Week 2 Adalimumab Levels Predict Short-term Clinical Remission in Patients With Inflammatory Bowel Disease.

BACKGROUND AND GOALS: The role of early proactive therapeutic drug level monitoring for anti-tumor necrosis factor therapies is unclear. We aimed to determine whether a week 2 serum trough level in patients with inflammatory bowel disease (IBD) using adalimumab may predict clinical outcomes. MATERIALS AND METHODS: This was a retrospective study of consecutive IBD patients with a week 2 serum adalimumab level available. Receiver operating characteristic curve analysis was conducted to determine an optimal week 2 threshold level for adalimumab. Patients above the threshold were compared for the primary outcome of week 12 clinical remission (CR) and the secondary outcome of short-term endoscopic healing. Multivariate logistic regression analysis was performed to evaluate the relationship between week 2 adalimumab level and CR. RESULTS: Forty-six patients had a week 2 adalimumab level performed. Receiver operating characteristic curve analysis suggested an optimal adalimumab level of 11.9 mcg/mL based on the area under the curve. Patients with week 2 adalimumab levels >11.9 mcg/mL had higher odds of week 12 CR than those with levels below or equal to this threshold (odds ratio=3.34, 95% confidence interval: 1.01-12.11, P =0.04). Other covariates were not found to have a significant association with the primary outcome. The rate of short-term endoscopic healing was numerically higher in patients with adalimumab week 2 levels above 11.9 mcg/mL; however, was not statistically significant (71.4% vs. 28.5%, P =0.11). CONCLUSIONS: Serum adalimumab levels at week 2 appears to be a predictor of short-term CR. Further research should explore whether patients with a week 2 adalimumab level equal to or below 11.9 mcg/mL benefit from early dose optimization.

Getting fit for hip and knee replacement: a protocol for the Fit-Joints pilot randomized controlled trial of a multi-modal intervention in frail patients with osteoarthritis.

BACKGROUND: Joint replacement provides significant improvements in pain, physical function, and quality of life in patients with osteoarthritis. With a growing body of evidence indicating that frailty can be treated, it is important to determine whether targeting frailty reduction in hip and knee replacement patients improves post-operative outcomes. OBJECTIVES: The primary objective is to examine the feasibility of a parallel group RCT comparing a preoperative multi-modal frailty intervention to usual care in pre-frail/frail older adults undergoing elective unilateral hip or knee replacements. The secondary objectives areTo explore potential efficacy of the multi-modal frailty intervention in improving frailty and mobility between baseline and 6 weeks post-surgery using Fried frailty phenotype and short performance physical battery (SPPB) respectively.To explore potential efficacy of the multi-modal frailty intervention on post-operative healthcare services use. METHODS/DESIGN: In a parallel group pilot RCT, participants will be recruited from the Regional Joint Assessment Program in Hamilton, Canada. Participants who are (1) ≥ 60 years old; (2) pre-frail (score of 1 or 2) or frail (score of 3-5; Fried frailty phenotype); (3) having elective unilateral hip or knee replacement; and (4) having surgery wait times between 3 and 10 months will be recruited and randomized to either the intervention or usual care group. The multi-modal frailty intervention components will include (1) tailored exercise program (center-based and/or home-based) with education and cognitive behavioral change strategies; (2) protein supplementation; (3) vitamin D supplementation; and (4) medication review. The main comparative analysis will take place at 6 weeks post-operative. The outcome assessors, data entry personnel, and data analysts are blinded to treatment allocation. Assessments: feasibility will be assessed by recruitment rate, retention rate, and data collection completion. Frailty and healthcare use and other clinical outcomes will be assessed. The study outcomes will be collected at the baseline, 1 week pre-operative, and 6 weeks and 6 months post-operative. DISCUSSION: This is the first study to examine the feasibility of multi-modal frailty intervention in pre-frail/frail older adults undergoing hip or knee replacement. This study will inform the planning and designing of multi-modal frailty interventional studies in hip and knee replacement patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02885337.