Autoantibodies are major predictors of arthritis development in patients with anti-citrullinated protein antibodies and musculoskeletal pain.

Objectives: Predictors of arthritis development are highly warranted among patients with anti-citrullinated protein antibodies (ACPAs) and musculoskeletal symptoms to optimize clinical management. We aimed to identify clinical and laboratory predictors of arthritis development, including biochemically assessed alcohol consumption, among ACPA-positive patients with musculoskeletal pain.Method: 82 ACPA-positive individuals with musculoskeletal pain but no clinical arthritis were followed for a median of 72 months (interquartile range 57-81 months). We evaluated the prognostic value of baseline clinical and laboratory factors including smoking, symptom duration, age, gender, shared epitope, rheumatoid factor (RF), anti-carbamylated protein antibodies, ACPA levels, erythrocyte sedimentation rate, C-reactive protein levels, tender joint count, patient-reported general well-being, 28-joint Disease Activity Score, and alcohol consumption as measured by phosphatidyl ethanol (PEth) levels in whole blood.Results: During follow-up, 48% developed at least one arthritis. Multivariable analysis revealed an increased risk of arthritis development with RF positivity [hazard ratio (HR) = 2.3, 95% confidence interval (CI) 1.1-4.8, p = 0.028] and higher ACPA levels (HR = 1.0, 95% CI 1.000-1.001, p = 0.002). High levels of RF (HR = 4.4, 95% CI 1.7-11) entailed the highest HR in this ACPA-positive population. Neither clinical characteristics nor alcohol consumption measured by PEth conferred significant prognostic value.Conclusions: ACPA levels and concurrent presence of RF are independent predictors of arthritis development among ACPA-positive patients with musculoskeletal pain. The results are compatible with a dose-response relationship between RA-related autoantibodies and risk of arthritis development.

Plasma concentrations of etonogestrel in women using oral desogestrel before and after Roux-en-Y gastric bypass surgery: a pharmacokinetic study.

OBJECTIVE: To investigate whether Roux-en-Y gastric bypass (RYGB) affects oral desogestrel (etonogestrel) pharmacokinetics. DESIGN: Single centre, open label, phase-2 pharmacokinetic study. SETTING: University hospital of Linköping, Sweden. POPULATION: Fourteen women with planned RYGB surgery were included; nine women aged 18-45 years using 75 micrograms desogestrel completed the study. METHODS: Steady-state etonogestrel pharmacokinetic (PK) parameters were measured on three occasions for each individual (at 8 ± 6 weeks before surgery, and at 12 ± 2 and 52 ± 2 weeks after surgery). Each patient served as her own control. On each occasion, serum samples were collected during a 24-hour period and etonogestrel concentrations were determined with ultra-performance liquid chromatography/tandem mass spectrometry. MAIN OUTCOME MEASURES: Area under the plasma concentration time curve of etonogestrel (AUC0-24 hours ). RESULTS: All women had significant postoperative weight loss. There were no significant differences in AUC0-24 hours , terminal half-lives (t½ ), time to peak serum concentrations (Tmax ), or apparent oral clearances of etonogestrel (CLoral ) before and after gastric bypass surgery on any occasion. Peak serum concentrations (Cmax ) increased after 52 ± 2 weeks compared with preoperative values (0.817 ng/ml versus 0.590 ng/ml, P = 0.024). CONCLUSION: To our knowledge, this is the first study to investigate the effects on desogestrel pharmacokinetics after RYGB. This study did not reveal any clinically significant changes in etonogestrel pharmacokinetics, suggesting that oral desogestrel may be used by women after RYGB surgery. The sample size was limited, however, and therefore the results should be interpreted cautiously. TWEETABLE ABSTRACT: The pharmacokinetics of oral desogestrel does not appear to change after gastric bypass surgery.