Twice-daily maraviroc was not noninferior to efavirenz at <50 copies/mL in the primary analysis. However, 15% of patients would have been ineligible for inclusion by a more sensitive screening assay. Their retrospective exclusion resulted in similar response rates in both arms Trial registration. ClinicalTrials.gov identifier: (NCT00098293) .

BackgroundCombining bronchodilators with different mechanisms of action may improve efficacy and reduce risk of side effects compared to increasing the dose of a single agent in chronic obstructive pulmonary disease (COPD). We investigated this by combining two long-acting bronchodilators: once-daily muscarinic antagonist tiotropium and once-daily β2-agonist olodaterol.MethodsTwo replicate, double-blind, randomized, 12-week studies (ANHELTO 1 [NCT01694771] and ANHELTO 2 [NCT01696058]) evaluated the efficacy and safety of olodaterol 5 μg once daily (via Respimat®) combined with tiotropium 18 μg once daily (via HandiHaler®) versus tiotropium 18 μg once daily (via HandiHaler®) combined with placebo (via Respimat®) in patients with moderate to severe COPD. Primary efficacy end points were area under the curve from 0–3 hours of forced expiratory volume in 1 second (FEV1 AUC0–3) and trough FEV1 after 12 weeks (for the individual trials). A key secondary end point was health status by St George’s Respiratory Questionnaire (SGRQ) total score (combined data set).ResultsOlodaterol + tiotropium resulted in significant improvements over tiotropium + placebo in FEV1 AUC0–3 (treatment differences: 0.117 L [P<0.001], ANHELTO 1; 0.106 L [P<0.001], ANHELTO 2) and trough FEV1 (treatment differences: 0.062 L [P<0.001], ANHELTO 1; 0.040 L [P=0.0029], ANHELTO 2); these were supported by secondary end points. These effects translated to improvements in SGRQ total scores (treatment difference −1.85; P<0.0001). The tolerability profile of olodaterol + tiotropium was similar to tiotropium monotherapy.ConclusionThese studies demonstrated that olodaterol (Respimat®) and tiotropium (HandiHaler®) provided bronchodilatory effects above tiotropium alone in patients with COPD. In general, both treatments were well tolerated.

No abstract

Objective. To compare the clinical efficacy, effect on serum C-reactive protein (CRP), serum amyloid A (SAA), and plasma interleukin-6 (IL-6) levels, and safety of tenidap with a combination of hydroxychloroquineplus-piroxicam, and piroxicam alone, in the treatment of rheumatoid arthritis (RA) patients.Methods. A double-blind, randomized, multicenter study in which patients with active RA were treated with tenidap 120 mg/day, hydroxychloroquine 400 mglday and piroxicam 20 mglday, or piroxicam alone 20 mglday, for 24 weeks.Results. At weeks 12 and 24, tenidap produced greater improvements than piroxicam based on 5 primary efficacy parameters; this improvement showed statistical significance in 4 of the 5 measures at week 12, and in 3 of the 5 measures at week 24. Clinical improvements in the hydroxychloroquine-plus-piroxicamtreated patients were similar to those seen in patients treated with tenidap. Compared with piroxicam, tenidap was associated with significantly greater reductions in serum CRP concentrations at 4, 12, and 24 weeks, and significantly greater reductions in SAA concentrations at weeks 12 and 24. The decrease in SAA concentrations was also significantly greater at weeks 4 and 24 in the tenidap-treated group than in the hydroxychloroquine-plus-piroxicam-treated group. Significant reductions in plasma IL-6 levels were observed at weeks 4, 12, and 24 within the tenidap group, and at week 24 within the hydroxychloroquine-plus-piroxicam-treated group. The overall occurrence of side effects, including gastrointestinal side effects, was similar in all 3 treatment groups. A small proportion of tenidap-treated

Four independent studies have investigated and compared the effects of tenidap sodium, naproxen and placebo on CRP in patients with active RA. One of these studies also investigated the effects of tenidap and naproxen on serum amyloid A (SAA) concentrations and ESR. The duration of the four studies ranged between 2 weeks and 24 weeks, and depending on the study, tenidap sodium was administered orally in doses of 40-120 mg/day and naproxen in doses of 1000 mg/day. In all four studies serum CRP concentrations in tenidap-treated patients had decreased significantly from baseline at the time of final assessment. The decrease in CRP concentration in tenidap-treated patients was observed as early as 1 week after initiation of therapy and was sustained for up to 6 months, the last assessment timepoint. CRP concentrations in naproxen-treated and placebo patients were essentially unchanged. The decreases from baseline observed in tenidap-treated patients were significantly greater than the changes observed in naproxen-treated or placebo patients. After 24 weeks of tenidap treatment the decrease in CRP was paralleled by significant decreases in SAA concentration and ESR. The finding that tenidap sodium rapidly, consistently and significantly lowered CRP serum concentrations differentiates tenidap sodium from the NSAID, naproxen. This could possibly have important therapeutic implications given that other long-term investigations have shown that reducing serum CRP and SAA concentrations correlates with a reduction in radiographically-assessed disease progression.