A Practical guide to selecting and using new Crohn's disease therapies.

PURPOSE OF REVIEW: This review details the three new agents, including two novel mechanisms of action, approved to treat Crohn's disease in recent years. We review efficacy, safety, prescribing information, and available data on positioning these new therapies. RECENT FINDINGS: Risankizumab and upadacitinib are novel mechanisms of action approved to treat moderate to severe Crohn's disease. Risankizumab targets the cytokine interleukin-23. Upadacitinib is a selective Janus kinase-1 inhibitor approved for use in individuals who have previously failed or are intolerant to an anti-TNF agent. Subcutaneous infliximab provides a novel method of administering maintenance dosing of a longstanding and efficacious therapy. SUMMARY: Risankizumab has shown efficacy in both biologic naïve and biologic experienced populations. The SEQUENCE trial shows superiority of risankizumab over ustekinumab for disease response in patients who have previously failed an anti-tumor necrosis factor agent. Upadacitinib has shown good efficacy in clinical trials even in the setting of a mandated steroid taper during induction. Subcutaneous infliximab maintenance therapy appears noninferior to i.v. infliximab and shows good treatment persistence in real world transitions. Additional data is needed to better understand how to position these therapies.

Insurance Approval Delay of Biologic Therapy Dose Escalation Associated with Disease Activity in Patients with Inflammatory Bowel Disease.

BACKGROUND: Dose escalation of self-injectable biologic therapy for inflammatory bowel diseases may be required to counteract loss of response and/or low drug levels. Payors often require completion of a prior authorization (PA), which is a complex approval pathway before providing coverage. If the initial PA request is denied, clinic staff must complete a time and resource-intensive process to obtain medication approval. AIMS: This study measured time from decision to dose escalate to insurance approval and evaluated impact of approval time on disease activity. METHODS: This was a single-center retrospective analysis of adult patients with IBD prescribed an escalated dose of biologic therapy at an academic center with an integrated specialty pharmacy team from January to December 2018. Outcomes included time to insurance approval and the association between approval time and follow-up C-reactive protein (CRP) and Short Inflammatory Bowel Disease Questionnaire (SIBDQ) scores. Associations were tested using linear regression analyses. RESULTS: 220 patients were included, median age 39, 53% female, and 96% white. Overall median time from decision to dose escalate to insurance approval was 7 days [interquartile range (IQR) 1, 14]. Approval time was delayed when an appeal was required [median of 29 days (IQR 17, 43)]. Patients with a longer time to insurance approval were less likely to have CRP improvement (p = 0.019). Time to insurance approval did not significantly impact follow-up SIBDQ scores. CONCLUSION: Patients who had a longer time to insurance approval were less likely to have improvement in CRP, highlighting the negative clinical impact of a complex dose escalation process.

A Randomized Trial Comparing the Specific Carbohydrate Diet to a Mediterranean Diet in Adults With Crohn's Disease.

BACKGROUND & AIMS: This study compared the effectiveness of the Specific Carbohydrate Diet (SCD) to the Mediterranean diet (MD) as treatment for Crohn's disease (CD) with mild to moderate symptoms. METHODS: Adult patients with CD and with mild-to-moderate symptoms were randomly assigned 1:1 to consume the MD or SCD for 12 weeks. For the first 6 weeks, participants received prepared meals and snacks according to their assigned diet. After 6 weeks, participants were instructed to follow the diet independently. The primary outcome was symptomatic remission at week 6. Key secondary outcomes at week 6 included fecal calprotectin (FC) response (FC <250 µg/g and reduction by >50% among those with baseline FC >250 µg/g) and C-reactive protein (CRP) response (high-sensitivity CRP <5 mg/L and >50% reduction from baseline among those with high-sensitivity CRP >5 mg/L). RESULTS: The study randomized 194 patients, and 191 were included in the efficacy analyses. The percentage of participants who achieved symptomatic remission at week 6 was not superior with the SCD (SCD, 46.5%; MD, 43.5%; P = .77). FC response was achieved in 8 of 23 participants (34.8%) with the SCD and in 4 of 13 participants (30.8%) with the MD (P = .83). CRP response was achieved in 2 of 37 participants (5.4%) with the SCD and in 1 of 28 participants (3.6%) with the MD (P = .68). CONCLUSIONS: The SCD was not superior to the MD to achieve symptomatic remission, FC response, and CRP response. CRP response was uncommon. Given these results, the greater ease of following the MD and other health benefits associated with the MD, the MD may be preferred to the SCD for most patients with CD with mild to moderate symptoms. ClinicalTrials.gov Identifier: NCT03058679.

