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Learn more: PMC Disclaimer | PMC Copyright Notice J Pediatr Gastroenterol Nutr . 2026 Jan 29;82(4):1029–1039. doi: 10.1002/jpn3.70365 Search in PMC Search in PubMed View in NLM Catalog Add to search Symptom cluster profiles in adolescents with inflammatory bowel disease: Cross‐sectional study using ImproveCareNow data Caeli Malloy Caeli Malloy 1 School of Nursing, University of Washington, Seattle, Washington, USA Find articles by Caeli Malloy 1, ✉ , Kurt Kroenke Kurt Kroenke 2 School of Medicine, Indiana University, Indianapolis, Indiana, USA 3 Regenstrief Institute, Indianapolis, Indiana, USA Find articles by Kurt Kroenke 2, 3 , Patrick O Monahan Patrick O Monahan 2 School of Medicine, Indiana University, Indianapolis, Indiana, USA Find articles by Patrick O Monahan 2 , Susan M Rawl Susan M Rawl 4 School of Nursing, Indiana University, Indianapolis, Indiana, USA Find articles by Susan M Rawl 4 , Steven J Steiner Steven J Steiner 2 School of Medicine, Indiana University, Indianapolis, Indiana, USA 5 Riley Children's Hospital, Indianapolis, Indiana, USA Find articles by Steven J Steiner 2, 5 , Wendy R Trueblood Miller Wendy R Trueblood Miller 4 School of Nursing, Indiana University, Indianapolis, Indiana, USA Find articles by Wendy R Trueblood Miller 4 ; for the ImproveCareNow Pediatric IBD Learning Health System Author information Article notes Copyright and License information 1 School of Nursing, University of Washington, Seattle, Washington, USA 2 School of Medicine, Indiana University, Indianapolis, Indiana, USA 3 Regenstrief Institute, Indianapolis, Indiana, USA 4 School of Nursing, Indiana University, Indianapolis, Indiana, USA 5 Riley Children's Hospital, Indianapolis, Indiana, USA * Correspondence Caeli Malloy, School of Nursing, University of Washington, 1959 NE Pacific St, Seattle, WA 98195, USA. Email: [email protected] ✉ Corresponding author. Revised 2026 Jan 7; Received 2025 Jun 22; Accepted 2026 Jan 9; Issue date 2026 Apr. © 2026 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. PMC Copyright notice PMCID: PMC13050818 NIHMSID: NIHMS2163658 PMID: 41609007 Abstract Objectives Sleep disturbance, pain, anxiety, depression, and fatigue are prevalent in adolescents and young adults with inflammatory bowel disease (IBD). These symptoms often present in co‐occurring sets, known as symptom clusters. We aimed to identify distinct symptom clusters and factors associated with symptom profiles in adolescents with IBD. Methods We recruited 105 adolescents with IBD seen at ImproveCareNow clinics. Data were collected from the ImproveCareNow clinical data registry (years since diagnosis, medications, and physician global assessment of disease activity) and an online survey (demographics, diagnosis, comorbidities, symptoms, self‐efficacy, self‐management, medication adherence, and sleep hygiene). Latent class analysis was used to classify adolescents into subgroups with distinct symptom profiles. Results Adolescents were 51.4% female, 83.8% white, a mean age of 14.9 years; 77.1% had Crohn's disease and 62.9% were on biologic therapy. Mean comorbidities were 0.6 and 70.5% had mild or quiescent disease activity. Three symptom profiles emerged: (1) Low Symptom Burden, characterized by a low probability of endorsing any symptoms; (2) High Symptom Burden, characterized by a high probability of endorsing sleep disturbance, pain, anxiety, depression, fatigue; and (3) Impaired Energy, characterized by a high probability of endorsing sleep disturbance and fatigue. Older age, more comorbidities, and lower IBD self‐efficacy were associated with the High Symptom Burden profile. Older age and lower IBD self‐efficacy were associated with the Impaired Energy profile. Conclusions Distinct symptom profiles highlight the unique symptom management needs of adolescents with IBD. Future research should explore biopsychosocial contributors and longitudinal trajectories of symptoms. Keywords: Crohn's disease, self‐management, ulcerative colitis What is Known Sleep‐wake disturbance, pain, anxiety, and low energy/fatigue (SPADE symptoms) represent frequent and burdensome symptoms in adolescents with inflammatory bowel disease (IBD). SPADE symptoms often appear as relatively stable groups of co‐occurring symptoms, known as symptom clusters; however, these symptom clusters have not been explored among adolescents with IBD. What is New Adolescents with IBD exhibited three distinct symptom cluster profiles: High Symptom Burden, Impaired Energy, and Low Symptom Burden. These profiles were characterized by high SPADE symptom burden, high sleep‐wake disturbance and fatigue burden, and low symptom burden, respectively. Results highlight the substantial and varied symptom experiences of adolescents with IBD. 1. INTRODUCTION Symptom burden in adolescents with inflammatory bowel disease (IBD) is substantial and has a detrimental impact on quality of life, 1 school absenteeism, 2 and social functioning. 