The impact of ustekinumab on extraintestinal manifestations of Crohn's disease: A post hoc analysis of the UNITI studies.

This post hoc analysis of the UNITI studies found ustekinumab (UST) did not significantly improve overall extraintestinal manifestations (EIMs) of Crohn's disease compared to placebo-treated patients at weeks 6 and 52. BACKGROUND AND AIMS: The UNITI trials demonstrated that UST was effective in inducing and maintaining clinical remission in Crohn's disease (CD). However, limited data exists regarding its effectiveness for treatment of EIMs. This post hoc analysis evaluated the efficacy of UST in treatment of EIMs. METHODS: Data from UNITI-1/2 and IM-UNITI (NCT01369329, NCT01369342, NCT01369355) were obtained from the Yale Open Data Access Project (2019-4104). Nine hundred and fourty-one patients eligible for UST induction and 263 patients eligible for maintenance UST were included. The primary outcome of interest was EIM resolution at Week 6 in UST and placebo-treated patients using the chi-square test. EIM resolution at Week 52 was also assessed. McNemar's test was used to compare the proportion of patients who reported active EIMs at weeks 6 and 52 versus baseline. RESULTS: From 941 UST-treated patients in UNITI-1/2, 504 had 527 EIMs at baseline. Overall, there was no significant difference in EIM resolution observed in UST-treated patients (186/504, 36.9%) compared to placebo (90/230, 39.1%; p = 0.564) at Week 6. Patients treated with continuous UST (91/119, 76.4%) had no significant difference in overall EIMs resolved at Week 52 compared to placebo (72/90, 80.0%; p = 0.542). Although many EIMs demonstrated reduction in prevalence compared to baseline at initiation of UST, only erythema nodosum was more likely to improve at Week 52 on treatment versus placebo. CONCLUSION: Overall, UST did not lead to significant resolution of EIMs for CD compared to placebo at weeks 6 and 52.

Histologic remission does not offer additional benefit for ulcerative colitis patients in endoscopic remission.

BACKGROUND: Histologic remission in ulcerative colitis (UC) patients may be associated with positive outcomes. It is unclear whether UC patients in endoscopic remission obtain additional benefit from achieving histologic remission. AIM: To evaluate the relationship between time to relapse and histological activity among UC patients in endoscopic remission. METHODS: In this retrospective study using an observational database, we identified UC patients who had achieved endoscopic remission (Mayo endoscopic subscore 0). Index colonoscopy was the first colonoscopy when endoscopic remission was achieved. Histologic activity was classified as normal, inactive or active colitis. The primary outcome was time to relapse. Secondary outcomes included reasons for relapse and the association between baseline variables and risk of relapse. A Cox proportional hazards model evaluated baseline factors and the outcome of relapse. RESULTS: We included 269 patients. The Kaplan-Meier survival curve showed no significant difference between the presence or absence of histologic activity and time to relapse (log rank P = 0.85). There was no difference in time to clinical relapse of patients with histologically active colitis compared to inactive colitis (adjusted hazard ratio [AHR] 1.17, 95% CI 0.58-2.32, P = 0.67]). 5-aminosalicylate use (AHR 0.42, 95% CI 0.21-0.82, P = 0.011), pancolitis (AHR 0.32, 95% CI 0.13-0.75, P = 0.008), left-sided colitis (AHR 0.46; 95% CI 0.22-0.98; P = 0.044) and older age (AHR 0.96, 95% CI 0.94-0.99, P = 0.002) were significantly associated with reduced time to clinical relapse. CONCLUSION: Histologic remission did not influence time to relapse in UC patients who had achieved endoscopic remission.

Efficacy of antimicrobial photodynamic therapy against halitosis in adolescent patients undergoing orthodontic treatment.