Mucosal Integrity Testing Can Detect Differences in the Rectums of Patients with Inflammatory Bowel Disease Compared to Controls: A Pilot Study.

BACKGROUND: While the pathogenesis of inflammatory bowel disease (IBD) is incompletely understood, disruption of epithelial integrity is suspected to play a prominent role in disease initiation and progression. Currently, there is no convenient way to measure this in vivo. AIMS: Our aim is to determine whether a mucosal integrity (MI) testing device that has been used to measure MI in the esophagus can also be used to measure barrier function in the colon during colonoscopy. METHODS: Mucosal integrity testing was measured in patients with IBD (n = 17) and controls (n = 7) during colonoscopy. During the procedure, an MI catheter was passed down the working channel of the colonoscope and placed along the mucosal wall to measure MI in the rectum, left, transverse, and right colon. In patients with IBD, MI measurements and biopsies were taken in areas which appeared inflamed when present. We then determined if there was a significant difference in MI between patients with IBD and controls. RESULTS: MI was significantly higher in the rectum of patients with IBD (CD and UC combined) versus control colons [767 (618-991) vs. 531 (418-604) ohms, P < 0.01]. There were no significant differences in MI among patients with IBD versus controls in the right, transverse, or left colon. Within the IBD group, there were no significant differences in MI between inflamed versus non-inflamed rectums. There was no correlation between quality of life scores or endoscopic severity with MI, though this study was likely underpowered to detect these differences. CONCLUSION: Rectal MI is significantly higher in patients with IBD versus controls. Future studies are needed to determine how this information can be used clinically.

Safety and Efficacy of Vedolizumab Versus Tumor Necrosis Factor α Antagonists in an Elderly IBD Population: A Single Institution Retrospective Experience.

BACKGROUND: Vedolizumab is a monoclonal antibody used to treat inflammatory bowel disease (IBD). There is little known about the safety and comparative efficacy of this agent in the elderly population. AIMS: Here, we present data on the safety and comparative efficacy of vedolizumab versus tumor necrosis factor α antagonists (anti-TNF) in elderly patients with IBD. METHODS: This retrospective cohort study included IBD patients started on vedolizumab or anti-TNF at age 60 or older at a single tertiary IBD center. Safety was evaluated by assessing for the development of serious infection. The comparative needs for IBD-related surgery, IBD-related hospitalization, and drug discontinuation for any reason were obtained. Efficacy was assessed by comparing changes in endoscopic, histologic, and patient-report outcomes. RESULTS: 212 cases were identified-108 patients treated with vedolizumab and 104 patients treated with anti-TNF. There were no significant differences between cohorts in serious infection, surgical intervention, or IBD-hospitalization-free survival (p = NS). Drug discontinuation survival was different between anti-TNF and vedolizumab (p = 0.02) with more patients remaining on vedolizumab at the time of last follow-up (51.9% vs. 25.9%). Endoscopic remission and response rates were higher in the vedolizumab versus anti-TNF group (65.7% vs. 45.2%, p = 0.02; 80.0% vs. 59.3%, p < 0.001). CONCLUSIONS: In a cohort of IBD patients over age 60, vedolizumab showed no statistically significant differences in infection, hospitalization, or surgical intervention-free survival as compared to anti-TNF. Vedolizumab was discontinued less frequently than anti-TNF. Patients on vedolizumab had higher rates of endoscopic remission and response.

Effect of TELEmedicine for Inflammatory Bowel Disease on Patient Activation and Self-Efficacy.

