Table 6.

Validation studies of CTX-II as a prognostic biomarker for structural damage in RA

Study	Number of cases	Findings	Adjustments	Controls for treatment effect	Validated outcome measure used	Study design
Christgau et al. (2001)63	27	CTX-II levels were higher in patients with destructive arthritis	None	None	Not stated	Cross-sectional
Garnero et al. (2002)64	116	CTX-II was no better than CRP in predicting progression	Baseline modified Sharp score, CRP	Treatment group (etanercept or methotrexate)	Modified Sharp score	Longitudinal over 1 year
Garnero et al. (2002)56	110	Higher levels of CTX-II predicted more rapid progression, but only in those without damage at baseline	Baseline modified Sharp score, ESR, DAS28, seropositivity	Adjusted for treatment group (prednisolone with methotrexate and sulfasalazine, or sulfasalazine only)	Modified Sharp score	Longitudinal (median 4 years)
Landewé et al. (2004)57	110	Baseline CTX-II levels and early changes in CTX-II levels predicted change in damage	Baseline modified Sharp score, ESR, DAS28, seropositivity	Adjusted for treatment group (prednisolone with methotrexate and sulfasalazine, or sulfasalazine only)	Modified Sharp score	Longitudinal (median 4 years)
Forsblad d'Elia et al. (2004)59	88	Change in CTX-II levels over 24 months was not correlated with change in damage score	None	None	Larsen score	Longitudinal (2 years)
Young-Min et al. (2007)65	118	Higher baseline CTX-II and in-course CTX-II levels predicted more rapid progression	Joint count, physician global, DAS, ESR, CRP	Controlled for methotrexate use	Larsen score	Longitudinal (2 years)
Marotte et al. (2009)66	66	CTX-II levels were not associated with greater change in damage score	None	Controlled for Infliximab use and methotrexate use	Modified Sharp score	Longitudinal (1 year)
Hashimoto et al. (2009)67	145	Higher baseline CTX-II levels predicted more rapid progression	Baseline modified Sharp score, body mass index	None	Modified Sharp score	Longitudinal (1 year)
Christensen et al. (2009)68	45	CTX-II levels were not associated with more rapid progression	Age, gender, erosions at baseline, CRP, seropositivity	Controlled for methotrexate use	Larsen score	Longitudinal (1 year)
Christensen et al. (2010)69	133	Higher baseline CTX-II levels predicted more rapid progression	Age, gender, seropositivity, baseline modified Sharp score, DAS28	Controlled for methotrexate use, cyclosporin use, and corticosteroid use	Modified Sharp score	Longitudinal (4 years)
van Tuyl et al. (2010)62	73	Higher levels of CTX-II at 3 months (but not baseline) were associated with more rapid progression	Baseline modified Sharp score, ESR, seropositivity, RANKL:osteoprotegerin ratio	Adjusted for treatment group (prednisolone with methotrexate and sulfasalazine, or sulfasalazine only)	Modified Sharp score	Longitudinal (11 years)

Abbreviations: CTX-II, C-terminal crosslinked telopeptide of type II collagen; CRP, C-reactive protein; DAS, disease activity score; DAS28, DAS in 28 joints; ESR, erythrocyte sedimentation rate; RA, rheumatoid arthritis; RANKL, receptor activator of nuclear factor-κB ligand.