1 Compared to healthy peers, adolescents with active IBD are more likely to report sleep‐wake disturbance, 3 pain, 4 and low energy/fatigue. 5 Pain 6 and fatigue 5 often persist in disease remission, indicating that symptom burden remains a significant, chronic, and undertreated problem. Collectively, s leep‐wake disturbance, p ain, a nxiety, d epression, and low e nergy/fatigue have been termed the SPADE pentad. 7 Besides being disruptive individually, the confluence of multiple SPADE symptoms together may have a greater impact on quality of life than any single SPADE symptom alone. SPADE symptoms often occur in unison, 8 , 9 in relatively stable groupings of co‐occurring symptoms known as symptom clusters. 10 Whereas gastrointestinal symptoms are understandably a predominant focus of IBD care, SPADE symptoms may go undetected. Identification of adolescent subgroups of distinct symptom cluster profiles has great potential to accelerate IBD symptom science as targeting multiple symptoms simultaneously can be more effective and have a greater impact on health outcomes than treating individual symptoms. 11 In this study, we aimed to identify profiles of SPADE symptom clusters in adolescents with IBD using latent class analysis. Additionally, we aimed to evaluate associations between symptom cluster profiles and demographic, clinical, and self‐management variables. 2. METHODS 2.1. Ethics statement The study was approved and deemed minimal risk by the Indiana University‐Purdue University Indianapolis Institutional Review Board. The study was also approved by the ImproveCareNow Research Committee. Informed parental consent and adolescent assent were obtained to participate in the study. 2.2. Design This study utilized a cross‐sectional design to examine relationships among SPADE symptoms and related factors in adolescents with IBD. 2.3. Sample Adolescents were eligible if they: (1) were 13–17 years of age, (2) had a formal diagnosis of IBD (ulcerative colitis or Crohn's disease), (3) could read and write English, (4) could independently complete online surveys, (5) were seen at an ImproveCareNow (ICN) clinic in the United States, and (6) had visited their IBD provider in the past 6 months. Standard formulas for power calculations do not exist for latent class analysis, but sample sizes of 100–300 participants are generally recommended. 12 In cases of well‐separated classes with fewer indicator variables, even smaller sample sizes are acceptable; in a well‐defined two‐class solution, a sample size as small as 30 could be considered adequate. 13 For a latent class analysis of five dichotomous variables, a sample size of 100 participants is reasonable for detecting two or three latent classes. 2.4. Recruitment Recruitment occurred through social media, mailings, and in clinic between October 2022 and December 2023. Figure 1 displays the study recruitment flow diagram. ICN, a collaborative care network connecting pediatric IBD providers, patients and families, was used as a primary resource for recruitment. Study information was shared in ICN‐affiliated clinics, on the ICN website, e‐newsletters, conferences, and social media, and posted in online IBD support groups. Participants were also recruited from a local ICN clinic, both in person and through direct patient mailings. Parents of potentially eligible adolescents were mailed information about the study. Research personnel screened adolescents for eligibility and obtained informed parental consent in person or via phone call. Figure 1. Open in a new tab STROBE flow diagram. Diagram showing four phases of participant recruitment. ICN, ImproveCareNow; STROBE, strengthening reporting of observational studies in epidemiology. To reduce participant burden to joining the study, an electronic screening and consent process was established. Parents interested in their adolescent participating in the study were asked to provide consent through an online REDCap survey. After implementing these electronic processes, there was a notable surge in screening survey responses, many of which were suspicious of bot activity. In response, several measures were implemented to screen suspected fraud, including installment of CAPTCHA, and survey time completion and IP address screening. All screening surveys were evaluated before participants were enrolled in the study and sent the online REDCap survey. 