Towards the Lowest Efficacious Dose: Results From a Multicenter Noninferiority Randomized Open-Label Controlled Trial Assessing Tocilizumab or Abatacept Injection Spacing in Rheumatoid Arthritis in Remission.

OBJECTIVE: We assess the clinical and structural impact at two years of progressively spacing tocilizumab (TCZ) or abatacept (ABA) injections versus maintenance at full dose in patients with rheumatoid arthritis in sustained remission. METHODS: This multicenter open-label noninferiority (NI) randomized clinical trial included patients with established rheumatoid arthritis in sustained remission receiving ABA or TCZ at a stable dose. Patients were randomized to treatment maintenance (M) at full dose (M-arm) or progressive injection spacing (S) driven by the Disease Activity Score in 28 joints every 3 months up to biologics discontinuation (S-arm). The primary end point was the evolution of disease activity according to the Disease Activity Score in 44 joints during the 2-year follow-up analyzed per protocol with a linear mixed-effects model, evaluated by an NI test based on the one-sided 95% confidence interval (95% CI) of the slope difference (NI margin 0.25). Other end points were flare incidence and structural damage progression. RESULTS: Overall, 202 of the 233 patients included were considered for per protocol analysis (90 in S-arm and 112 in M-arm). At the end of follow-up, 16.2% of the patients in the S-arm could discontinue their biologic disease-modifying antirheumatic drug, 46.9% tapered the dose and 36.9% returned to a full dose. NI was not demonstrated for the primary outcome, with a slope difference of 0.10 (95% CI 0.10-0.31) between the two arms. NI was not demonstrated for flare incidence (difference 42.6%, 95% CI 30.0-55.1) or rate of structural damage progression at two years (difference 13.9%, 95% CI -6.7 to 34.4). CONCLUSION: The Towards the Lowest Efficacious Dose trial failed to demonstrate NI for the proposed ABA or TCZ tapering strategy.

Severe hypovitaminosis D correlates with increased inflammatory markers in HIV infected patients.

BACKGROUND: Even though it has been suggested that antiretroviral therapy has an impact on severe hypovitaminosis D (SHD) in HIV infected patients, it could be speculated that the different levels of residual inflammation on HAART (Highly Active Anti Retroviral Therapy) could contribute to SHD and aggravate bone catabolism in these patients. METHODS: A cross-sectional study was carried out in an unselected cohort of 263 HIV infected outpatients consulting during Spring 2010. Clinical examinations were performed and medical history, food habits, sun exposure and addictions were collected. Fasting blood samples were taken for immunological, virological, inflammation, endocrine and bone markers evaluations. RESULTS: Ninety-five (36%) patients had SHD. In univariate analysis, a significant and positive association was found between SHD and IL6 (p = 0.001), hsCRP (p = 0.04), increased serum C-Telopeptides X (CTX) (p = 0.005) and Parathyroid Hormon (PTH) (p < 0.0001) levels. In multivariate analysis, SHD deficiency correlated significantly with increased IL-6, high serum CTX levels, lower mean daily exposure to the sun, current or past smoking, hepatitis C, and functional status (falls), but not with the time spent on the current HAART (by specific drug or overall). CONCLUSIONS: SHD is frequent and correlates with inflammation in HIV infected patients. Since SHD is also associated with falls and increased bone catabolism, it may be of interest to take into account not only the type of antiretroviral therapy but also the residual inflammation on HAART in order to assess functional and bone risks. This finding also suggests that vitamin D supplementation may be beneficial in these HIV-infected patients.

Study of professional practices among rheumatologists in Burgundy: initial corticotherapy in polymyalgia rheumatica.

To study the initial dose of corticoids prescribed by rheumatologists in the Côte d'Or, a French department of Burgundy, in the treatment of polymyalgia rheumatica (PMR), the clinical and biological data of patients who consulted rheumatologists of the Côte d'Or between March 2006 and December 2008 for PMR were collected. The statistical analyses concerned the initially prescribed dose of prednisone: the median, mean, and standard deviation were calculated cumulatively and then for individual rheumatologists; the Mann-Whitney test was used to compare the mean initial doses prescribed with regard to (a) the main practice of the practitioner (private-practice or hospital rheumatologist), (b) the presence of clinical signs of severity, (c) severity of the inflammatory syndrome, and (d) the presence of clinical relapse with the decrease in corticoids. Ninety-nine patients were included (age = 72 ± 8.6 years, 59% women). The mean dose of prednisone prescribed was 27.4 ± 12.4 mg/day. Considerable inter- and intra-individual variabilities in the doses prescribed were noted. There was no significant difference concerning the dose prescribed according to the clinical severity or the type of practice. However, the dose was significantly higher (34.3 ± 14.7 vs. 25.5 ± 11.1 mg/day) in patients with a high sedimentation rate. Clinical relapse was not statistically linked to the initial dose of corticoids. This evaluation of professional practices among French rheumatologists shows that the initial dose of prednisone prescribed in PMR varies considerably and is higher than the dose currently recommended in the literature (15 mg/day).

Tolerability of opioids in patients with acute pain due to nonmalignant musculoskeletal disease. A hospital-based observational study.

OBJECTIVE: To evaluate the prevalence of adverse effects of opioids used to treat acute nonmalignant musculoskeletal pain. METHODS: Prospective, single-center, observational study in patients admitted to a rheumatology department for a nonmalignant painful musculoskeletal condition with onset within the last 3 months and a need for WHO Class III analgesics. The following side effects were recorded daily: nausea and vomiting, constipation, pruritus, urinary retention, drowsiness, confusion, and hallucinations. RESULTS: The 75 study patients (46 women and 29 men with a mean age of 56.4 years) were admitted for nerve root pain, osteoporotic vertebral fracture, inflammatory joint disease, or other disorders. First-line treatment was sustained-release morphine sulfate in a mean starting dosage of 55.2 mg/day. The dosage was increased if needed (mean maximum dosage, 78.3 mg/day). Mean treatment duration was 8.9 days. Adverse effects were recorded in 73.3% of patients but were usually minor, requiring no change in the treatment regimen. Eight patients experienced serious adverse effects (confusion in five and urinary retention in three) that resolved with no change in treatment in two patients, after dosage reduction in two patients and after substitution of fentanyl or hydromorphone hydrochloride in four patients. Treatment discontinuation was not associated with adverse effects. CONCLUSIONS: Morphine is often responsible for adverse effects in patients with acute nonmalignant musculoskeletal pain. These effects are usually moderate and very rarely require discontinuation of the drug.