INTRODUCTION: Limitations in inflammatory bowel disease (IBD) care necessitate greater patient activation and self-efficacy, measures associated with positive health outcomes. METHODS: We assessed change in patient activation and general self-efficacy from baseline to 12 months through our TELEmedicine for IBD trial, a multicenter, randomized controlled trial consisting of a web-based monitoring system that interacts with participants via text messaging. A total of 222 adults with IBD who had experienced an IBD flare within 2 years prior to the trial were randomized into either a control arm that received standard care (SC) or an intervention arm that completed self-testing through the TELE-IBD system every other week (EOW) or weekly (W). RESULTS: Changes in self-efficacy scores were not significantly different between control and experimental groups. Patient activation scores were significantly different between standard care and the TELE-IBD EOW group only (p = 0.03). CONCLUSIONS: Use of remote monitoring did not improve self-efficacy or patient activation compared to routine care.

Correction to: Effect of TELEmedicine for Inflammatory Bowel Disease on Patient Activation and Self-Efficacy.

This manuscript is a secondary analysis of a large multicenter randomized controlled trial. The primary study is Cross RK et al., A Randomized Controlled Trial of TELEmedicine for patients with Inflammatory Bowel Disease (TELE-IBD). Am J Gastroenterol, 2019 Mar.

A Randomized Controlled Trial of TELEmedicine for Patients with Inflammatory Bowel Disease (TELE-IBD).

INTRODUCTION: Telemedicine has shown promise in inflammatory bowel disease (IBD). The objective of this study was to compare disease activity and quality of life (QoL) in a 1-year randomized trial of IBD patients receiving telemedicine vs. standard care. METHODS: Patients with worsening symptoms in the prior 2 years were eligible for randomization to telemedicine (monitoring via texts EOW or weekly) or standard care. The primary outcomes were the differences in change in disease activity and QoL between the groups; change in healthcare utilization among groups was a secondary aim. RESULTS: 348 participants were enrolled (117 control group, 115 TELE-IBD EOW, and 116 TELE-IBD weekly). 259 (74.4%) completed the study. Age was 38.9 ± 12.3 years, 56.6% were women, 91.9% were Caucasian, 67.9% had Crohn's disease (CD) and 42.5% had active disease at baseline. In CD, all groups experienced a decrease in disease activity (control -5.2 ± 5.0 to 3.7 ± 3.6, TELE-IBD EOW 4.7 ± 4.1 to 4.2 ± 3.9, and TELE-IBD weekly 4.2 ± 4.2 to 3.2 ± 3.4, p < 0.0001 for each of the groups) In UC, only controls had a significant decrease in disease activity (control 2.9 ± 3.1 to 1.4 ± 1.4, p = 0.01, TELE-IBD EOW 2.7 ± 3.1 to 1.7 ± 1.9, p = 0.35, and TELE-IBD Weekly 2.5 ± 2.5 to 2.0 ± 1.8, p = 0.31). QoL increased in all groups; the increase was significant only in TELE-IBD EOW (control 168.1 ± 34.0 to 179.3 ± 28.2, p = 0.06, TELE-IBD EOW 172.3 ± 33.1 to 181.5 ± 28.2, p = 0.03, and TELE-IBD Weekly 172.3 ± 34.5 to 179.2 ± 32.8, p = 0.10). Unadjusted and adjusted changes in disease activity and QoL were not significantly different among groups. Healthcare utilization increased in all groups. TELE-IBD weekly were less likely to have IBD-related hospitalizations and more likely to have non-invasive diagnostic tests and electronic encounters compared to controls; both TELE-IBD groups had decreased non-IBD related hospitalizations and increased telephone calls compared to controls. DISCUSSION: Disease activity and QoL, although improved in all participants, were not improved further through use of the TELE-IBD system. TELE-IBD participants experienced a decrease in hospitalizations with an associated increase in non-invasive diagnostic tests, telephone calls and electronic encounters. Research is needed to determine if TELE-IBD can be improved through patient engagement and whether it can decrease healthcare utilization by replacing standard care.

