Long-term effects of infliximab on bone and cartilage turnover markers in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is associated with systemic bone loss, subchondral bone erosion and cartilage degradation under the control of pro-inflammatory cytokines, including tumour necrosis factor alpha (TNFalpha). Therefore, we tested the hypothesis that administration of infliximab, an anti-TNFalpha drug in the treatment of RA, would modulate systemic and local bone resorption and reduce cartilage degradation. METHODS: We performed a prospective study of a multicentric cohort of 48 women, mean (SD) age 54.2 (12.1) years old, with severe RA for 11.4 (7.8) years, who started infliximab after failure of other disease-modifying antirheumatic drugs. At baseline and 6, 22 and 54 weeks after initiating Infliximab therapy we measured the following biochemical markers: pro-collagen serum type I N-terminal propeptide (PINP), a marker of bone formation; serum C-terminal cross-linked telopeptide of type I collagen (CTX-I), a marker of cathepsin K-mediated bone collagen degradation believed to reflect systemic bone resorption; serum C-terminal cross-linked telopeptide of type I collagen (ICTP), an index of matrix metalloprotease (MMP) mediated type I collagen degradation reflecting preferential joint metabolism; and urinary CTX-II a biochemical markers of cartilage degradation. Total hip and lumbar spine bone mineral density (BMD) was assessed at baseline, and after 6 and 12 months by dual-energy x-ray absorptiometry (DXA). No patient received bisphosphonates while 77% were under oral glucocorticoids. RESULTS: BMD remained stable over 1 year. Serum CTX-I levels rapidly decreased by 19% and 28% at week 6 and week 22, respectively (analysis of variance (ANOVA) p = 0.032) values returning to pre-treatment level at week 54. By contrast, ICTP levels progressively declined with a maximal 25% decrease at week 54 (ANOVA p = 0.028). By contrast, PINP levels remained stable over time, which led to a 30 to 40% improvement in bone remodelling balance, as assessed by the ratios PINP/CTX and PINP/ICTP (p<0.05). There was no significant change of urinary CTX-II in the whole population, but a slight decrease (ANOVA p = 0.041) in those with pre-treatment levels above the upper limit of normal range. CONCLUSIONS: In summary, the improvement in the formation/resorption marker ratio suggests beneficial systemic and local bone effects of infliximab in patients with RA.

Continuation of treatment with infliximab in ankylosing spondylitis: 2-yr open follow-up.

OBJECTIVE: To evaluate the continuation and safety of treatment with infliximab in ankylosing spondylitis (AS) over a 2-yr period. METHODS: This study was an open, observational, 2-yr extension study of an open-label study of three induction infusions of infliximab in refractory AS. The fourth infusion was performed only in case of relapse. Thereafter, infliximab was to be administered as needed according to the rheumatologist's opinion; however, for some patients, infusions were performed systematically. RESULTS: None of the 50 recruited patients was lost to follow-up. Thirteen patients (26%) interrupted their treatment by infliximab: four for inefficacy, seven for adverse events, of which four were for allergic reactions to the infusion, and two for other reasons. For all of the 46 patients who had had three infusions judged efficacious and well tolerated, a fourth infusion was performed because of a flare of the disease, after a mean interval of 20.3+/-9.9 weeks (range 7.3-57.9). Over the 24 months, the mean interval between infusions was 11.6+/-9.0 weeks. This interval was longer when patients were treated only as needed (mean 14.3+/-12.1 weeks) than systematically (mean 9.8+/-5.7 weeks). Side-effects were similar to those noted in shorter-term studies; seven patients suffered serious adverse events. There were no deaths, no malignancies and no tuberculosis. CONCLUSION: This study confirms the long-term treatment continuation of infliximab in AS, and shows an acceptable safety profile. It appears that for some patients the disease can be controlled with long intervals between infusions; these findings warrant further studies.

Outcome of subacute low back pain: influence of patients' and rheumatologists' characteristics.

