Studies of calprotectin as prognostic and predictive marker in RA.
| Study | n | Duration, Yrs | Main Findings | Adjustments | Outcome Measure |
|---|---|---|---|---|---|
| Structural damage | |||||
| Madland, et al29 | 56 | 5 | Calprotectin not independent disability and damage predictor (r = 0.17, p = 0.25). | NR | HAQ, Larsen score |
| Hammer, et al36 | 124 | 10 | Baseline calprotectin predicts clinical and erosive outcomes. ROC analysis: cutoff level 1.86 mg/l. Diagnostic sensitivity/specificity 69%/66%. Positive/negative LR 2.03/0.47. | Age, sex, disease duration, CRP, ESR, anti-CCP | Modified Sharp score, RAAD score |
| Therapeutic response | |||||
| Drynda, et al30 | 37 | 0.25 | Calprotectin levels decreased in response to etanercept (2 × 25 mg/week). Good responders (8.0–2.8 mg/l, p < 0.001, n = 11). Partial responders (19.8–11.1 mg/l, p < 0.05, n = 14). Nonresponders (17.4–12.3 mg/l, p > 0.05, n = 12). | None | DAS28 |
| De Rycke, et al31 | 20 | 0.1 | Calprotectin levels significantly decreased (635–345 µg/l, p < 0.001) in response to IFX (3 mg/kg at weeks 0, 2, and 6). | None | Serum calprotectin |
| Andrés Cerezo, et al37 | 43 | 0.25 | DMARD/GC therapy decreased calprotectin levels (5.99–2.49 mg/l, p < 0.0001). Multiple linear regression: decrease in calprotectin significant predictor for improvements in SJC (p = 0.001). | Age, sex, baseline calprotectin, CRP, ΔCRP | EULAR response criteria |
| Hammer, et al38 | 20 | 1 | Calprotectin levels decreased (2.02–1.08 mg/l, p = NS) with ADA (40 mg fortnightly). Correlation coefficients with the total BM and PD sum scores (r = 0.59 and r = 0.5, both p < 0.01). Linear regression analyses: calprotectin independently associated with both total sum US scores (p = 0.001–0.031). | Age, sex, disease duration, CRP, ESR, SAA | US (B-mode/Power Doppler) scores |
| García-Arias, et al39 | 20 | 0.5 | Calprotectin levels significantly decreased (p < 0.0001) after IFX treatment in responders (n = 10), but not in nonresponders (n = 10). Baseline calprotectin not a predictor of treatment response (baseline in responders vs nonresponders, 6.23 and 6.72 mg/l, p = 0.85). | None | EULAR response criteria |
| Choi, et al40 | 170 (86 ADA, 60 IFX, 24 RTX) | 0.3 | Significant decrease in calprotectin levels in responders to ADA, IFX (both p < 0.0001), and RTX (p < 0.0005). | DAS28, TJC68 | EULAR response criteria |
| At baseline, responders had significantly higher calprotectin levels compared with nonresponders (ADA 1.1 vs 0.73 mg/l, p = 0.010; IFX 2.7 vs 1.2 mg/l, p = 0.001; RTX 2.8 vs 1.1 mg/l, p < 0.001). | |||||
| High calprotectin baseline levels increased the odds of being a responder. ADA group (cutoff level 0.995 mg/l, OR 3.30, 95% CI 1.14–9.60, p = 0.028). IFX group (cutoff 2.027 mg/l, OR 9.75, 95% CI 1.93–49.33, p = 0.006). RTX group (cutoff level 1.665 mg/ml, OR 55, 95% CI 4.30–703.43, p = 0.002). | |||||
| ROC analyses: AUC for baseline calprotectin as predictor of response. ADA 0.688 (95% CI 0.571–0.804). IFX 0.791 (95% CI 0.575–0.907). RTX 0.984 (95% CI 0.945–1.000). | |||||
| Multivariate analyses: high baseline calprotectin level independent determinant of therapy response. ADA (OR 3.14, 95% CI 1.06–9.32, p = 0.040). IFX (OR 7.82, 95% CI 1.49–40.95, p = 0.006). RTX (OR 210.21, 95% CI 3.48–12,716.88, p = 0.002). |
RA: rheumatoid arthritis; NR: not reported; HAQ: Health Assessment Questionnaire; ROC: receiver-operating characteristic; LR: likelihood ratio; CRP: C-reactive protein; ESR: erythrocyte sedimentation rate; anti-CCP: anticyclic citrullinated peptide antibodies; RAAD: Rheumatoid Arthritis Articular Damage score; DAS28: 28-joint Disease Activity Score; IFX: infliximab; DMARD: disease-modifying antirheumatic drugs; GC: glucocorticoid; SJC: swollen joint count; ADA: adalimumab; BM: B-mode; PD: Power Doppler; US: ultrasonography; SAA: serum amyloid A; EULAR: European League Against Rheumatism; RTX: rituximab; AUC: area under the curve; TJC68: 68-joint tender joint count.