Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16†weeks of treatment: the CareRA trial.

OBJECTIVES: To compare the efficacy and safety of intensive combination strategies with glucocorticoids (GCs) in the first 16 weeks (W) of early rheumatoid arthritis (eRA) treatment, focusing on high-risk patients, in the Care in early RA trial. METHODS: 400 disease-modifying antirheumatic drugs (DMARD)-naive patients with eRA were recruited and stratified into high risk or low risk according to classical prognostic markers. High-risk patients (n=290) were randomised to 1/3 treatment strategies: combination therapy for early rheumatoid arthritis (COBRA) Classic (methotrexate (MTX)+ sulfasalazine+60 mg prednisone tapered to 7.5 mg daily from W7), COBRA Slim (MTX+30 mg prednisone tapered to 5 mg from W6) and COBRA Avant-Garde (MTX+leflunomide+30 mg prednisone tapered to 5 mg from W6). Treatment modifications to target low-disease activity were mandatory from W8, if desirable and feasible according to the rheumatologist. The primary outcome was remission (28 joint disease activity score calculated with C-reactive protein <2.6) at W16 (intention-to-treat analysis). Secondary endpoints were good European League Against Rheumatism response, clinically meaningful health assessment questionnaire (HAQ) response and HAQ equal to zero. Adverse events (AEs) were registered. RESULTS: Data from 98 Classic, 98 Slim and 94 Avant-Garde patients were analysed. At W16, remission was reached in 70.4% Classic, 73.6% Slim and 68.1% Avant-Garde patients (p=0.713). Likewise, no significant differences were shown in other secondary endpoints. However, therapy-related AEs were reported in 61.2% of Classic, in 46.9% of Slim and in 69.1% of Avant-Garde patients (p=0.006). CONCLUSIONS: For high-risk eRA, MTX associated with a moderate step-down dose of GCs was as effective in inducing remission at W16 as DMARD combination therapies with moderate or high step-down GC doses and it showed a more favourable short-term safety profile. EUDRACT NUMBER: 2008-007225-39.

A prospective randomised multicentre study comparing continuous and intermittent treatment with celecoxib in patients with osteoarthritis of the knee or hip.

OBJECTIVE: To compare the effects of continuous and intermittent celecoxib treatment in patients with knee or hip osteoarthritis in flare. METHODS: In this 24-week, prospective, randomised, double-blind, placebo-controlled study, patients were randomly assigned to receive continuous (n = 62) or intermittent (n = 61) treatment with celecoxib 200 mg once daily. The primary efficacy end point was the area under the curve (AUC) of the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total scores between baseline and week 24 divided by the time interval. Secondary end points included the percentage of days with intake of the flare drug, the AUC of the change in the WOMAC total scores, the mean change from baseline in the WOMAC scores, and the patient's and physician's global assessment of osteoarthritis. RESULTS: There were no significant differences between patients randomised to continuous or intermittent treatment in the primary end point or most of the secondary end points, although a consistent trend supporting continuous treatment was observed. The percentage of days with intake of the flare drug was significantly lower (p = 0.031) in the group receiving continuous versus intermittent celecoxib. Both treatment regimens were well tolerated. CONCLUSION: The results of this pilot study indicate a potential clinical difference between continuous and intermittent treatment with celecoxib, and may be useful in designing future trials. A larger trial on both efficacy and safety outcomes is required for conclusive evidence in favour of either continuous or intermittent treatment.

Etanercept 50 mg once weekly is as effective as 25 mg twice weekly in patients with ankylosing spondylitis.

