Existing joint erosions increase the risk of joint space narrowing independently of clinical synovitis in patients with early rheumatoid arthritis

Abstract

Introduction: Clinical synovitis is often associated with damage to bone and cartilage. Previous data have suggested that joint erosions (JE) are more prevalent than joint space narrowing (JSN) and that the two processes are partly independent of each other. The objective of this study was to evaluate whether the presence of JE in an individual joint can lead to development of JSN and if existing JSN leads to new onset of JE, in the absence of synovitis.

Methods: The Prospective Multi-Centre Randomised, Double-Blind, Active Comparator-Controlled, Parallel-Groups Study Comparing the Fully Human Monoclonal Anti-TNFα Antibody Adalimumab Given Every Second Week With Methotrexate Given Weekly and the Combination of Adalimumab and Methotrexate Administered Over 2 Years in Patients With Early Rheumatoid Arthritis (PREMIER) enrolled early rheumatoid arthritis (RA) patients who were randomized to one of three treatments: methotrexate (MTX), adalimumab (ADA), or ADA + MTX. All evaluable joints with JE and JSN measures at 26 and 52 weeks and synovitis assessments from week 26 to 52 were included. Synovitis was assessed every 2-8 weeks by swollen joint counts between weeks 26 and 52. Radiographs were taken at week 26 and 52. Two readers, blinded to time and sequence, scored 14 bilateral joints individually for JE and JSN. Multivariate logistic modeling was used to characterize the dependence of JE/JSN onset at 52 weeks. Analyses were performed based on treatment arm and were also performed within individual joints.

Results: JE and swelling were independently and comparably associated with onset of JSN at week 52. Assessment by individual joints indicated that existing JE, independent of swelling, was significantly associated with JSN onset in higher proportions of metatarsophalangeal (MTP; 7/10) than proximal interphalangeal (PIP; 1/8) or metacarpophalangeal (MCP; 1/10) joints. Treatment with ADA + MTX prevents JE/JSN progression independently of its ability to suppress synovitis and limits JE/JSN onset and progression in joints with existing damage.

Conclusions: Existing JE predisposes individual joints to development of JSN independently of synovitis in the same joint. Weight-bearing MTP joints with JE may be at increased risk for JSN when compared with MCPs and PIPs.

Trial registration: Clinicaltrials.gov NCT00195663. Registered 13 September 2005.

Figure 1

Association between existing JE, clinical synovitis, and treatment, and JSN onset in joints overall. (A) Ever swelling from 26 through 52 weeks and joint erosion (JE) presence at week 26 were independent predictors of presence of joint space narrowing (JSN) at 52 weeks. (B) The effect of treatment on the development of JSN at 52 weeks in joints with similar characteristics. (C) The association between ever swelling from 26 through 52 weeks and presence of JE at week 26, and JSN presence at 52 weeks, by treatment group. MTX, methotrexate; ADA, adalimumab.

Figure 2

Association between existing JSN, clinical synovitis, and treatment, and JE onset in joints overall. (A) Ever swelling from 26 through 52 weeks and presence of joint space narrowing (JSN) at week 26 were independent predictors of presence of joint erosion (JE) at 52 weeks. (B) Effect of treatment on the development of JE at 52 weeks in joints with similar characteristics. (C) Association between ever swelling from 26 through 52 weeks and presence of JSN at week 26, and presence of JE at 52 weeks, by treatment group. MTX, methotrexate; ADA, adalimumab.

Figure 3

Association between existing JE, clinical synovitis, and JSN, and JSN and JE onset in individual joints. (A) Odds ratios (95% CI) for the influence of existing joint erosions (JE) to predict future onset of joint space narrowing (JSN) in individual joint assessments. (B) Odds ratios (95% CI) for the influence of joint swelling to predict future onset of JSN in individual joint assessments. (C) Odds ratios (95% CI) for the influence of existing JSN to predict future onset of JE in individual joint assessments. (D) Odds ratios (95% CI) for the influence of joint swelling to predict future onset of JE in individual joint assessments. MCP, metacarpophalangeal; L, left; R, right; PIP, proximal interphalangeal; MTP, metatarsophalangeal.