Skip to main content

Table 2 Biochemical markers in rheumatoid arthritis clinical trials: selected studies evaluating biochemical markers

From: Biochemical markers of ongoing joint damage in rheumatoid arthritis - current and future applications, limitations and opportunities

Reference N Design/study if named Therapy Markers evaluated Results/timeframe
[168] 47 Open, single arm Adalimumab MMP-1, -3; COMP Decrease at 2 years only
[55] 49 Open, single arm Inflixamab (32)/etanercept (17) COMP Decrease at 3 months
[169] 68 Open, single arm Inflixamab Osteocalcin Increase weeks 2 to 6
     P1NP Increase weeks 2 to 6
     BAP No change
     CTX-I No change
     ICTP Decrease week 6
[170] 102 Open, single arm Inflixamab Osteocalcin No change
     CTX-I Decrease weeks 14 to 42
     RANKL Decrease week 14
     OPG No change
[24] 144 Post hoc, substudy in DB RCT Inflixamab (two dose levels) versus MTX CTX-I No change
     Col2-3/4c No change
     MMP-3 Decrease week 2
[98] 139/138 24-week DB RCT, MTX versus two dose levelsa Tocilizumab Osteocalcin Increase high dose
     CTX-I Decrease both doses
     ICTP Decrease both doses
     PIIANP Decrease, dose-related
     HELIX-II Decrease, dose-related
     MMP-3 Decrease, dose-related
[171] 132/124 DMARD monotherapy Sulfasalazine, MTX, and adjunctive corticosteroids MMPs, TIMP-1 COMP, glu-gal-pyr CTX-II 2 years, AUC measurements; MMP-3 + CTX-II, AUC was 81% for predictive accuracy
[172] 155 DMARD monotherapy Sulfasalazine, MTX, and adjunctive corticosteroids CTX-I, CTX-II Normalization of CTX-II predicted RA intervention efficacy
[106] 48 1-year, open, single arm (with BMD)b Inflixamab P1NP No change weeks 6 and 52
     CTX-I Decrease week 6
     ICTP Decrease week 52
     CTX-II No change
[109] 66 1-year, open, single arm, with X-rays at baseline and week 52c Inflixamab CTX-II No change
     Glc-Gal-PYD No change
[110, 111] 145/157 1-year, open RCT/X-rays (SAMURAI) Tocilizumab (anti-IL-6R) Osteocalcin Increase
     NTX Decrease
     PIIANPd Decrease
     MMP-3d Decrease
  1. aChanges with anti-IL-6R evident within 4 to 16 weeks, and at week 24 for CTX-I. bStable bone mineral density at month 12. cPatients with progressive joint damage had higher baseline levels. dWith hsCRP, modest correlation with progression of joint damage. AUC, area under the curve; BAP, bone alkaline phosphatase; COMP, cartilage oligomeric protein; CTX-I, C-terminal telopeptide of collagen type I; CTX-II, C-terminal telopeptide of collagen type II; DB, double blinded; DMARD, disease-modifying antirheumatic drug; hsCRP, high-sensitive CRP; ICTP, type I collagen; MMP, matrix metalloproteinase; MTX, methotrexate; NTX, N-terminal telopeptide of collagen type I; OPG, osteoprotegerin; PIIANP, amino terminus propeptide of type II procollagen, splice variant A; PINP, amino terminus propeptide of type I procollagen; RA, rheumatoid arthritis; RANKL, receptor activator of NF-kB ligand; RCT, randomized controlled trial; TIMP, tissue inhibitor of metalloproteinases.