OBJECTIVES:
This prospective study aimed to use serological biomarkers for evaluation of, connective tissue turnover, in a population of 149 Japanese patients with rheumatoid arthritis (RA). It was aimed to investigate how the connective tissue was affected by treatment at follow-up after 1 year (+/- 6 weeks) with either methotrexate (n=23) alone, or in combination with: adalimumab (n=49), tofacitinib (n=27) or tocilizumab (n=50).

METHODS:
Clinical characteristics were collected and connective tissue turnover, was evaluated by 4 serological biomarkers: C1M and C3M reflect degradation of types I and III collagen in interstitial tissue; C4M, reflecting degraded type IV collagen of the basement membranes; and CRPM, a marker of degraded C-reactive protein. Evaluated biomarker levels were measured at baseline and at follow-up. Levels were compared to the reference levels of healthy individuals.

RESULTS:
The four evaluated biomarkers were all elevated at baseline in patients with RA compared to healthy individuals. The biomarkers were higher in RA patients compared to healthy individuals at baseline and they were all significantly correlated with disease activity score of 28 joint (DAS28) (p<0.0001). The biomarker levels were all significantly decreased in all four patient groups at follow-up in all of the four treatment groups.

CONCLUSIONS:
Rheumatoid joint inflammation elicits enhanced turnover of major collagen constituents of the synovial membrane and this abnormal pathway may be implicated in erosive progression. Evaluations of the applied biomarkers: C1M, C3M, C4M and CRPM, indicate that the pathologically enhanced tissue turnover was attenuated, by all of the four studied treatments.