Multireader assessment as an alternative to reference assessment to improve the detection of radiographic progression in a large longitudinal cohort of rheumatoid arthritis (ESPOIR).

INTRODUCTION: Structural damage progression is a major outcome in rheumatoid arthritis (RA). Its evaluation and follow-up in trials should involve radiographic scoring by 1 or 2 readers (reference assessment), which is challenging in large longitudinal cohorts with multiple assessments. OBJECTIVES: To compare the reproducibility of multireader and reference assessment to improve the feasibility of detecting radiographic progression in a large cohort of patients with early arthritis (ESPOIR). METHODS: We used 3 sessions to train 12 rheumatologists in radiographic scoring by the van der Heijde-modified Sharp score (SHS). Multireader scoring was based on 10 trained-reader assessments, each reader scoring a random sample of 1/5 of all available radiographs (for double scoring for each X-ray set) for patients included in the ESPOIR cohort with complete radiographic data at M0 and M60. Reference scoring was performed by 2 experienced readers. Scoring was performed blindly to clinical data, with radiographs in chronological order. We compared multireader and reference assessments by intraclass correlation coefficients (ICCs) for SHS and significant radiographic progression (SRP). RESULTS: The intrareader and inter-reader reproducibility for trained assessors increased during the training sessions (ICC 0.79 to 0.94 and 0.76 to 0.92), respectively. For the 524 patients included, agreement between multireader and reference assessment of SHS progression between M0 and M60 and SRP assessment were almost perfect, ICC (0.88 (95% CI 0.82 to 0.93)) and (0.99 (95% CI 0.99 to 0.99)), respectively. CONCLUSIONS: Multireader assessment of radiographic structural damage progression is comparable to reference assessment and could be used to improve the feasibility of radiographic scoring in large longitudinal cohort with numerous X-ray evaluations.

Response to tocilizumab in rheumatoid arthritis is not influenced by the body mass index of the patient.

OBJECTIVE: To assess the relationship between the body mass index (BMI) and the efficacy of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA). METHODS: We conducted a retrospective study in 222 patients with RA followed by 5 centers. The European League Against Rheumatism response was evaluated at 6 months. Univariate and multivariate logistic regressions were performed. RESULTS: No significant association between the BMI and the response to TCZ at 6 months was found after adjustment for potential confounding factors (adjusted OR 0.45, 95% CI 0.16-1.24, p = 0.13 and OR 1.19, 95% CI 0.31-4.48, p = 0.78 for BMI 25-30 kg/m(2) and BMI > 30 kg/m(2), respectively, compared to BMI < 25 kg/m(2)). CONCLUSION: Response to TCZ in patients with RA is not influenced by the baseline BMI, in contrast to anti-tumor necrosis factor drugs.

Tocilizumab induces corticosteroid sparing in rheumatoid arthritis patients in clinical practice.

OBJECTIVE: . The aim of this study was to evaluate the impact of introducing tocilizumab (TCZ) as co-therapy with CS in patients with RA. METHODS: This study was an open, observational, retrospective multicentre study. RA patients treated with oral CS for >3 months who started treatment with TCZ between December 2009 and June 2011 in five centres were included. Variables included demographic data, disease history, co-treatments, disease activity and dose of CS at inclusion and at weeks 4, 8, 12 and 24. The evolution of disease activity and of the dose of CS (analysis of variance with repeated measures) were analysed, searching for factors correlated with changes in the dose of CS. RESULTS: Inclusion of 130 patients [women 80.8%, mean age 56.7 years (s.d. 14.0), RA duration 16.3 years (s.d. 10.4), mean baseline 28-joint DAS (DAS28) 5.1 (s.d. 1.4), mean baseline dose of CS 10.0 mg/day (s.d. 8.2) prednisone equivalent. Decreases in the mean daily dose of CS and in the DAS28 were observed during follow-up [respectively 6.5 mg (s.d. 4.8) at week 24 (P < 0.0001) and 3.0 mg (s.d. 1.4) at week 24 (P < 0.0001)]. The only variable that correlated with the decrease in the dose of CS was the initial dose of the drug (r = 0.82, P < 0.001). CONCLUSION: The introduction of TCZ led to rapid and long-lasting CS sparing that did not correlate with the reduction in disease activity. It is possible that in patients treated with high-dose CS, the main objective of the clinician is to reduce dosage of CS rather than RA activity.

Efficacy and safety of tocilizumab in elderly patients with rheumatoid arthritis.