2.5. Data collection and measures Data were collected from: (1) a self‐administered REDCap survey assessing demographics, symptoms, and self‐management behaviors, and (2) the ICN clinical data registry. Demographic variables included self‐reported questions on age, sex, gender, race, and ethnicity. IBD diagnosis and comorbidities were assessed via self‐report. Adolescents were asked if they had ever been told by a healthcare provider that they had diabetes, breathing problems, heart condition/disease, high blood pressure, liver problems, cancer, or any other chronic condition. IBD self‐efficacy was assessed using the IBD Self‐Efficacy Scale for Adolescents and Young adults (IBDSES‐A) 14 ; higher scores indicate greater self‐efficacy for IBD self‐management. Self‐management skills were assessed using the Transition Readiness Assessment Questionnaire‐20 (TRAQ‐20). 15 The TRAQ‐20 assesses the degree to which adolescents with chronic conditions have mastered necessary skills for transitioning from pediatric to adult care, with higher scores indicating greater transition readiness. Medication adherence was assessed using the Medication Adherence Report Scale‐5 (MARS‐5) 16 ; higher scores indicated better adherence. Sleep hygiene was assessed using the Adolescent Sleep Hygiene Scale (ASHS) 17 ; higher scores indicate better sleep hygiene. SPADE symptoms were assessed using patient‐reported outcomes measurement information system (PROMIS) Pediatric Profile self‐report short forms: Sleep‐related impairment, Pain Interference, Emotional Distress‐Anxiety, Emotional Distress‐Depression, and Fatigue; 18 pain intensity was assessed using a 10‐point numeric rating scale. PROMIS instruments assess the presence, severity, and interference of symptoms over the past week, with higher scores indicating worse symptoms. In addition to its collaborative network, ICN maintains a comprehensive clinical data registry containing routinely collected clinical data at the time of diagnosis and at subsequent outpatient visits for patients seen at ICN centers. Years since diagnosis, current IBD medications, colostomy/ileostomy status, and physician global assessment (PGA) of disease activity were extracted from the registry. 2.6. Data management Survey data were exported from REDCap and uploaded into SPSS version 25. De‐identified data were extracted from the ICN registry and merged with surveys using unique participant identification numbers. Instruments were scored and T‐scores were calculated for PROMIS instruments using the PROMIS HealthMeasures Scoring Service. 19 (Table S1 reports internal consistency of survey instruments). Descriptive statistics were used to summarize clinical and demographic characteristics. Continuous variables are reported as mean ± standard deviation, and categorical variables are reported as frequencies and percentages. 2.7. Statistical analysis Symptoms were dichotomized as None/Mild or Moderate/Severe using established PROMIS cutoffs. 20 (Table S2 reports cutoff scores). Participants who reported 0/10 on the single‐item pain intensity scale were instructed to skip the pain interference measure and were thus categorized as “None” for pain interference. Latent class analysis was performed using Mplus version 8 to detect symptom cluster profiles. Missing data were handled by full information maximum likelihood estimation to reduce bias and optimize statistical power. Model fit was compared for one‐ to five‐class structures (Table S3 reports model fit information). The three‐class solution was chosen based on fit indices, parsimony, and interpretability. Symptom profile classes were labeled based on interpretation of results (Table S4 displays final class counts and proportions). Vermunt's three‐step approach 21 was implemented in Mplus to evaluate associations among symptom clusters and demographic, clinical, and self‐management variables in a multivariable multinomial logistic regression model with latent class membership as the outcome variable. To reduce the number of model covariates, bivariable analyses were initially conducted. Covariates with bivariable p < 0.20 for any of the three pairwise between‐class comparisons were included in the initial pool of variables for a manually‐implemented backward selection to remove nonsignificant variables from the model. Variables tested for bivariable associations but were not significant at p < 0.20 included biologics use, corticosteroid use, hydrocortisone enema/suppository use, transition readiness, and years since diagnosis. The following variables were significant at p < 0.20 and were therefore included in