Depressive Symptoms Predict Anti-tumor Necrosis Factor Therapy Noncompliance in Patients with Inflammatory Bowel Disease.

BACKGROUND: Noncompliance in use of anti-tumor necrosis factor (anti-TNF) therapy in patients with moderate-to-severe inflammatory bowel disease (IBD) can be a factor in medication failure. Few studies have evaluated the contribution of depressive symptoms to medication noncompliance in anti-TNF therapies. METHODS: A retrospective chart review was performed in a single-center tertiary care IBD center for patients with Crohn's disease and ulcerative colitis starting anti-TNF therapy over a 2-year period. Medication noncompliance was defined as interruption of medication (not filling anti-TNF prescription if injectable or not getting infliximab infusion for 30 days beyond needed date for continuation) due to patient-driven circumstances. Depressive symptoms were evaluated at baseline using the well-validated Patient Health Questionnaire-9 (PHQ-9), with PHQ-9 ≥ 10 indicative of at least moderate depressive symptoms. Statistical analysis was performed using Cox proportional hazards regression controlling for age, sex, psychiatric history, and disease. RESULTS: A total of 246 patients (75 with ulcerative colitis, 171 with Crohn's disease) were started on anti-TNF therapy. Seventy-nine patients (32%) had a prior psychiatric diagnosis reported in the medical record. Thirty-three patients (13%) were noncompliant in follow-up. Sixty patients (24%) had at least moderate depressive symptoms at baseline (PHQ ≥ 10). Depressive symptoms at baseline were significantly associated with noncompliance in follow-up (hazards ratio 2.28, CI 1.1-4.6, p < 0.05). CONCLUSION: Depressive symptoms at baseline were associated with medication noncompliance of anti-TNF therapies at follow-up when controlling for age, sex, disease type, and history of psychiatric disease.

Association Between Affective-Cognitive Symptoms of Depression and Exacerbation of Crohn's Disease.

OBJECTIVES: The prevalence of depression is high in patients with Crohn's disease (CD). We examined the influence of affective-cognitive symptoms of depression on the risk of exacerbation of CD. METHODS: We studied 2,144 adult volunteers with a self-reported diagnosis of CD who completed a baseline survey that included demographics, CD status, and an affective-cognitive index of depression. Linear and logistic regression analyses were used to determine whether CD status at 12 months was associated with the baseline measure of depression. Analyses were adjusted for confounders including age, gender, race, baseline disease activity, disease duration, prior hospitalization and surgery, corticosteroid and anti-TNF use, medication adherence, body mass index, current smoking, education, and sleep quality. RESULTS: Depression was significantly associated with subsequent increases in SCDAI score in both unadjusted (P<0.001) and adjusted (P<0.001) analyses. This association was non-linear, with a shallower slope for lower levels of depression. A 10-point increase in depression t-scores from 55 to 65 was associated with a 18.6-point increase in SCDAI (95% CI 11.5-25.6) and an odds ratio of 1.27 for SCDAI>150 at follow-up (CI: 1.01-1.60). We also found a significant association between depressive symptoms and hospitalization. CONCLUSIONS: Cognitive-affective depressive symptoms were significantly associated with a risk of exacerbation of CD and hospitalization.

Treatment with immunosuppressive therapy may improve depressive symptoms in patients with inflammatory bowel disease.

