Correlation of mucosal healing endpoints with long-term clinical and patient-reported outcomes in ulcerative colitis.

BACKGROUND: We evaluated the clinical relevance of achieving histologic endoscopic mucosal improvement (HEMI) and the more stringent target of histologic endoscopic mucosal remission (HEMR) in the phase 3 maintenance trial of upadacitinib for moderately to severely active ulcerative colitis. METHODS: Clinical and patient-reported outcomes were assessed in patients with clinical response after 8- or 16-week upadacitinib induction who received 52-week upadacitinib maintenance treatment. Cross-sectional and predictive analyses evaluated the relationship between HEMR or HEMI at Week 8/16 and Week 52, respectively, and outcomes at Week 52. Adjusted odds ratios (aOR) were derived from logistic regressions for patients achieving HEMR or HEMI without HEMR versus those not achieving HEMI. RESULTS: Cross-sectional analyses showed that patients with HEMR had greater odds of achieving all clinical and patient-reported outcomes at Week 52 than those not achieving HEMI. In predictive analyses, patients with HEMR at Week 8/16 had significantly greater odds of achieving clinical remission (aOR = 3.6, p = 0.001) and endoscopic remission (aOR = 3.9, p < 0.001) at Week 52 than patients not achieving HEMI and HEMR. For patients achieving HEMI without HEMR, these odds were lower: clinical remission (aOR = 3.2, p < 0.001) and endoscopic remission (aOR = 2.4, p = 0.010). The odds of achieving clinically meaningful improvements in most patient-reported outcomes were directionally similar between HEMI and HEMR, but not statistically different to patients not achieving HEMI. No hospitalizations or surgeries were observed in patients with HEMR at Week 52. CONCLUSIONS: Achievement of HEMR or HEMI is clinically relevant with HEMR being associated with greater likelihood of improvement in long-term clinical and patient-reported outcomes. https://www. CLINICALTRIALS: gov NCT02819635.

A Comparative Evaluation of the Measurement Properties of Three Histological Indices of Mucosal Healing in Ulcerative Colitis: Geboes Score, Robarts Histopathology Index and Nancy Index.

BACKGROUND AND AIMS: To inform their future use in regulated clinical trials to evaluate treatment efficacy hypotheses, the measurement properties of three histological indices, Geboes Score [GS], Robarts Histopathology Index [RHI] and Nancy Index [NI], were evaluated among patients with ulcerative colitis. METHODS: Analyses were conducted on data from a Phase 3 clinical trial of adalimumab [M14-033, n = 491] and focused on evaluating the measurement properties of the GS, RHI and NI. Specifically, internal consistency and inter-rater reliability, convergent, discriminant and known-group validity, and sensitivity to change were assessed at Baseline, and at Weeks 8 and 52. RESULTS: Internal consistency for the RHI showed lower alpha [α] values at Baseline [α = 0.62] relative to Weeks 8 [α = 0.82] and 52 [α = 0.81]. The inter-rater reliability values of RHI [0.91], NI [0.64] and GS [0.53] were excellent, good and fair, respectively. Regarding validity, Week 52 correlations were moderate to strong between full and partial Mayo scores and Mayo subscale scores and the RHI and GS, and were weak to moderate for the NI. Significant differences between mean scores of all three histological indices were observed across known-groups based on Mayo endoscopy subscores and full Mayo scores at Weeks 8 and 52 [p < 0.001]. CONCLUSIONS: The GS, RHI and NI are each capable of producing reliable and valid scores that are sensitive to changes in disease activity over time, in patients with moderately to severely active ulcerative colitis. While all three indices demonstrated relatively acceptable measurement properties, the GS and RHI performed better than the NI.

Development and testing of an alternative responder definition for EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI).