the initial variable pool for the backwards selection model: age, sex, IBD diagnosis, number of comorbidities, aminosalicylate use, immunomodulator use, nonbiologic IBD medication use, additional IBD medication use, disease activity, sleep hygiene, and IBD self‐efficacy. Because the Mplus procedure does not provide an omnibus test for comparing all three classes, and because Classes 1 and 3 were the largest classes garnering the highest power, a two‐step backward removal rule was used: (1) the p ‐value for comparing Classes 1 and 3 was used as the criterion for manual backward removal steps (i.e., variable with highest p ‐value removed at each step), and (2) variables were not removed (regardless of p ‐value for Class 1 vs. Class 3) if at least one of the class comparisons (Class 1 vs. 3; Class 2 vs. 3; Class 1 vs. 2) was significant at p < 0.05. 3. RESULTS 3.1. Sample characteristics One hundred and thirteen adolescents were invited to take the survey. Surveys with less than 80% completion were excluded from analysis, resulting in 105 completed surveys. Table 1 presents sample clinical and demographic characteristics. Table 1. Demographic and clinical characteristics of participants. Total sample size: N = 105 Characteristic Response n (%) Sex Female 54 (51.4) Male 50 (47.6) Missing 1 (1.0) Gender Cisgender 99 (94.3) Non‐binary or gender non‐conforming 2 (1.9) Agender 1 (1.0) Questioning or unsure 1 (1.0) Missing 2 (1.9) Race White 88 (83.8) Black 9 (8.6) Asian 5 (4.8) American Indian/Alaska Native 1 (1.0) Multiracial 1 (1.0) Missing 1 (1.0) Ethnicity Hispanic 3 (2.9) Non‐Hispanic 101 (96.2) Missing 1 (1.0) IBD diagnosis Crohn's disease 81 (77.1) Ulcerative colitis 23 (21.9) Both 1 (1.0) ICN center Local ICN center 47 (44.8) National ICN center 58 (55.2) Physician global assessment of disease activity Quiescent 64 (61.0) Mild 10 (9.5) Moderate 6 (5.7) Severe 1 (1.0) Missing 24 (22.9) Taking aminosalicylate Yes 9 (8.6) No 72 (68.6) Missing 24 (22.9) Taking antibiotic Yes 1 (1.0) No 24 (22.9) Missing 80 (76.2) Taking corticosteroid Yes 10 (9.5) No 71 (67.6) Missing 24 (22.9) Taking hydrocortisone enema/suppository Yes 4 (3.8) No 74 (70.5) Missing 27 (25.7) Taking immunomodulator Yes 10 (9.5) No 71 (67.6) Missing 24 (22.9) Taking biologic Yes 66 (62.9) No 15 (14.3) Missing 24 (22.9) Taking other immunosuppressant Yes 0 (0) No 24 (22.9) Missing 81 (77.1) Taking non‐biologic IBD medication Yes 27 (25.7) No 47 (44.8) Missing 31 (29.5) Taking additional IBD medications Yes 11 (10.5) No 60 (57.1) Missing 34 (32.9) Colectomy Yes 0 (0) No 76 (72.4) Missing 29 (27.6) Ileostomy/colostomy Yes 1 (1.0) No 77 (73.3) Missing 27 (25.7) Characteristic Total N Valid n Missing n Mean (SD) Range Age 105 105 0 14.93 (1.47) 13–17 Number of comorbidities 105 104 1 0.59 (1.06) 0–7 Years since diagnosis 105 89 16 3.58 (3.21) 0–14 Open in a new tab Note : Table depicting demographic and clinical characteristics of the sample. Abbreviations: IBD, inflammatory bowel disease; ICN, Improve Care Now; SD, standard deviation. The sample was 51.4% female. Mean age was 14.9 ± 1.5 years. Most participants were cisgender (94.3%), white (83.8%), non‐Hispanic (96.2%), and had Crohn's disease (77.1%). Nearly half (44.8%) of participants were recruited from a local ICN center, with the other half (55.2%) seen at 26 ICN centers across the country. Most participants ( n = 66; 62.9%) were receiving biologic treatment, with only 10 (9.5%) participants receiving corticosteroids. Total number of comorbidities ranged from 0 to 7, with participants reporting a mean of 0.6 ± 1.1 comorbidities. The most frequently reported comorbidities were respiratory conditions (18.1%), liver conditions (2.9%), eosinophilic esophagitis (2.9%), and iron deficiency (2.9%). Time since diagnosis with IBD was mean of 3.6 ± 3.2 years at time of survey completion; 13 participants were newly diagnosed (<1 year). Most participants ( n = 74; 70.4%) had quiescent or mild disease activity. Participants reported slightly worse sleep‐wake disturbance compared to the population mean, and average (relative to the U.S. general population) levels of pain interference, anxiety, depression, and fatigue. The most prevalent SPADE symptoms that were moderate to severe were sleep‐wake disturbance and depression ( n = 41; 39%), followed by anxiety ( n = 38; 36%), fatigue ( n = 36; 34%), and pain interference ( n = 26; 25%). We used independent t ‐tests to test differences in SPADE symptom severity between participants seen at the local ICN center compared to those recruited from other ICN centers. We did not find significant differences in SPADE symptom severity between the two groups (all p > 0.05). Most participants ( n = 61; 58%) were not currently taking oral IBD medications. Among participants taking oral medication ( n = 44), mean medication adherence was adequate (21.0 ± 3.9). Overall, participants reported moderate levels of self‐management skills/transition readiness (3.4 ± 0.8), IBD self‐efficacy (50.3 ± 5.8), and sleep hygiene behaviors (4.4 ± 0.6). Table S5 presents symptom and self‐management scores. Table S6 presents symptom severity distribution. 