BACKGROUND CONTEXT:Mechanical chronic low back pain (CLBP) associated with lumbar multifidus muscle dysfunction is a major cause of long-term disability. Available nonoperative and interventional treatments often provide limited and transient benefit. Restorative neurostimulation is intended to activate the lumbar multifidus to restore neuromuscular control and address the underlying pathophysiology of mechanical CLBP. PURPOSE:The purpose of this extension of the original randomized controlled trial was to track outcomes in a crossover group for the subsequent treatment year. Participants in the original treatment group were also followed for an additional year, allowing long-term clinical follow-up. STUDY DESIGN/SETTING:RESTORE is a postmarket, multicenter, open-label randomized controlled trial performed at 25 clinical sites in the United States. PATIENT SAMPLE:A total of 203 participants were randomized 1:1 to restorative neurostimulation or optimal medical management. At the completion of the randomized phase, 80/96 (83%) eligible control participants elected to cross over to restorative neurostimulation treatment. These participants and the original treatment group were followed for an additional year. OUTCOME MEASURES:Oswestry Disability Index (ODI), back pain (Numerical Rating Scale [NRS]), and health-related quality of life (EuroQol 5-Dimension 5-Level [EQ-5D-5L]) were assessed at 18 and 24 months postrandomization. Outcomes included responder rates based on minimal clinically important change thresholds, pain remission, composite responder definitions, work ability, subject global impression of change, opioid use, and number needed to treat. METHODS:This prespecified delayed-start crossover analysis included a nonrandomized comparison of outcomes between early and delayed-start treatment groups, with within-group analyses serving as the primary basis for inference regarding crossover efficacy. Longitudinal outcomes for the treatment group were analyzed using mixed models for repeated measures. Crossover group outcomes were analyzed using completer analyses. RESULTS:The treatment group improvements were sustained through 24 months, with mean changes from baseline of -24.6±17.1 in ODI, -4.2±2.4 in NRS, and +0.189±0.163 in EQ-5D-5L (all p<.001). After crossover, participants demonstrated significant improvements after 1 year of active therapy, with mean changes from baseline of -21.1±14.8 in ODI, -3.8±2.2 in NRS, and +0.191±0.144 in EQ-5D-5L (all p<.001), comparable in magnitude to those observed in the treatment group at the same timepoint. At 12 months, responder rates in the treatment group were 70% for ODI ≥15 point improvement, 53% for ≥50% NRS reduction, 52% for NRS remission, and 72% for the composite endpoint, compared with 17%, 6%, 6%, and 12% in the control group, respectively; after crossover, corresponding responder rates at 12 months of active therapy were 64%, 61%, 60%, and 73%, consistent in magnitude with those observed in the treatment group at the equivalent timepoint of therapy. Corresponding numbers needed to treat ranged from 1.7 to 2.2 and remained similarly low when the crossover outcomes were compared with control. CONCLUSIONS:These findings reinforce the role of restorative neurostimulation as an effective therapeutic option for patients with multifidus dysfunction-related CLBP who have exhausted conservative care and suggest that earlier intervention may reduce prolonged disability and loss of quality of life.

BACKGROUND:This study aimed to develop predictive models for acute severe ulcerative colitis (ASUC) using data from East Asian (EA) patients and to validate their performance in an Australia/New Zealand (ANZ) cohort. METHODS:A retrospective international study was conducted across 23 referral hospitals in EA and ANZ, enrolling consecutive ASUC patients between January 2015 and December 2022. Logistic regression analyses were used to construct predictive models for 1-year colectomy and non-response to corticosteroid therapy (NRS). RESULTS:Overall, 826 patients with ASUC were included (411 EA and 415 ANZ). Among EA patients, independent predictors of 1-year colectomy included female sex, prior exposure to tumor necrosis factor inhibitors, and admission albumin ≤3 g/dL. Independent predictors of NRS in the EA cohort were age at diagnosis  ≤37 years, baseline steroid use, admission albumin ≤2.5 g/dL, and the presence of extraintestinal manifestations. The EA-derived scoring systems demonstrated strong predictive performance within the EA cohort (1-year colectomy: P < .0001; NRS: P = .001) but showed limited utility in the ANZ cohort (P = .106 and P = .012). In contrast, European-developed models-including the French 1-year colectomy score and the ADMIT-ASC index for NRS-accurately predicted outcomes in the ANZ cohort (P = .007 and P < .0001) but had reduced predictive capacity in the EA cohort (P = .106 and P = .026). These findings were consistent in both cohorts following propensity score matching. CONCLUSIONS:Predictive factors for ASUC differ substantially between EA and ANZ patients, highlighting the need for population-specific predictive tools.