INTRODUCTION: Recent research suggests a relationship of inflammatory bowel disease (IBD) and depression. Our objective was to evaluate for improvement of depressive symptoms with treatment of IBD using immunosuppressive medications. METHODS: A retrospective study of consecutive patients with IBD started on immunosuppressive agents [anti-tumor necrosis factor (anti-TNF) or immunomodulator therapy] was conducted. Patients were evaluated if disease activity indices using Harvey Bradshaw Index for Crohn's disease (CD) and Simple Clinical Colitis Disease Activity Index for ulcerative colitis (UC) and depressive indices using Patient Health Questionnaire-9 (PHQ-9) scores were obtained before and at least 30 days after initiation of therapy. RESULTS: Sixteen patients with UC and 53 patients with CD (all with active disease symptoms) were evaluated over a 60 day median follow-up evaluation (range 30, 140 days). Twenty-two patients started on immunomodulator therapy, and 47 patients started on anti-TNF therapy. Crohn's disease patients had significantly decreased PHQ-9 scores at follow-up [median 9 (range 3, 14) to 4 (1, 8)], with significant decreases only in those started on anti-TNF therapy. Changes in PHQ-9 and CRP were correlated (ρ = 0.38, p < 0.05). In patients with UC, PHQ-9 scores [5 (3, 9) to 2 (0, 5)] were significantly decreased. Percentage at risk of moderate to severe depression (PHQ-9 scores ≥10) was lower after treatment [Crohn's disease 51-18 % (p < 0.05), ulcerative colitis 18-0 %]. CONCLUSION: Depressive scores decreased significantly in patients with IBD treated with immunosuppressive therapy and the number at risk for moderate to severe depression improved significantly.

Predicting persistence of functional abdominal pain from childhood into young adulthood.

BACKGROUND & AIMS: Pediatric functional abdominal pain has been linked to functional gastrointestinal disorders (FGIDs) in adulthood, but little is known about patient characteristics in childhood that increase the risk for FGID in young adulthood. We investigated the contribution of gastrointestinal symptoms, extraintestinal somatic symptoms, and depressive symptoms in pediatric patients with functional abdominal pain and whether these predicted FGIDs later in life. METHODS: In a longitudinal study, consecutive new pediatric patients, diagnosed with functional abdominal pain in a subspecialty clinic, completed a comprehensive baseline evaluation of the severity of their physical and emotional symptoms. They were contacted 5 to 15 years later and evaluated, based on Rome III symptom criteria, for abdominal pain-related FGIDs, including irritable bowel syndrome, functional dyspepsia, functional abdominal pain syndrome, and abdominal migraine. Controlling for age, sex, baseline severity of abdominal pain, and time to follow-up evaluation, multivariable logistic regression was used to evaluate the association of baseline gastrointestinal, extraintestinal somatic, and depressive symptoms in childhood with FGID in adolescence and young adulthood. RESULTS: Of 392 patients interviewed an average of 9.2 years after their initial evaluation, 41% (n = 162) met symptom criteria for FGID; most met the criteria for irritable bowel syndrome. Extraintestinal somatic and depressive symptoms at the initial pediatric evaluation were significant predictors of FGID later in life, after controlling for initial levels of GI symptoms. Age, sex, and abdominal pain severity at initial presentation were not significant predictors of FGID later in life. CONCLUSIONS: In pediatric patients with functional abdominal pain, assessment of extraintestinal and depressive symptoms may be useful in identifying those at risk for FGID in adolescence and young adulthood.

Outcomes following infliximab therapy for pediatric patients hospitalized with refractory colitis-predominant IBD.

OBJECTIVES: Although randomized trials demonstrated the efficacy of infliximab for both pediatric Crohn disease and ulcerative colitis (UC), few patients in these studies exhibited colitis requiring hospitalization. The aims of this study were to determine the rate of subsequent infliximab failure and dose escalation in pediatric patients who started taking infliximab during hospitalization for colitis-predominant IBD, and to identify potential predictors of these endpoints. METHODS: This is a single-center retrospective cohort study of patients admitted from 2005 to 2010 with Crohn colitis, UC, or IBD-unspecified (IBD-U) and initiated on infliximab. RESULTS: We identified 29 patients (12 Crohn colitis, 15 UC, and 2 IBD-U; median age 14 years) with a median follow-up of 923 days. Eighteen patients (62%) required infliximab dose escalation (increased dose or decreased infusion interval). Infliximab failure occurred in 18 patients (62%) because of ineffectiveness in 12 (67%) and adverse reactions in 6 (33%). Twelve patients (41%) underwent colectomy. Subsequent need for infliximab dose escalation was associated with lower body mass index z score (P = 0.01), lower serum albumin (P = 0.03), and higher erythrocyte sedimentation rate (ESR) (P = 0.002) at baseline. ESR predicted subsequent infliximab dose escalation with an area under the curve of 0.89 (95% confidence interval [CI] 0.72-1.00) and a sensitivity and specificity at a cutoff of 38 mm/hour of 0.79 (95% CI 0.49-0.95) and 0.88 (95% CI 0.47-0.99), respectively. CONCLUSIONS: Most hospitalized pediatric patients with colitis treated with infliximab require early-dose escalation and fail the drug long term. Low body mass index and albumin and high ESR, may identify patients who would benefit from a higher infliximab starting dose.

