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.

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.

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.

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.

Biomechanical effectiveness of a distraction-rotation knee brace in medial knee osteoarthritis: preliminary results.

BACKGROUND: Non-pharmacological therapies are recommended for the care of knee osteoarthritis patients. Unloader knee braces provide an interesting functional approach, which aims to modulate mechanical stress on the symptomatic joint compartment. We aimed to confirm the biomechanical effects and evaluate functional benefits of a new knee brace that combines a valgus effect with knee and tibial external rotation during gait in medial osteoarthritis patients. METHODS: Twenty patients with unilateral symptomatic medial knee osteoarthritis were included and they performed two test sessions of 3D gait analysis with and without the brace at the initial evaluation (W0) and after 5weeks (W5) of wearing the brace. VAS-pain, satisfaction scores, WOMAC scores, spatio-temporal gait parameters (gait speed, stride length, stance and double stance phases, step width), and biomechanical data of the ipsilateral lower limb (hip, knee, ankle and foot progression angles) were recorded at each session. RESULTS: VAS-pain and WOMAC significantly decreased at W5. Walking speed was not significantly modified by knee bracing at W0, but increased significantly at W5. Knee adduction moments and foot progression angles significantly decreased in the terminal stance and push off, respectively, with bracing at W0 and W5. Lower-limb joint angles, moments and powers were significantly modified by wearing the brace at W0 and W5. CONCLUSION: This new knee brace with distraction-rotation effects significantly alters knee adduction moments and foot progression angles during gait, which might lead to significant functional gait improvements and have carry-over effects on pain at the short term in osteoarthritis patients (<2 months). LEVEL OF EVIDENCE: level IV.