Anrukinzumab, an anti-interleukin 13 monoclonal antibody, in active UC: efficacy and safety from a phase IIa randomised multicentre study.

OBJECTIVE: Interleukin 13 (IL-13) is thought to play a key role as an effector cytokine in UC. Anrukinzumab, a humanised antibody that inhibits human IL-13, was evaluated for the treatment of UC. DESIGN: In a multicentre, randomised, double-blind, placebo-controlled study, patients with active UC (Mayo score ≥4 and <10) were randomised to anrukinzumab 200, 400 or 600 mg or placebo. Patients received five intravenous administrations over 14 weeks. The primary endpoint was fold change from baseline in faecal calprotectin (FC) at Week 14. Secondary endpoints included safety, pharmacokinetics and IL-13 levels. RESULTS: The modified intention-to-treat population included 84 patients (21 patients/arm). Fold change of FC from baseline at Week 14 was not significantly different for any treatment groups compared with the placebo. The study had a high dropout rate, in part, related to lack of efficacy. The exploratory comparisons of each dose were not significantly different from placebo in terms of change from baseline in total Mayo score, clinical response, clinical remission and proportion of subjects with mucosal healing. An increase in serum total IL-13 (free and bound to anrukinzumab) was observed for all anrukinzumab groups but not with placebo. This suggests significant binding of anrukinzumab to IL-13. The safety profile was not different between the anrukinzumab and placebo groups. CONCLUSIONS: A statistically significant therapeutic effect of anrukinzumab could not be demonstrated in patients with active UC in spite of binding of anrukinzumab to IL-13. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number NCT01284062.

Assessment of rotator cuff repair integrity using ultrasound and magnetic resonance imaging in a multicenter study.

BACKGROUND: This study compared ultrasound and magnetic resonance imaging (MRI) evaluation of the repaired rotator cuff to determine concordance between these imaging studies. METHODS: We performed a concordance study using the data from a prospective nonrandomized multicenter study at 13 centers. A suture bridge technique was used to repair 113 rotator cuff tears that were between 1 and 4 cm wide. Repairs were evaluated with MRI and ultrasound at multiple time points after surgery. The MRI scans were read by a central radiologist and the surgeon, and the ultrasounds were read by a local radiologist or the surgeon who performed the ultrasound. RESULTS: The concordance between the central radiologist's MRI reading and the investigator's MRI readings at all time points was 89%, with a κ coefficient of 0.60. The concordance between the central radiologist's MRI and ultrasound readings at all time points was 85%, with a κ coefficient of 0.40. The concordance between the investigator's MRI and ultrasound readings was 92%, with a κ coefficient of 0.70. CONCLUSIONS: In the community setting, ultrasound may be used to evaluate the integrity of a repaired rotator cuff tendon and constitutes a comparable alternative to MRI when evaluating the integrity of a rotator cuff repair. Clinical investigators should compare their postoperative ultrasound results with their postoperative MRI results for a certain time period to establish the accuracy of ultrasound before relying solely on ultrasound imaging to evaluate the integrity of their rotator cuff repairs.

Importance of pharmacokinetic profile and timing of coadministration of short- and long-acting formulations of methylphenidate on patterns of subjective responses and abuse potential.

OBJECTIVE: Subjective responses (ie, liking, disliking) to stimulants are thought to be proxies for abuse potential. Greater subjective responses have been documented in formulations that are more rapidly absorbed. However, repeat dosing has not been examined. METHODS: Subjective responses on the Drug Rating Questionnaire were compared in 26 healthy adults after administration of short- (immediate-release [IR] methylphenidate [MPH]) and long- (osmotically controlled-release oral delivery system [OROS] MPH) acting stimulant formulations. The second dose was administered 4 hours after initial dosing. All subjects received all 5 conditions (ie, placebo to placebo; IR-MPH to IR-MPH; IR-MPH to OROS-MPH; OROS-MPH to IR-MPH; or OROS-MPH to OROS-MPH) in a double-blind, counter-balanced design on 5 separate days. RESULTS: Plasma levels and subjective patterns of detection were higher when an IR formulation was administered during the ascending phase of a first-administered long-acting dose (OROS). CONCLUSION: These results emphasize the critical role that formulation type (IR vs OROS) and timing of administration (ascending vs descending phase) play when short- and long-acting formulations are coadministered. Such knowledge provides important information for clinicians about the safety and tolerability of the timing of repeat dosing of various permutations of coadministration of MPH formulations.