MTG16 contributes to colonic epithelial integrity in experimental colitis.

OBJECTIVE: The myeloid translocation genes (MTGs) are transcriptional corepressors with both Mtg8(-/-) and Mtgr1(-/-) mice showing developmental and/or differentiation defects in the intestine. We sought to determine the role of MTG16 in intestinal integrity. METHODS: Baseline and stress induced colonic phenotypes were examined in Mtg16(-/-) mice. To unmask phenotypes, we treated Mtg16(-/-) mice with dextran sodium sulphate (DSS) or infected them with Citrobacter rodentium and the colons were examined for ulceration and for changes in proliferation, apoptosis and inflammation. RESULTS: Mtg16(-/-) mice have altered immune subsets, suggesting priming towards Th1 responses. Mtg16(-/-) mice developed increased weight loss, diarrhoea, mortality and histological colitis and there were increased innate (Gr1(+), F4/80(+), CD11c(+) and MHCII(+); CD11c(+)) and Th1 adaptive (CD4) immune cells in Mtg16(-/-) colons after DSS treatment. Additionally, there was increased apoptosis and a compensatory increased proliferation in Mtg16(-/-) colons. Compared with wild-type mice, Mtg16(-/-) mice exhibited increased colonic CD4;IFN-γ cells in vehicle-treated and DSS-treated mice. Adoptive transfer of wild-type marrow into Mtg16(-/-) recipients did not rescue the Mtg16(-/-) injury phenotype. Isolated colonic epithelial cells from DSS-treated Mtg16(-/-) mice exhibited increased KC (Cxcl1) mRNA expression when compared with wild-type mice. Mtg16(-/-) mice infected with C rodentium had more severe colitis and greater bacterial colonisation. Last, MTG16 mRNA levels were reduced in human ulcerative colitis versus normal colon tissues. CONCLUSIONS: These observations indicate that MTG16 is critical for colonocyte survival and regeneration in response to intestinal injury and provide evidence that this transcriptional corepressor regulates inflammatory recruitment in response to injury.

Surgically-relevant quality of life thresholds for the Short Inflammatory Bowel Disease Questionnaire in Crohn's disease.

BACKGROUND: Despite growing interest in patient-reported outcome measures to track the progression of Crohn's disease, frameworks to apply these questionnaires in the preoperative setting are lacking. Using the Short Inflammatory Bowel Disease Questionnaire (sIBDQ), this study aimed to describe the interpretable quality of life thresholds and examine potential associations with future bowel resection in Crohn's disease. METHODS: Adult patients with Crohn's disease completing an sIBDQ at a clinic visit between 2020 and 2022 were eligible. A stoplight framework was adopted for sIBDQ scores, including a "Resection Red" zone suggesting poor quality of life that may benefit from discussions about surgery as well as a "Nonoperative Green" zone. Thresholds were identified with both anchor- and distribution-based methods using receiver operating characteristic curve analysis and subgroup percentile scores, respectively. To quantify associations between sIBDQ scores and subsequent bowel resection, multivariable logistic regression models were fit with covariates of age, sex assigned at birth, body mass index, medications, disease pattern and location, resection history, and the Harvey Bradshaw Index. The incremental discriminatory value of the sIBDQ beyond clinical factors was assessed through the area under the receiver operating characteristics curve (AUC) with an internal validation through bootstrap resampling. RESULTS: Of the 2003 included patients, 102 underwent Crohn's-related bowel resection. The sIBDQ Nonoperative Green zone threshold ranged from 61 to 64 and the Resection Red zone from 36 to 38. When adjusting for clinical covariates, a worse sIBDQ score was associated with greater odds of subsequent 90-day bowel resection when considered as a 1-point (odds ratio [OR] [95% CI], 1.05 [1.03-1.07]) or 5-point change (OR [95% CI], 1.27 [1.14-1.41]). Inclusion of the sIBDQ modestly improved discriminative performance (AUC [95% CI], 0.85 [0.85-0.86]) relative to models that included only demographics (0.57 [0.57-0.58]) or demographics with clinical covariates (0.83 [0.83-0.84]). CONCLUSION: In the decision-making process for bowel resection, disease-specific patient-reported outcome measures may be useful to identify patients with Crohn's disease with poor quality of life and promote a shared understanding of personalized burden.

