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

Karsdal, Morten A; Woodworth, Thasia; Henriksen, Kim; Maksymowych, Walter P; Genant, Harry; Vergnaud, Philippe; Christiansen, Claus; Schubert, Tanja; Qvist, Per; Schett, Georg; Platt, Adam; Bay-Jensen, Anne-Christine

doi:10.1186/ar3280

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 levels^a	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 52^c	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
				PIIANP^d	Decrease
				MMP-3^d	Decrease

^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.

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