OBJECTIVES: To assess the outcome of subacute low back pain, to identify the characteristics of patients and physicians which were related to outcome and to evaluate the influence of rheumatologists' beliefs about back pain on their following the guidelines for physical and occupational activity. DESIGN: a longitudinal descriptive survey. SETTING: a secondary care practice in France. PARTICIPANTS: 266 rheumatologists; 440 patients with subacute low back pain. OUTCOME MEASURES: the main outcome measure was persistence of back pain 3 months after baseline evaluation. A self-administered questionnaire for physicians assessed attitudes and beliefs about back pain [Fear-Avoidance Beliefs Questionnaire (FABQ)], and one for patients assessed pain, perceived handicap and disability (Quebec Scale), anxiety and depression (Hospital Anxiety Depression Questionnaire), and beliefs about back pain (FABQ). RESULTS: Forty per cent of patients had persistent low back pain at 3 months; 5.5% of these had sciatica. A total of 10% of rheumatologists and 68% of patients at baseline had a high FABQ physical score (phys; >14). Determinants of outcomes were work-related back pain [odds ratio (OR) = 3.37; 95% confidence interval (CI) 1.08-5.17], anxiety (OR = 2.41; 95% CI 1.44-4.09), sex (female OR = 2.03; 95% CI 1.30-3.18) and patients' beliefs about back pain at work (OR = 1.02; 95% CI 1.00-1.05). Physicians with high FABQ physical scores were less likely to follow guidelines on prescribing rest and occupational activity for back pain. CONCLUSION: Back pain commonly persists 3 months later in patients with subacute low back pain. Patients and rheumatologists still have negative beliefs about back pain. Rheumatologists' beliefs influence their following guidelines on physical and occupational activities. National education programmes about low back pain are needed in France.

Body weight, body composition, and bone turnover changes in patients with spondyloarthropathy receiving anti-tumour necrosis factor {alpha} treatment.

OBJECTIVES: To determine the changes in body weight, body composition, and bone turnover in patients with spondyloarthropathy (SpA) treated with anti-tumour necrosis factor alpha (TNFalpha). PATIENTS AND METHODS: 19 patients with SpA (2 women, 17 men), aged 21-71 years, were studied in a 1 year prospective open study. 17 patients received infliximab: 3 or 5 mg/kg/infusion at weeks 0, 2, 6 and infusions in the case of a relapse (n = 14) or systematically (n = 3); 2 patients received etanercept (25 mg twice a week). Body weight, body composition (lean mass, fat mass), and bone mineral density (BMD; using dual energy x ray absorptiometry) were measured at baseline and at months 6 and 12. Serum insulin-like growth factor-I (IGF-I), bone markers (carboxy terminal telopeptide of collagen Iota (CTX) and procollagen type Iota N terminal propeptide (PINP)) were measured at baseline and months 3, 6, and 12. RESULTS: In 1 year there was a significant increase in body weight (mean (SD) 2.24 (3.1) kg, p = 0.0004), and in lean mass (1.4 (1.69) kg, p = 0.005), but no changes in fat mass. BMD increased at the spine (5.6%, p = 0.0005) and total femur (2.6%, p = 0.01). CTX decreased from the third month (-50%, p = 0.005) up to 1 year (-30%, p = 0.012), and a trend for an increase in PINP (10%, p = 0.06) and in IGF-I (15%, p = 0.04) was seen at month 3. CONCLUSION: These data confirm that treatment with anti-TNFalpha in SpA is associated with an increase of BMD, which results from a decrease of bone resorption. Increase in body weight and lean mass is observed in parallel with an increase in IGF-1.

Evaluation of the symptomatic and structural efficacy of a new hyaluronic acid compound, NRD101, in comparison with diacerein and placebo in a 1 year randomised controlled study in symptomatic knee osteoarthritis.

OBJECTIVE: To evaluate long term efficacy of three iterative courses of three weekly intra-articular (IA) injections of NRD101 in the treatment of symptomatic knee osteoarthritis (OA). PATIENTS AND METHODS: A 1 year prospective, multicentre, randomised, double blind, placebo controlled study of 301 patients aged >50 years with painful and radiological medial knee OA. Patients were randomly assigned into three groups receiving: (1) three courses of three IA injections of hyaluronic acid (HA) + oral placebo; (2) IA injections of saline solution + diacerein 100 mg/day; (3) IA injections of saline solution + oral placebo. Demographic data and symptomatic criteria-pain, Lequesne's index, patient's global assessment of disease activity, percentage of painful days-were obtained during the study; primary structural criterion was JSW. Efficacy criteria were changes in pain VAS, joint space narrowing (JSN), and percentage of progressors (JSN >0.5 mm). An intention to treat analysis was used for symptomatic variables, and completer analysis for structural variables. RESULTS: Baseline characteristics were similar between the three groups. Mean (SD) improvement in pain VAS was clinically relevant (-33.9 (27.3), n = 301), but with no difference between the groups (p = 0.96). JSW deteriorated (-0.09 (0.55) mm, n = 277, p = 0.01), but with no difference between the groups (p = 0.82). Percentages of progressors were 17.7, 18.9, and 20.3% (p = 0.90), in groups 1, 2, and 3, respectively. CONCLUSION: A weak but statistically significant structural deterioration occurred over 1 year, together with clinically relevant symptomatic improvement in patients receiving oral drug and iterative IA injections. Symptomatic and/or structural effects for both this new HA compound and diacerein were not demonstrated.