications in Middle Eastern populations remain limited. We aimed to evaluate clinical, functional, and radiographic differences between anti-CCP-seropositive and seronegative RA patients and to identify independent factors associated with disease severity.

Methods

This cross-sectional study included 200 RA patients fulfilling the 2010 ACR/EULAR criteria, stratified into anti-CCP-positive (n = 131, 65.5%) and anti-CCP-negative (n = 69, 34.5%) groups. Disease activity (DAS28-ESR), functional disability (HAQ-DI), radiographic damage (Larsen score), extra-articular manifestations, and laboratory parameters were assessed. Treatment data reflect the rheumatologist’s prescription at the time of enrolment; formal adherence was not assessed. Multivariate logistic and linear regression analyses were performed to identify independent factors associated with disease activity (DAS28 > 5.1) and severe radiographic damage (Larsen ≥ 10). Post-hoc power analysis confirmed adequate statistical power (83%) for the primary DAS28-ESR comparison (Cohen’s d = 0.42).

Results

Anti-CCP-positive patients had significantly higher DAS28-ESR (5.18 ± 1.33 vs. 4.63 ± 1.27, p = 0.005; d = 0.42), HAQ-DI (0.93 ± 0.76 vs. 0.72 ± 0.66, p = 0.049; d = 0.29), and Larsen scores (median 6 [IQR 2–12] vs. 4 [IQR 1.5–6], p = 0.004; r = 0.22). High disease activity was more prevalent in seropositive patients (52.7% vs. 36.2%, p = 0.028). On multivariate analysis, anti-CCP positivity was independently associated with high disease activity (OR 2.14, 95% CI 1.12–4.09, p = 0.021) and severe radiographic damage (OR 2.47, 95% CI 1.18–5.17, p = 0.016). Double seropositivity (anti-CCP+/RF+) was associated with the most severe phenotype across all disease domains. ROC analysis yielded AUC values of 0.59 (95% CI 0.51–0.67) for high disease activity and 0.61 (95% CI 0.53–0.69) for severe radiographic damage.

Conclusions

Anti-CCP seropositivity was independently associated with a more severe RA phenotype in Egyptian patients. Combined serological profiling enhances risk stratification and should inform treatment intensification decisions within structured treat-to-target frameworks.