3.2. Symptom clusters Participants were classified into three profiles or classes of symptom clusters. Class 1, composing approximately 27% of the sample, was labeled “High Symptom Burden” as participants classified in this group had a high probability of endorsing each SPADE symptom. Class 2, composing about 11% of the sample, was labeled “Impaired Energy” as participants were characterized by a high probability of endorsing fatigue and sleep‐wake disturbance. Class 3, composing about 62% of the sample, was labeled “Low Symptom Burden” as participants classified in this group had a low probability of endorsing any of the SPADE symptoms. See Figure 2 for probabilities of endorsing each SPADE symptom by assigned symptom class. Figure 2. Open in a new tab Bar chart: Probability of endorsing each symptom by assigned symptom cluster profile. Bar chart depicting probabilities of endorsing each SPADE symptom by assigned symptom cluster class: Low symptom burden, high symptom burden, and impaired energy. SPADE, Sleep‐wake disturbance, pain, anxiety, and low energy/fatigue. 3.3. Factors associated with symptom cluster profiles Age, number of comorbidities, and IBD self‐efficacy scores were significantly associated with latent class membership (Table 2 ). Odds of being classified into the Impaired Energy profile compared to Low Symptom Burden increased by 75% for each additional year in age and shrank by 11% for each unit increase in IBD self‐efficacy. Odds of being classified into the High Symptom Burden profile compared to Low Symptom Burden increased by 76% for each additional year in age and shrank by 21% for each unit increase in IBD self‐efficacy. Odds of being classified into the High Symptom Burden profile compared to Low Symptom Burden were 2.46 times higher for each additional comorbidity reported. Odds of being classified into the High Symptom Burden profile compared to Impaired Energy increased nearly ninefold for each additional comorbidity reported. Table 2. Variables associated with symptom profile class membership. Class 1 High Symptom Burden compared to Class 3 Low Symptom Burden Class 2 Impaired Energy compared to Class 3 Low Symptom Burden Class 1 High Symptom Burden compared to Class 2 Impaired Energy OR 95% CI OR 95% CI OR 95% CI Age 1.76 1.11, 2.81 1.75 1.02, 3.01 1.01 0.54, 1.88 Number of comorbidities 2.46 1.34, 4.50 0.28 0.05, 1.58 8.81 1.52, 51.11 IBD self‐efficacy 0.79 0.68, 0.92 0.89 0.80, 0.99 0.90 0.78, 1.03 Open in a new tab Note : Bolded values indicate p ‐value < 0.05. Table depicting odds ratios and confidence intervals of variables associated with symptom profile class with significant variables bolded. Abbreviations: CI, confidence interval; IBD, inflammatory bowel disease; OR, odds ratio. 4. DISCUSSION Our study underscores the substantial burden of SPADE symptoms experienced by adolescents with IBD, particularly impaired energy symptoms: sleep disturbance and fatigue. It is unsurprising that fatigue and sleep problems are challenges for adolescents with IBD. In the general population, up to 69% of adolescents receive insufficient sleep 22 and report daytime sleepiness. 23 Disease activity can also impact sleep. Adolescents with active IBD can experience nocturnal symptoms leading to more sleep awakenings, 24 and are more likely to experience poor sleep quality, 25 depression, 25 pain, 25 and fatigue. 26 Sleep can also impact symptoms; greater difficulty falling asleep predicts next‐day pain in children with Crohn's disease. 27 Age, number of comorbidities, and IBD self‐efficacy were significantly associated with symptom profiles. Some studies have found that older adolescents with IBD report worse health‐related quality of life 28 , 29 and depressive symptoms 30 compared to younger adolescents. This disparity could be explained by changes in overall quality of life driven by changing psychosocial development and autonomy needs, as well as higher rates of psychological comorbidity. Additionally, presence of multiple comorbidities may exacerbate symptoms. 