The Comorbidity of Patient-Reported Crohn's Disease Activity and Depression: The Role of Health Behavior Mediators.

Background: Longitudinal research reveals a unidirectional relationship between a nonsomatic symptom of depression, a negative view of the self, and later reported Crohn's disease (CD) activity. We evaluated whether health behaviors mediated this association using a longitudinal design. Methods: We studied 3304 adult volunteers with a self-reported diagnosis of CD who completed a baseline survey that included demographics, CD activity, a symptom-specific index of depression, and measures of physical activity, smoking, and sleep quality. Crohn's disease status and the cognitive index of depression were also measured 6 and 12 months after the baseline evaluation. We specified single-mediator and multiple-mediator models to elucidate the depression-disease activity relationship. Results: Among 2395 females and 909 males, we found a significant mediation effect for activity level (P < .001) after adjusting for age, sex, and body mass index. There was no evidence that sleep quality and smoking are significant single mediators. When we considered multiple mediation models, smoking and less activity partially mediate the depression-CD association. Conclusions: Smoking and lower levels of physical activity are potential mediators of the unidirectional association between a nonsomatic symptom of depression-a negative view of the self-and patient-reported CD activity. Evaluating and treating specific symptoms of depression may reduce the frequency of CD exacerbations.

Diagnosis of Inflammatory Bowel Disease-Associated Peripheral Arthritis: A Systematic Review.

BACKGROUND: Inflammatory bowel disease (IBD)-associated peripheral spondyloarthritis (pSpA) decreases quality of life and remains poorly understood. Given the prevalence of this condition and its negative impact, it is surprising that evidence-based disease definitions and diagnostic strategies are lacking. This systematic review summarizes available data to facilitate development and validation of diagnostics, patient-reported outcomes, and imaging indices specific to this condition. METHODS: A literature search was conducted. Consensus or classification criteria, case series, cross-sectional studies, cohort studies, and randomized controlled trials related to diagnosis were included. RESULTS: A total of 44 studies reporting data on approximately 1500 patients with pSpA were eligible for analysis. Data quality across studies was only graded as fair to good. Due to large heterogeneity, meta-analysis was not possible. The majority of studies incorporated patient-reported outcomes and a physical examination. A total of 13 studies proposed or validated screening tools, consensus, classification, or consensus criteria. A total of 28 studies assessed the role of laboratory tests, none of which were considered sufficiently accurate for use in diagnosis. A total of 17 studies assessed the role of imaging, with the available literature insufficient to fully endorse any imaging modality as a robust diagnostic tool. CONCLUSIONS: This review highlights existing inconsistency and lack of a clear diagnostic approach for IBD-associated pSpA. Given the absence of an evidence-based approach, a combination of existing criteria and physician assessment should be utilized. To address this issue comprehensively, our future efforts will be directed toward pursuit of a multidisciplinary approach aimed at standardizing evaluation and diagnosis of IBD-associated pSpA.

This systematic review highlights the lack of an evidence-based approach to the diagnosis of inflammatory bowel disease­associated peripheral spondyloarthritis and the need to standardize evaluation and diagnosis via multidisciplinary collaboration with development of patient-reported outcomes and imaging indices.