Table 1.
Summary of the main studies investigating immune biomarkers as predictors of treatment response.
| Biomarker | Drug | Ethnicity | Concurrent DMARDs | Response Criteria | Predictor of Response | N Cases | Reference |
|---|---|---|---|---|---|---|---|
| Seropositive status | Infliximab | Caucasian | 100% | DAS28 ≥ 1.2 | Low ACPA titre predictive of response (PPV 0.95) | 30 | [23] |
| Caucasian | 73% | EULAR | Low RF/ACPA titre | 1195 | [24] | ||
| Infliximab | Asian | 100% | ΔCRP | Low RF titre | 62 | [25] | |
| Caucasian | 100% | EULAR | ACPA not associated with response | 42 | [26] | ||
| Caucasian | 100% | DAS28 | ACPA not associated with response | 31 | [27] | ||
| Mixed | n/a | DAS28 ACR20 EULAR |
Meta-analysis found no association between seropositive status and anti-TNF response | 5561 | [28] | ||
| Adalimumab | Caucasian | 100% | EULAR DAS28 ACR20 |
ACPA+ | 245 | [29] | |
| Infliximab | Asian | 100% | DAS28 | High RF/ACPA titre | 307 | [30] | |
| Caucasian | n/a | CDAI | No association | 1715 | [31] | ||
| Abatacept | Caucasian | 64.8% | EULAR | ACPA+ (OR 1.9; 1.2–2.9) | 558 | [32] | |
| Caucasian | 100% | EULAR DAS28 ACR20 |
High ACPA titre | 252 | [29] | ||
| Caucasian | n/a | Higher continuation of abatacept in seropositive cohorts | 1357 | [33] | |||
| Caucasian | n/a | CDAI | ACPA+ | 566 | [31] | ||
| Caucasian | 75% | Retention rate | Double RF+/ACPA+ | 2350 | [34] | ||
| Rituximab | Mixed | n/a | ACR20 EULAR |
Meta-analysis found RF+ associated with treatment response | 2103 | [35] | |
| Caucasian | n/a | DAS28 | Meta-analysis showing seropositive patients respond better to rituximab than seronegative patients | 2177 | [36] | ||
| Caucasian | 74.6% | EULAR DAS28 |
High ACPA titre | 114 | [37] | ||
| Tocilizumab | Mixed | n/a | ACR20 EULAR |
Meta-analysis found RF+ associated with treatment response | [35] | ||
| IL-6 | Etanercept | Asian | n/a | n/a | Increased IL-6 (with low survivin) associated with response (OR 19.7, CI 4.1–94.8) | 73 | [38] |
| Tocilizumab | Caucasian | 48.6% | EULAR | Increased IL-6 (with low IL-6R) associated with response | 63 | [39] | |
| IL-33 | Rituximab | Caucasian | 100% | EULAR | High IL-33 (and ACPA+) associated with response (OR 29.61, CI 1.3–674.8) | 74 | [40] |
| CXCL13 | Anti-TNFs | Caucasian | 100% | EULAR | High CXCL13 (and high CXCL10) associated with response (AUC 0.83) | 29 | [41] |
| Tocilizumab | Caucasian | 0% | ACR | High CXCL13 (with low sICAM1) (AUC 0.65) | 198 | [42] | |
| CCL19 | Rituximab | Caucasian | 100% | EULAR | High CCL19 associated with response (OR 1.43, CI 1.08–1.90) | 208 | [43] |
| B cells | Anti-TNFs | Caucasian | 69% | EULAR | High CD27+ B cells associated with response (RR 4.9, CI 1.3–18.6) | 21 | [44] |
| Abatacept | Caucasian | 51.2% | EULAR | High CD27+ and/or CD38+ B cells associated with response | 43 | [45] | |
| Rituximab | Caucasian | 100% | EULAR | High CD27− B cells are associated with response | 154 | [46] | |
| CD8+ T cells | Etanercept | Caucasian | n/a | EULAR | High apoptotic epitope-specific CD8+ T cells associated with response (AUC 0.82) | 16 | [47] |
| Abatacept | Caucasian | n/a | DAS28 | Low CD28− CD8+ T cells is associated with response | 32 | [48] | |
| NK cells | Tocilizumab | Caucasian | 60% | DAS28 | Low CD56brightCD16− NK cells associated with response | 20 | [49] |
| Type I interferon signature | Anti-TNF | Hispanic | 71–100% | EULAR | High type I IFN activity associated with response (OR 1.36, CI 1.05–3.29) | 35 | [50] |
| Rituximab | Caucasian | 55% | EULAR | High type I IFN signature negatively associated with response | 20 | [51] | |
| Caucasian | 77% | DAS28 | High type I IFN signature negatively associated with response (AUC 0.87) | 26 | [52] |
Table 1 outlines the main studies investigating immune biomarkers predicting treatment response in RA. Immune signatures are listed alongside the biologic drug studied, the ethnicity of the patient group, the percentage of the cohort taking concurrent disease-modifying anti-rheumatic drugs (DMARDs), the outcome measure used, the main findings, and the sample size. ACPA: Anti-citrullinated peptide antibody. ACR: American College of Rheumatology [53]. AUC: Area under the curve. CDAI: Clinical disease activity index. CI: Confidence interval. DAS28: Disease activity score in 28 joints [54]. EULAR: European League Against Rheumatism [55]. OR: Odds ratio. PPV: Positive predictive value. RF: Rheumatoid factor.