31 Finally, it is possible that those with higher IBD self‐efficacy can better manage their condition, or that those with lower symptom burden experience fewer challenges with self‐management and consequently report greater self‐efficacy. IBD self‐efficacy is crucial for transitioning adolescents to adult care and is positively associated with disease‐related knowledge 32 and transition readiness. 33 In our study, disease activity and pharmacologic treatments were not significant predictors of symptom profiles. While some SPADE symptoms are positively associated with disease activity, symptoms including pain 6 and fatigue 5 also are highly prevalent in remission. Treatment factors may also affect SPADE symptoms. Corticosteroid treatment is effective in inducing disease remission, thereby decreasing pain and gastrointestinal symptoms. 34 Adverse effects, however, (e.g., insomnia, anxiety, and mood disorders) are well‐documented and may worsen SPADE symptoms. 35 Given sample characteristics, it is possible that low variability in disease activity and treatment precluded detection of significant relationships between disease activity, treatment, and symptom profiles. Nevertheless, the lack of relationship between SPADE symptom profiles and disease activity in our sample aligns with literature suggesting complex relationships between SPADE symptoms and disease activity. Psychological factors (e.g., pain catastrophizing, coping, and psychological comorbidities), 36 alterations in the gut–brain axis (e.g., visceral hypersensitivity), 37 and health behaviors (e.g., poor nutrition, physical inactivity) 26 can contribute to SPADE symptom burden in adolescents with IBD. Comorbid gastrointestinal conditions such as Celiac's disease 38 and functional abdominal pain 39 also can contribute to symptom burden. Results should be interpreted in the context of limitations. Most participants had Crohn's disease, were not newly diagnosed, received biologic therapy, and were in remission. Although adequate for preliminary analyses, the sample size was relatively small for conducting latent class analysis. While some significant associations between demographic/psychosocial factors and symptom profiles were identified, it is likely that additional associations could be detected with a larger sample size. We assessed oral medication adherence, but most participants were receiving biologic treatment (administered by injection or infusion). For participants receiving infusions, non‐adherence is generally minimized by maintaining a fixed schedule. However, adherence may be lower among those administering injections at home, which was not captured by the adherence measure we used. As a cross‐sectional study, conclusions about causal relationships between symptoms and associated factors cannot be drawn. Bowel symptoms were not specifically measured, though these are often considered in clinical assessment of disease activity. Additional limitations involve the lack of objective measures of sleep patterns, medication adherence, and endoscopic disease activity. While patient self‐report of IBD diagnosis has shown to be consistent with physician report, 40 relying on self‐report rather than documented diagnosis could be considered another limitation. Additionally, some factors that may influence symptoms were not assessed, including the use of sleep medications, prior psychiatric treatment, and nutrition. Nevertheless, this study had several notable strengths. This study is the first to examine symptom clusters among all five SPADE symptoms in adolescents with IBD. Using latent class analysis, we described three distinct symptom profiles of SPADE symptoms in our sample. Validated cutoffs were used to dichotomize SPADE symptom severity. Participants represented a national sample and were recruited from clinics and social media. Additionally, participants were somewhat (but not greatly) diverse in terms of race, gender, and ethnicity. Finally, our study incorporated both clinical data extracted from a national database and validated self‐report measures. At present, symptom management interventions targeting simultaneous symptoms for adolescents with IBD are lacking. Clinicians should assess SPADE symptoms and potential clustering symptoms, even in remission. Single‐item numeric rating scales are an ultra‐brief option for SPADE screening. 41 Adolescents reporting high symptom burden across all five SPADE symptoms could be experiencing active disease; however, our results suggest other factors may contribute to symptom burden. Given the complex potential contributing biopsychosocial factors, SPADE symptoms should be interpreted with caution as they are not necessarily as a sign of treatment failure. If necessary, patients should be referred to appropriate specialists, for example, psychiatry or sleep medicine providers. Several interventions targeting multiple co‐occurring symptoms have been tested in patients with other chronic conditions and may also benefit those with IBD. For instance, cognitive behavioral therapy (CBT) has been shown to be effective for improving pain, fatigue, and sleep‐wake disturbance in patients with cancer. 