OBJECTIVE: To assess the safety and efficacy of tocilizumab (TCZ) in elderly (≥65 years) rheumatoid arthritis (RA) patients treated in daily practice. METHODS: We conducted a retrospective study of TCZ use in RA patients in five French university hospitals between 2009 and 2012. We considered two age groups, under 65 years (<65) and over 65 years (≥65). TCZ efficacy was evaluated at 24 weeks by the European League Against Rheumatism (EULAR) response and remission score. We also evaluated drug maintenance and safety, relative to adverse events discontinuation. A multivariate cumulative logit model for ordinal categories was performed to assess the relationship between age class and EULAR response (none, moderate and good) adjusted on possible confounders. TCZ retention (drug survival) over time was estimated with the Kaplan-Meier method. Treatment retention curves were compared according to age group with the log-rank test. RESULTS: Among 222 RA patients treated with TCZ, 61 (27.5%) were≥65 years at the initiation of treatment. After 6 months, this elderly patient group less often reached remission (27.8% versus 45.6%; P=0.02) or good EULAR response (40.7% versus 61.0%; P<0.01) compared to the younger patient group (<65). Multivariate analysis adjusted on baseline C-reactive protein and disease duration confirmed that elderly patients were more likely to have a lower EULAR response (none vs moderate-good or none-moderate vs good) (OR: 3.63; 95% CI [1.86-7.06], P<0.001) compared to younger patients. Drug maintenance for TCZ and adverse events discontinuation rates were similar between the two age groups. CONCLUSION: In daily practice, TCZ seems to be well tolerated in RA patients but is less efficient in elderly patients. A broader field of analysis to include an international register will be required to confirm these results.

Could biomarkers of bone, cartilage or synovium turnover be used for relapse prediction in rheumatoid arthritis patients?

OBJECTIVE: The aim of this review is to clarify the usefulness of bone, cartilage, and synovial biomarker in the management of rheumatoid arthritis (RA) therapy in remission. SYNOVIAL BIOMARKERS: High MMP-3 levels are associated with joint progression in RA patients, but there is no data about their utility in clinical remission. IIINys and Glc-Gal-PYD seem to be more specific to synovium, but more studies are required. CARTILAGE BIOMARKERS: Unbalance between cartilage break-down biomarkers (urinary CTX II and COMP) and cartilage formation biomarker (PIIANP) was described. This unbalance is also associated with joint destruction and prognosis of destruction. No data are available on patients in remission. BONE BIOMARKERS: RA activity is correlated with an increase of bone resorption markers such as CTX I, PYD, and TRACP 5b and a decrease of bone formation markers such as OC and BALP. RA therapies seem to improve bone turnover in limiting bone resorption. There is no study about bone marker utility in remission. CONCLUSION: Biomarkers seem to correlate with RA activity and progression. They also could be used to manage RA therapies, but we need more data on RA remission to predict relapse.

Predictors of response and remission in a large cohort of rheumatoid arthritis patients treated with tocilizumab in clinical practice.

OBJECTIVE: The objective of this study was to identify predictors of response and remission to tocilizumab (TCZ) in RA patients seen in daily routine clinical practice. METHODS: The efficacy of TCZ was evaluated after 12 and 24 weeks of treatment by the European League Against Rheumatism (EULAR) response criteria. Regression analysis was performed to study the association between remission or EULAR response and the following characteristics: gender, age, current smokers, prior cardiovascular disease (CVD), 28-joint disease activity score (DAS28), CRP, RF or ACPA positivity, combination therapy with DMARDs and TCZ as the first biological therapy or after failure of at least one biological therapy. RESULTS: In total, 204 patients were included with a mean DAS28 score of 5.14. EULAR response and remission were obtained in 86.1% and 40% of patients, respectively, at week 24. In multiple regression analysis, a high baseline CRP level [odds ratio (OR) 4.454 (95% CI 1.446, 13.726)] was significantly associated with EULAR response at week 24 and, inversely, age >55 years [OR 0.285 (95% CI 0.086, 0.950)] and prior CVD [OR 0.305 (95% CI 0.113, 0.825)] were significantly associated with lower EULAR response at week 24. Older age was also associated with less remission at week 24 [OR 0.948 (95% CI 0.920, 0.978)]. No additional effectiveness was found when TCZ was used in combination with a DMARD or when patients were naive to biological agents. CONCLUSION: In daily practice we identified three predictors of a better response for TCZ therapy in RA: a younger age, a high baseline CRP level and no history of CVD.