OBJECTIVE: To compare the efficacy, pharmacokinetics and safety of etanercept 50 mg once weekly with 25 mg twice weekly and placebo in patients with ankylosing spondylitis. METHODS: A 12-week, double-blind, placebo-controlled study compared the effects of etanercept 50 mg once weekly, etanercept 25 mg twice weekly and placebo in 356 patients with active ankylosing spondylitis (3:3:1 randomisation, respectively). The primary end point was the proportion of patients achieving a response at week 12 based on the Assessment in Ankylosing Spondylitis Working Group criteria (ASAS 20). The pharmacokinetics of etanercept 50 mg once weekly and 25 mg twice weekly were analysed. RESULTS: Baseline characteristics and disease activity were similar among the three groups: etanercept 50 mg once weekly, etanercept 25 mg twice weekly and placebo. The percentage of patients discontinuing therapy was 9.0%, 9.3% and 13.7% for the three respective groups. ASAS 20 response at 12 weeks was achieved by 74.2% of patients with etanercept 50 mg once weekly and 71.3% of those with etanercept 25 mg twice weekly, both significantly higher than the percentage of patients taking placebo (37.3%, p<0.001). Percentages of patients with ASAS 5/6 response (70.3%, 72.0% and 27.5%, respectively; p<0.001) and those with ASAS 40 response (58.1%, 53.3% and 21.6%, respectively; p<0.001) followed a similar pattern. Significant improvement (p<0.05) was seen in measures of disease activity, back pain, morning stiffness and C reactive protein levels as early as 2 weeks. Serum etanercept exposure was similar between the etanercept groups. Incidence of treatment-emergent adverse events, including infections, was similar among all three groups, and no unexpected safety issues were identified. CONCLUSIONS: Patients with ankylosing spondylitis can expect a comparable significant improvement in clinical outcomes with similar safety when treated with etanercept 50 mg once weekly or with 25 mg twice weekly.

Determinants of gastro-protective drugs co-prescription during treatment with nonselective NSAIDs: a prospective survey of 2197 patients recruited in primary care.

OBJECTIVE: Our goal was to identify the magnitude of gastro-protective drugs (GPDs) co-prescription and the profile of patients who received GPD co-prescription, during nonsteroidal anti-inflammatory drugs (NSAIDs) treatment in a "real life setting" of primary care practice. METHODS: A pragmatic prospective 6-month survey of 2197 new takers of nonselective NSAIDs, selected and followed by general practitioners (GPs) on the bias of their usual standards of care. RESULTS: Forty-seven percent of our survey population used at least one GPD during the 6-month follow-up. No difference was identified between piroxicam, diclofenac, ibuprofen, meloxicam and nimesulid for the GPD co-prescription. Besides the presence of gastro-intestinal (GI) symptoms, previous use of GPD, previous occurrence of GI disorders and increase in age are the most prominent predictive factors of GPD use during NSAID treatment. When adjusted for other risk factors, co-prescription of GPD was significantly increased in patients aged 55 years and above (odds ratio (OR): 1.29, 95% confidence interval (CI): 1.01-1.64) with no further increase in the co-prescription in older subjects. CONCLUSION: Patients above 55 years with previous history of GI symptoms or GPD use are more likely to benefit from cytoprotective medications.

A naturalistic study of the determinants of health related quality of life improvement in osteoarthritic patients treated with non-specific non-steroidal anti-inflammatory drugs.

OBJECTIVES: To capture changes in the quality of life (QoL) occurring in patients with osteoarthritis (OA) during treatment with non-specific non-steroidal anti-inflammatory drugs (NSAIDs) and to identify factors that predict such changes. METHODS: A naturalistic, prospective follow up of 783 patients with OA in whom primary care physicians decided to start treatment with non-selective NSAIDs. Short Form-36 (SF-36) and the Western Ontario and McMaster Universities OA index (WOMAC) were assessed at baseline and after 3 months. Baseline results were compared with QoL values in 4800 subjects randomly selected from the general population. Multiple regression analysis was performed to identify determinants of QoL at baseline and measures influencing changes in SF-36 or WOMAC during follow up. RESULTS: All QoL dimensions were significantly (p<0.01) decreased in patients with OA compared with controls. Significant improvement (p<0.05) in four dimensions of the SF-36 (vitality, role emotional, role physical, bodily pain) and in all components of the WOMAC was seen between baseline and month 3. Older age, female sex, longer duration of OA, and a higher number of comorbidities were the major determinants of a poor QoL at baseline. Maximal benefit from non-specific NSAIDs was seen in patients with the most severe impairment in QoL and the shortest duration of OA. CONCLUSION: OA negatively impacts all dimensions of the QoL. Non-specific NSAIDs improve the QoL in patients with OA treated in a "real life setting". The profile of patients receiving maximal benefit from such treatment may be of interest for health providers, enabling them to decide who should preferentially be given cytoprotective treatments or coxibs.