PURPOSE: The aim of the present randomized controlled clinical trial was to evaluate the efficacy of photodynamic therapy (PDT) on halitosis in adolescent patients undergoing fixed orthodontic treatment. MATERIALS AND METHODS: Forty-five adolescents with halitosis undergoing orthodontic treatment were equally randomized into three groups: Group - I: provision of treatment through PDT on dorsum of tongue; Group - II: provision of treatment with the help of tongue scrappers (TS); Group - III: provision of treatment with the help of TS and adjunctive PDT. Presence of halitosis confirmed on the basis of gas chromatography and estimation of oral malodour with a cysteine challenge and H2S values recorded ≥112 parts per billion (ppb). A portable device Oral Chroma™ was used for performing breath analysis. A total of 5 bacterial species including P. gingivalis, F. nucleatum, P. intermedia, T. forsythia and T. denticola were studied as the proportion of sites defined as having ≥1.0 × 105 bacterial cells. RESULTS: The mean age of the participants in Group-I, II and III were 15.4 years, 13.8 years, and 14.2 years, respectively. The median values for Group-I, II and III at initial breath analysis were 874 ppb, 613 ppb and 1089 ppb, respectively. After treatment with the respective therapeutic modalities, a statistically significant difference was seen among groups after 2-weeks (p < 0.0001) (Table 3). After applying Kruskal-Wallis test, group-III showed the highest amount of reduction in H2S concentration (100 %) at final 2-weeks breath analysis compared to group-I and group-II (p = 0.0001). Descriptive statistics for all bacteria showed that group-III (TS + PDT) statistically significantly reduced the proportional distribution of all bacteria at 2-week follow-up (p < 0.0001) compared to group-I or group-II. CONCLUSION: PDT along with tongue scrapping showed effective immediate reduction of H2S concentration and reduction of oral pathogens in adolescent patients undergoing fixed orthodontic treatment with short-term follow up. Long-term evaluation and complete eradication of halitosis needs to be explored in further clinical trials. In addition, the cost of PDT and its potential side effects should not be disregarded.

Patient-Reported Outcomes and Endoscopic Appearance of Ulcerative Colitis: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: We aimed to evaluate the association of the patient-reported outcomes for rectal bleeding and stool frequency among patients with ulcerative colitis (UC) in endoscopic remission. METHODS: We performed a systematic review of studies reporting the association of patient-reported outcomes (the patient-reported components of the Mayo score: rectal bleeding and stool frequency) and endoscopic remission (Mayo endoscopic subscore of 0 or 1). We performed a meta-analysis of diagnostic accuracy using the hierarchical bivariate method. RESULTS: Our meta-analysis consisted of 5 studies comprising 2132 participants. A rectal bleeding subscore of 0 identified patients in endoscopic remission with a pooled sensitivity value of 81% (95% CI, 73%-86%), a specificity value of 68% (95% CI, 61%-75%), a positive likelihood ratio (LR) of 2.5 (95% CI, 2.2-3.0), and a negative LR of 0.28 (95% CI, 0.22-0.37). A stool frequency subscore of 0 identified patients in endoscopic remission with a pooled sensitivity value of 40% (95% CI, 25%-58%), a specificity value of 93% (95% CI, 86%-97%), a positive LR of 6.0 (95% CI, 3.7-9.7), and negative LR of 0.64 (95% CI, 0.50-0.82). A combined rectal bleeding and stool frequency subscore of 0 identified patients in endoscopic remission with a pooled sensitivity value of 36% (95% CI, 22%-54%), a specificity value of 96% (95% CI, 91%-98%), a positive LR or 8.4 (95% CI, 5.5-12.8), and a negative LR or 0.66 (95% CI, 0.53-0.84). CONCLUSIONS: In a meta-analysis of 5 studies, we found that most patients with UC and normal rectal bleeding and stool frequency subscores have attained endoscopic remission. Many patients in endoscopic remission from UC have no rectal bleeding. Normal stool frequency associates with endoscopic remission, but many patients have abnormal stool frequencies despite endoscopic remission. These results should be carefully considered given the high heterogeneity and wide confidence intervals for some outcomes.