OBJECTIVES: Dryness, fatigue and joint/muscle pain are typically assessed in Sjögren's trials using European Alliance of Associations for Rheumatology Sjögren's Syndrome Patient Reported Index (ESSPRI). A Patient Acceptable Symptom State of <5 and a Minimal Clinically Important Improvement (MCII)/responder definition (RD) of ≥1 point or 15% on ESSPRI have previously been defined. This study explored alternative RDs to better discriminate between active treatment and placebo in trials. METHODS: Anchor-based and distribution-based methods were used to derive RD thresholds in blinded phase IIb trial data (N=190) and confirm these in blinded data pooled from three early phase II trials (N=126). The populations consisted of individuals with moderate-to-severe systemic primary Sjögren's. Anchors were prioritised by ESSPRI correlations and used in similar conditions. Triangulated estimates were discussed with experts (N=3). The revised RD was compared with the original using unblinded data to assess placebo and treatment responder rates. RESULTS: Patients were predominantly female (>90%), white (90%), with mean age of 50 years. Receiver operating characteristic estimates supported an MCII threshold of 1.5-1.6 in the phase II data, whereas correlation-weighted mean change estimates supported a low/minimal symptom severity threshold of ≥2. A low/minimal symptom severity of ≤3 showed the greatest sensitivity/specificity balance. Analyses in the pooled data supported these thresholds (MCII: 1.5-2.1; low/minimal symptom severity: 2.7-3.7). Unblinded analyses confirmed the revised RD reduced placebo rates. CONCLUSIONS: Completing a trial with an improvement of ≥1.5 points compared with baseline and an ESSPRI score of ≤3 points is a relevant RD for moderate-to-severe systemic Sjögren's and reduces placebo rates.

Relationship between COMLEX-USA scores and performance on the American Osteopathic Board of Emergency Medicine Part I certifying examination.

CONTEXT: Few studies have investigated how well scores from the Comprehensive Osteopathic Medical Licensing Examination-USA (COMLEX-USA) series predict resident outcomes, such as performance on board certification examinations. OBJECTIVES: To determine how well COMLEX-USA predicts performance on the American Osteopathic Board of Emergency Medicine (AOBEM) Part I certification examination. METHODS: The target study population was first-time examinees who took AOBEM Part I in 2011 and 2012 with matched performances on COMLEX-USA Level 1, Level 2-Cognitive Evaluation (CE), and Level 3. Pearson correlations were computed between AOBEM Part I first-attempt scores and COMLEX-USA performances to measure the association between these examinations. Stepwise linear regression analysis was conducted to predict AOBEM Part I scores by the 3 COMLEX-USA scores. An independent t test was conducted to compare mean COMLEX-USA performances between candidates who passed and who failed AOBEM Part I, and a stepwise logistic regression analysis was used to predict the log-odds of passing AOBEM Part I on the basis of COMLEX-USA scores. RESULTS: Scores from AOBEM Part I had the highest correlation with COMLEX-USA Level 3 scores (.57) and slightly lower correlation with COMLEX-USA Level 2-CE scores (.53). The lowest correlation was between AOBEM Part I and COMLEX-USA Level 1 scores (.47). According to the stepwise regression model, COMLEX-USA Level 1 and Level 2-CE scores, which residency programs often use as selection criteria, together explained 30% of variance in AOBEM Part I scores. Adding Level 3 scores explained 37% of variance. The independent t test indicated that the 397 examinees passing AOBEM Part I performed significantly better than the 54 examinees failing AOBEM Part I in all 3 COMLEX-USA levels (P<.001 for all 3 levels). The logistic regression model showed that COMLEX-USA Level 1 and Level 3 scores predicted the log-odds of passing AOBEM Part I (P=.03 and P<.001, respectively). CONCLUSION: The present study empirically supported the predictive and discriminant validities of the COMLEX-USA series in relation to the AOBEM Part I certification examination. Although residency programs may use COMLEX-USA Level 1 and Level 2-CE scores as partial criteria in selecting residents, Level 3 scores, though typically not available at the time of application, are actually the most statistically related to performances on AOBEM Part I.