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GBT is an effective and safe recipe for the treatment of osteoarthritis of knee joint, which could alleviate the joint pain, stiffness, and dysfunction.

Introduction Total glucosides of paeony (TGP) is a natural plant extract, which is widely used in China for treating rheumatoid arthritis (RA). Many relevant randomised controlled trials (RCTs) of TGP for RA are available, but they have not been systematically reviewed. This systematic review aims to examine the effectiveness and safety of TGP in patients with RA. Methods and analyses We will search for RCTs of TGP in the treatment of RA, performed up until February 2016, in PubMed, Embase, Cochrane Central Register of Controlled Trials, and four Chinese databases (Chinese Biomedical Database, China National Knowledge Infrastructure, Wanfang Database and Chinese Scientific Journal Database). Trial registers and reference lists of retrieved articles will also be searched to identify potential articles. RCTs comparing TGP with placebo, no treatment, or disease-modifying antirheumatic drugs for patients with RA will be retrieved. The primary outcomes will be disease improvement and disease remission. The secondary outcomes will be surrogate outcomes, symptoms, adverse effects, and quality of life. Two reviewers will independently extract data on participants, interventions, comparisons, outcomes, etc. The methodological quality of each included study will be evaluated using the Cochrane risk of bias tool, and the strength of evidence on prespecified outcomes will be assessed in accordance with the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Review Manager 5.3 software will be used for data analyses. Meta-analyses will be performed if the data are sufficiently homogeneous, both statistically and clinically. Possible publication bias will also be checked using funnel plots once the number of included studies is sufficient. Ethics and dissemination Ethics approval is not required, as this study will not involve patients. The results of this study will be submitted to a peer-reviewed journal for publication, to inform both clinical practice and further research. Trial registration number CRD42015026345.

BackgroundMavrilimumab, a fully human monoclonal antibody targeting the granulocyte-macrophage colony-stimulating factor receptor (GM–CSFR) α, is in Phase IIb investigation for the treatment of rheumatoid arthritis (RA).ObjectivesWe characterized the exposure–efficacy relationship of mavrilimumab with data from two Phase II randomized controlled trials of patients with moderate to severe RA, via population modeling and clinical simulations.MethodsIn a Phase IIa study, adult patients with active RA received 7 subcutaneous administrations of mavrilimumab (10, 30, 50 or 100 mg every other week [eow]). Mavrilimumab pharmacokinetics and efficacy (DAS28–CRP, ACR20/50) were modeled using a population approach. Clinical simulations were performed to facilitate the design of a Phase IIb trial, in which RA patients received placebo or mavrilimumab (30, 100, or 150 mg eow) for 24 weeks. We developed a joint probability model to describe the risk of voluntary dropouts at each scheduled visit of the Phase IIb study. The exposure–response relationship for mavrilimumab was characterized by clinical simulations via the PK-efficacy dropout model.ResultsMavrilimumab and placebo treatment effects observed in the Phase IIa study were adequately described by mechanistic PK-efficacy model. Although mavrilimumab 150 mg eow was not evaluated in the Phase IIa study, improved efficacy was observed at this dosage in Phase IIb, as predicted by a priori clinical simulations. The hazard rate of patient dropout prior to next scheduled visits was significantly greater for non-responders, and substantially greater for lower dosage groups at Week 12, when patient rollover to an open-label extension study was permitted. Clinical simulations indicated that the maximum efficacy was reached at the 150-mg eow dosage.ConclusionsEfficacy outcomes of the Phase IIb study confirmed the rational selection of mavrilimumab 150 mg eow as the best dosage, through modeling of Phase IIa data. Joint modeling of placebo effect, treatment response, and informative dropout greatly facilitates interpretation of Phase IIb results, and will assist in the design of late-stage clinical trials for mavrilimumab.Disclosure of InterestD. Jin Shareholder of: AstraZeneca, Employee of: MedImmune, C.-Y. Wu Shareholder of: AstraZeneca, Employee of: MedImmune, L. Roskos Shareholder of: AstraZeneca, Employee of: MedImmune, A. Godwood Shareholder of: AstraZeneca, Employee of: MedImmune, D. Close Shareholder of: AstraZeneca, Employee of: MedImmune, B. Wang Shareholder of: AstraZeneca, Employee of: MedImmune

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