Sustained efficacy of certolizumab pegol added to methotrexate in the treatment of rheumatoid arthritis: 2-year results from the RAPID 1 trial

Objective. To evaluate the safety and efficacy of 2-year administration of certolizumab pegol (CZP)?+?MTX in patients with active RA. Methods. Patients completing 52 weeks in the Rheumatoid Arthritis Prevention of Structural Damage (RAPID) 1 trial (52-week completers), or withdrawing at week 16 due to lack of ACR20 response were eligible for open-label treatment (CZP 400?mg every other week?+?MTX). After 2 years' treatment, HAQ-Disability Index response, ACR20/50/70 responses, DAS-28 and radiographic progression were assessed in 52-week completers. ACR20/50/70 and DAS-28 were also calculated for the intent-to-treat (ITT) population. Adverse events were assessed in patients who received one or more CZP doses during the study. Results. At week 100, 88.9% (n?=?216) of 52-week completers who originally received CZP 200?mg?+?MTX and open-label treatment remained in the study. In this group, ACR20/50/70 at week 100 were 68.2, 55.2 and 35.6%, respectively. HAQ-DI and DAS-28 improvements were sustained throughout the open-label extension (mean change -0.79 and -3.5 at week 100, respectively). A total of 46.7% (n?=?113) of CZP 200?mg?+?MTX 52-week completers achieved low disease activity by week 100. Inhibition of radiographic progression was maintained. Similar findings were observed in 52-week completers who originally received CZP 400?mg?+?MTX and in the ITT population. Rates of serious infection or malignancies did not increase over time and no new safety signals were observed. Conclusion. CZP?+?MTX provided sustained, 2-year inhibition of radiographic progression and sustained improvements in RA clinical signs and symptoms, with no new safety signals observed in patients who completed 2 years of treatment. Trial registration: clinicaltrials.gov, http://www.clinicaltrials.gov, NCT00175877.     

High-dose inhaled terbutaline increases muscle strength and enhances maximal sprint performance in trained men

Purpose

The purpose of the present study was to investigate the effect of high-dose inhaled terbutaline on muscle strength, maximal sprinting, and time-trial performance in trained men.

Methods

Nine non-asthmatic males with a \(\dot{V}O_{2max}\) of 58.9 ± 3.1 ml min^?1 kg^?1 (mean ± SEM) participated in a double-blinded randomized crossover study. After administration of inhaled terbutaline (30 × 0.5 mg) or placebo, subjects’ maximal voluntary isometric contraction (MVC) of m.quadriceps was measured. After MVC, subjects performed a 30-s Wingate test. Sixty minutes following the Wingate test, subjects exercised for 10 min at 80 % of \(\dot{V}O_{2max}\) and completed a 100-kcal time trial. Aerobic contribution was determined during the Wingate test by indirect calorimetry. Furthermore, plasma terbutaline, lactate, glucose, and K⁺ were measured.

Results

Inhalation of 15 mg terbutaline resulted in systemic concentrations of terbutaline of 23.6 ± 1.1 ng ml^?1 30 min after administration, and elevated plasma lactate (P = 0.001) and glucose (P = 0.007). MVC was higher for terbutaline than placebo (738 ± 64 vs. 681 ± 68 N) (P = 0.007). In addition, Wingate peak power and mean power were 2.2 ± 0.8 (P = 0.019) and 3.3 ± 1.0 % (P = 0.009) higher for terbutaline than placebo. Net accumulation of plasma lactate was higher (P = 0.003) for terbutaline than placebo during the Wingate test, whereas \(\dot{V}O_{2}\) above baseline was unchanged by terbutaline (P = 0.882). Time-trial performance was not different between treatments (P = 0.236).

Conclusion

High-dose inhaled terbutaline elicits a systemic response that enhances muscle strength and sprint performance. High-dose terbutaline should therefore continue to be restricted in competitive sport.