42 Additionally, exercise, mindfulness‐based strategies and other treatments may benefit multiple symptoms including SPADE. 43 Future studies should investigate symptom cluster etiology and develop and test interventions tailored to adolescent needs. Symptom management interventions should target the specific symptom cluster experienced by the adolescent. Moreover, future studies should include participants with more active disease to explore relationships among disease activity, treatment, and symptom clusters. Longitudinal work is needed to understand how symptoms cluster and evolve over time, as well as the factors associated with changes in symptom burden. Also, more studies evaluating access to and effectiveness of behavioral interventions are warranted. 5. CONCLUSION Adolescents with IBD reported numerous, co‐occurring burdensome symptoms that impacted quality of life and functioning. To our knowledge, our study represents the first to examine SPADE symptom cluster profiles in adolescents with IBD. Fatigue and sleep‐wake disturbance emerged as prominent features of both major symptom profiles identified in this study, underscoring a need for symptom management interventions. Older adolescents with multiple comorbidities and exhibiting low IBD self‐efficacy may especially benefit from tailored symptom management interventions. Results lay the groundwork for future longitudinal and experimental research aimed at supporting self‐management and quality of life. CONFLICT OF INTEREST STATEMENT The authors declare no conflicts of interest. Supporting information Supplementary Table S1. Internal Consistency of Survey Instruments . Supplementary Table S1 caption: Note . IBD= inflammatory bowel disease; PROMIS= Patient‐Reported Outcomes Measurement Information System; SF= short form. Alt text: Table depicting number of responses, number of items, and Cronbach's alpha for each survey instrument. JPN3-82-1029-s006.docx (21KB, docx) Supplementary Table S2. SPADE Symptom Cutoff Scores . Supplementary Table S2 caption: Note . PROMIS= Patient‐Reported Outcomes Measurement Information System; SF= short form; SPADE=Sleep‐Wake Disturbance, Pain, Anxiety, Depression, and Low Energy/Fatigue. Alt text: Table depicting SPADE symptom cutoff scores for None, Mild, Moderate, and Severe categories for each PROMIS short form instrument. JPN3-82-1029-s003.docx (20.5KB, docx) Supplementary Table S3. Latent Class Model Selection . Supplementary Table S3 caption: Note . AIC= Akaike Information Criterion; BIC= Bayesian Information Criterion; LMR= Lo‐Mendell‐Rubin; LRT= Likelihood Ratio Test; VLMR= Vuong‐Lo‐Mendell‐Rubin. Alt text: Table depicting model fit criteria, likelihood ratio tests, and entropy for models comparing one to five latent classes. JPN3-82-1029-s001.docx (21.2KB, docx) Supplementary Table S4. Final Class Counts and Proportions . Supplementary Table S4 caption : Note . Participants were classified into the three classes for remaining analyses using the “most likely class membership” which is the most commonly recommended procedure in latent class analysis. Alt text: Table depicting final class counts and proportions for each symptom cluster profile based on estimated model and based on most likely class membership. JPN3-82-1029-s005.docx (20.1KB, docx) Supplementary Table S5. SPADE Symptom and Self‐Management Scores . Supplementary Table S5 caption : Note . IBD= inflammatory bowel disease; PROMIS= Patient‐Reported Outcomes Measurement Information System; SD= standard deviation; SF= short form; SPADE= Sleep‐Wake Disturbance, Pain, Anxiety, Depression, and Low Energy/Fatigue. Alt text: Table depicting SPADE symptoms and self‐management scores of the sample. JPN3-82-1029-s002.docx (21.9KB, docx) Supplementary Table S6. SPADE Symptom Severity Distribution . Supplementary Table S6 caption: Note . SPADE= Sleep‐Wake Disturbance, Pain, Anxiety, Depression, and Low Energy/Fatigue. * Except for sleep, cut points for mild, moderate and severe symptoms were Patient‐Reported Outcomes Measurement Information System (PROMIS) scores of 50, 55, and 65. Cut points for Sleep were 55, 59 and 65. Alt text: Table depicting severity distribution of SPADE symptoms in sample in None, Mild, Moderate, and Severe categories. JPN3-82-1029-s004.docx (20.7KB, docx) ACKNOWLEDGMENTS We