[Involutional osteoporosis in women: therapeutic strategy. Recommendations of the Belgian Bone Club]. / L'ostéoporose involutive de la femme: stratégie thérapeutique. Un point de vue actualisé du Belgian Bone Club.

Osteoporosis is now considered as a major public health issue and a serious threat for the quality of life of elderly women. Several new compounds are currently marketed for the prevention and treatment of involutional osteoporosis in women. Therefore, it is important to offer to the practitioners pragmatic solutions to be used for the rational management of this disorder. This article is the result of a national consensus offering practical guidelines for the management of osteoporotic patients, based on the current published data.

A porcelain gallbladder affecting the assessment of bone mineral content.

Dual-photon absorptiometry is a reliable method for the assessment of bone mineral content (BMC). The presence of focal bone disease, degenerative joint disease, or aortic calcifications may complicate the evaluation of BMC and may lead to erroneous findings. The misleading effect of a porcelain gallbladder is described.

Intra-articular treatment of inflammatory arthritis: double-blind trial comparing bufexamac with methylprednisolone acetate.

A double-blind trial was carried out to weigh the effectiveness and tolerance of intraarticular injections of bufexamac (20 mg) against methylprednisolone (40 mg) in 40 patients with an acute bout of inflammatory arthritis. Leucocyte and polymorphonuclear counts and viscosity measurement of the synovial fluid were performed before and 14 days after injection, which showed methylprednisolone to be significantly superior to bufexamac in suppressing inflammation. In both groups a statistically significant improvement of pain on mobilisation and pain index was noted, but the number of clinical remissions was significantly higher in the methylprednisolone group. The blind investigator found a statistically significantly greater improvement with methylprednisolone than with bufexamac, and patients' opinion on effectiveness did not differ significantly. Important local or general side-effects were not observed. It was concluded that, although both drugs appeared to exert a considerable anti-inflammatory effect in inflammatory arthritis, methylprednisolone was more effective.

An European open multicentre trial with auranofin in rheumatoid arthritis.

In 8 European countries a multicentre trial was started in 672 patients with RA. The safety and efficacy of Auranofin (oral gold), was evaluated. There seems to be no difference in response to treatment between patients treated with Auranofin 3 mg twice daily or 6 mg once daily. From the fourth month of treatment there is a statistically difference in improvements for following parameters : activity index of Chalkins, articular index of Lansbury, ESR, pain, morning stiffness, grip strength, number of swollen joints and number of tender joints. These data suggest that Auranofin can be considered as a valuable disease modifying antirheumatic drug (DMARD) in RA and that early onset of therapy can be advised. In most cases the treatment is well tolerated.

Enumeration of T-lymphocytes and T-lymphocyte subsets in rheumatoid arthritis using monoclonal antibodies.

The number of T-lymphocytes and T-lymphocyte subsets was measured in peripheral blood of 51 patients with rheumatoid arthritis. T-lymphocytes were counted by E-rosette tests and by the immunogold staining method with OKT3.PAN monoclonal antibody. Helper and suppressor T-lymphocytes were determined by the immunogold staining method with OKT4.IND and OKT8.SUP monoclonal antibody. The relative and absolute numbers of T-lymphocytes and helper T-lymphocytes in peripheral blood of patients with RA did not differ significantly from those in the blood of healthy subjects. However, the relative and absolute numbers of suppressor T-cells were significantly lower in patients with RA than in healthy subjects. The decrease of suppressor T-cells in the blood of patients with RA dit not correlate with the activity of the disease nor the presence of the rheumatoid factor.

Enumeration of T lymphocytes subsets in autoimmune disease using monoclonal antibodies.

The numbers of T lymphocytes, B lymphocytes, helper and suppressor T lymphocytes were measured in peripheral blood of patients with autoimmune disease (rheumatoid arthritis, erythema nodosum, Sjögren's disease, Wegener's disease, idiopathic thrombocytopenia, pernicious anaemia and Hashimoto's disease). B lymphocytes were enumerated by direct immunofluorescence and T lymphocytes by E rosette tests and by indirect immunofluorescence with OKT3.PAN Helper and suppressor T lymphocytes were determined by indirect immunofluorescence with OKT4.IND and OKT8.SUP respectively. The numbers of T lymphocytes, B lymphocytes and helper T lymphocytes in patients with autoimmune disease were normal, but the numbers of suppressor T lymphocytes were significantly lower.