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Table 1 Summary of proteomic studies investigating response to biologic therapy

From: Right drug, right patient, right time: aspiration or future promise for biologics in rheumatoid arthritis?

Biomarker Sample size Treatment Main results Reference
24 autoantibodies and cytokinesa 3 independent cohorts, n = 93 ETN PPV 58–72%
NPV 63–78%
Hueber et al. [150]
7 proteins including acute phase reactants, proteins of the complement systemb 2 independent cohorts, n = 22/16 ETN AUC R/NR 0.86–1.0
PROS and CO7: sens 88.9%, spec 100%
Obry et al. [151]
12 cytokines and chemokinesc n = 33 ETN MCP1, EGF: good response
CRP + EGF: good response (AUC 0.844, sens 87.5%, spec 75%)
Fabre et al. [80]
14 proteins enriched in apolipoproteins, components of the complement system and acute phase reactantsd n = 8 IFX NR/R ratio 1.336–5.459
AUC 0.875–1.0
Ortea et al. [152]
6 proteins signalled, 2 identified: apolipoprotein A and platelet factor 4 n = 60 IFX AUC for all proteins 0.761–0.846
Combination: sens 97.1%, spec 97.5%
Apo-A: good response, PF4: non-response
Trocmé et al. [153]
12 biomarkers assembled into one multi-biomarker disease activity (MBDA) score n = 144 IFX vs triple txf Rapid radiographic progression lower with IFX if high MBDA Hambardzumyan et al. [154]
9 proteins differentiated responsee n = 8 ADA NR/R 1.42–2.18/0.42–0.73.
Independence to IFX results
Ortea et al. [155]
12 cytokines and chemokinesc n = 46 RTX Baseline cytokines profiles not related to response Fabre et al. [124]
  1. Original table summarising proteomic studies available to date that aimed to investigate response to biologic therapy in rheumatoid arthritis
  2. ADA adalimumab, AUC area under the curve, ETN etanercept, IFX infliximab, NPV negative predictive value, NR non-responder, PPV positive predictive value, R responder, sens sensitivity, spec specificity, RTX rituximab, tx therapy
  3. aGM-CSF, interleukin (IL)-6, fibromodulin, clusterin, ApoE, H2B/e, clusterin, HSP58, IL-1α, COMP, acetyl-calpastatin, biglycan, osteoglycin, serine protease-11, IL-1β, eotaxin, IP-10, FGF-2, MCP-1, IL-12p70, fibrinogen, FibA, IL-12p40, IL-15
  4. bCeruloplasmin, complement component C7 (CO7), inter-alpha-trypsin inhibitor heavy chain 1, plasminogen, vitamin K-dependent protein S (PROS), protein S100A9, zinc-alpha2-glycoprotein
  5. cIL-6, TNF-α, IL-1α, IL-1β, IL-2, IL-8, IFN-γ, IL-4, IL-10, monocyte chemoattractant protein (MCP)-1, epidermal growth factor (EGF), vascular endothelium growth factor
  6. dVitamin D-binding protein splicing variant GC-006, ceruloplasmin, apolipoprotein B-100, inter-alpha-trypsin inhibitor heavy chain H2, thrombospondin-1, complement C4-B alpha chain, inter-alpha-trypsin inhibitor heavy chain H1, gelsolin, apolipoprotein A-II, fibronectin isoform 7, complement factor H-related protein 4, apolipoprotein M, adipocyte plasma membrane-associated protein, mannan-binding lectin serine protease 2
  7. eTropomyosin alpha-4 chain, Transgelin-2, Cofilin-1, Hemopexin, complement C3, SH3 domain-binding glutamic acid-rich-like 3, transcription factor-like 5 protein, target of Nesh-SH3, Isoform 2 of Tropomyosin alpha-3 chain
  8. fTriple disease-modifying anti-rheumatic therapy: methotrexate, hydroxychloroquine, sulfasalazine