acknowledge the participation of the Regenstrief Institute. We would like to express sincere gratitude to all the children, families, clinicians and staff at the centers participating in the ImproveCareNow (ICN) Pediatric IBD Learning Health System. A full list of participating centers is available at: https://www.improvecarenow.org/care-center . This work was supported by the National Institute of Nursing Research of the National Institutes of Health (T32NR018407 and T32NR016913 to Caeli Malloy) and the Midwest Nursing Research Society through the Joseph & Jean Buckwalter Dissertation Grant (Caeli Malloy). This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Thank you to the providers, adolescents, and families who supported this study. We would like to offer heartfelt appreciation to the providers and staff at the following clinics: Arkansas Children's Hospital, Cardinal Glennon Children's Medical Center, St. Louis University, Children's Healthcare of Atlanta, Children's Hospital of Alabama, Children's Hospital of The King's Daughters, Children's National Health System, Children's Mercy, Cincinnati Children's Hospital Medical Center, Cleveland Clinic Children's, Dayton Children's Hospital, Dell Children's Medical Center of Central Texas, Geisenger Janet Weis Children's Hospital, Helen DeVos Children's Hospital, Kravis Children's Hospital at Mount Sinai, Levine Children's Hospital, Medical University of South Carolina Children's, Nationwide Children's Hospital, Nemours Children's Health, Oklahoma University Medical Center, Pediatric Gastroenterology & Nutrition Associates, Pediatric Specialists of Virginia, Phoenix Children's Hospital, Rady Children's Hospital San Diego, Rainbow Babies & Children's Hospital, Riley Hospital for Children, Seattle Children's Hospital, St. Louis Children's Hospital‐ Washington University, Stanford Children's Health, University of California, San Francisco Benioff Children's Hospitals, University of Iowa Stead Family Children's Hospital, University of North Carolina at Chapel Hill, UPMC Children's Hospital of Pittsburgh, and Yale New Haven Children's Hospital. 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Alt text: Table depicting number of responses, number of items, and Cronbach's alpha for each survey instrument. JPN3-82-1029-s006.docx (21KB, docx) Supplementary Table S2. SPADE Symptom Cutoff Scores . Supplementary Table S2 caption: Note . PROMIS= Patient‐Reported Outcomes Measurement Information System; SF= short form; SPADE=Sleep‐Wake Disturbance, Pain, Anxiety, Depression, and Low Energy/Fatigue. Alt text: Table depicting SPADE symptom cutoff scores for None, Mild, Moderate, and Severe categories for each PROMIS short form instrument. JPN3-82-1029-s003.docx (20.5KB, docx) Supplementary Table S3. Latent Class Model Selection . Supplementary Table S3 caption: Note . AIC= Akaike Information Criterion; BIC= Bayesian Information Criterion; LMR= Lo‐Mendell‐Rubin; LRT= Likelihood Ratio Test; VLMR= Vuong‐Lo‐Mendell‐Rubin. Alt text: Table depicting model fit criteria, likelihood ratio tests, and entropy for models comparing one to five latent classes. JPN3-82-1029-s001.docx (21.2KB, docx) Supplementary Table S4. Final Class Counts and Proportions . Supplementary Table S4 caption : Note . Participants were classified into the three classes for remaining analyses using the “most likely class membership” which is the most commonly recommended procedure in latent class analysis. Alt text: Table depicting final class counts and proportions for each symptom cluster profile based on estimated model and based on most likely class membership. JPN3-82-1029-s005.docx (20.1KB, docx) Supplementary Table S5. SPADE Symptom and Self‐Management Scores . Supplementary Table S5 caption : Note . IBD= inflammatory bowel disease; PROMIS= Patient‐Reported Outcomes Measurement Information System; SD= standard deviation; SF= short form; SPADE= Sleep‐Wake Disturbance, Pain, Anxiety, Depression, and Low Energy/Fatigue. Alt text: Table depicting SPADE symptoms and self‐management scores of the sample. JPN3-82-1029-s002.docx (21.9KB, docx) Supplementary Table S6. SPADE Symptom Severity Distribution . Supplementary Table S6 caption: Note . SPADE= Sleep‐Wake Disturbance, Pain, Anxiety, Depression, and Low Energy/Fatigue. * Except for sleep, cut points for mild, moderate and severe symptoms were Patient‐Reported Outcomes Measurement Information System (PROMIS) scores of 50, 55, and 65. Cut points for Sleep were 55, 59 and 65. Alt text: Table depicting severity distribution of SPADE symptoms in sample in None, Mild, Moderate, and Severe categories. 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