BACKGROUND:Despite high rates of psychological comorbidity, research indicates low uptake of mental health services in inflammatory bowel disease (IBD) cohorts. With little known about factors influencing help-seeking in IBD, this review summarised existing knowledge regarding barriers and facilitators to formal mental health help-seeking in IBD. METHODS:Systematic search of six databases (PubMed, Scopus, Web of Science Core Collection, Medline, PsycINFO and CINAHL) was conducted in March 2026. Narrative synthesis was undertaken to summarise inferential and non-inferential findings across key help-seeking research domains: orientation, intention, actual engagement. RESULTS:Nineteen studies (N = 6285, Mage = 38.03, 58% female, 59% Crohn's disease) were identified, with studies assessed to have overall moderate quality (measured using the Mixed Methods Appraisal Tool [MMAT]). Rates of engagement ranged from 21%-64% (weighted average: 37.15%). Eighty factors were explored across included studies, with only psychosocial factors (health-related quality of life, IBD-related concerns, anxiety, depression) consistently and positively associated with help-seeking domains. Barriers spanned several categories: sociodemographics (e.g., busy lifestyles); clinical characteristics (e.g., disease duration); psychosocial factors (e.g., low perceived need); structural and systemic factors (e.g., cost, lack of IBD-specific therapists); treatment-related factors (e.g., stigma). CONCLUSIONS:Barriers to formal mental health help-seeking may be more extensive and varied than factors facilitating help-seeking in IBD, indicating a wide range of potential intervention targets. Findings, however, highlight significant methodological limitations and a fragmented and underdeveloped evidence base, with recommendations provided to address past limitations and guide future research.

BACKGROUND:Thiopurines remain key immunomodulators for inflammatory bowel disease (IBD) but require close safety monitoring for adverse effects. AIMS:We evaluated a virtual multidisciplinary team (MDT) thiopurine monitoring service and compared it to standard care and a pharmacy-led monitoring service. METHODS:We conducted a retrospective cohort study at an Australian tertiary health service, comparing IBD patients initiated on thiopurines across three study periods: (i) prior to any thiopurine monitoring service; (ii) pharmacy-led thiopurine monitoring service; and (iii) virtual MDT thiopurine monitoring service. The MDT model involved telehealth case reviews by IBD clinicians, pharmacists and nurse consultants. Outcomes included frequency of early clinical reviews, thiopurine methyltransferase (TPMT) phenotype screening, dose optimisation, adverse effects, medication persistence and the promotion of IBD preventive care. RESULTS:A total of 285 patients were included. TPMT phenotype assessment improved across periods (80.3%, 92.5%, 95.6%; P = 0.007). Dose optimisation by 4 months was similar across cohorts (28.8%, 40.2%, 37.8%; P = 0.107). Adverse effect rates, including myelosuppression (4.9%), were comparable. Thiopurine persistence during the MDT monitoring service decreased, potentially due to increased de-escalation of combination therapy to biologic monotherapy. Promotion of cervical screening, skin checks and vaccination improved with the MDT monitoring service. Monitoring services improved the proportion of clinical reviews within 2 weeks of thiopurine initiation, although increased the total number of reviews in the first 3 months. CONCLUSION:A virtual multidisciplinary thiopurine monitoring service supported more timely clinical review, pharmacogenomic screening and systematic promotion of IBD preventive care. Adverse effect rates were similar across monitoring models. The MDT monitoring model may also facilitate recognition of patients suitable for treatment de-escalation. These findings highlight the potential of structured monitoring approaches to support safe and proactive thiopurine use in IBD, though further research is needed to assess long-term outcomes and sustainability.

There is increasing interest in using ≥2 advanced therapies in inflammatory bowel disease (IBD) for refractory disease, multi-organ involvement and concurrent autoimmune conditions. However, data on prescribing practices are extremely limited, and comparative efficacy and safety remain largely unknown. Prior meta-analyses have included <280 patients, primarily from small case series with heterogeneous reporting and mostly without objective outcomes [1]. We collected a comprehensive binational registry (Australia & Taiwan) of patients with IBD on combined advanced therapies (ATs)/combined immunosuppressive therapies outside of regular prescribing practice used in overlap ≥1 month. There were 307 combinations in 257 patients, median age 37 years, 146/257 (56.8%) Crohn’s disease (CD) & 110/257 (42.8%) ulcerative colitis, 111/257 (43.2%) female primarily from Australia (220/257, 85.6%; Taiwan 37/257, 14.4%). Commonest combinations were: Vedolizumab (VED) + Janus kinase inhibitor (JAK) (n = 57, 18.6%), JAK + ustekinumab (UST) (n = 52, 16.9%) & VED + tumour necrosis factor inhibitor (TNFi) (n = 44, 14.3%). Overall, via 5-point Likert scale, the combinations were deemed effective by the clinician in 66.8%. p19 inhibitors (p19i) + JAK, UST + JAK, UST + TNF had the greatest clinician-deemed efficacy rates (effective ≥70%) whereas UST + tacrolimus (TAC), JAK + TAC, & TNFi + JAK were deemed the poorest (<60%) (P=0.032). Clinical remission was achieved in 174/307 (56.7%). In 198/307 (65%), there was confirmed objective improvement (biochemically, endoscopically, and/or radiologically). The commonest adverse events (AEs) were from uncontrolled disease (n = 17, 5.5%), though there were 5/307 (1.6%) serious infections & 11/307 (3.6%) opportunistic infections. Two combinations were associated with life-threatening AEs (Common Terminology Criteria for Adverse Events (CTCAE): 4), both associated with uncontrolled IBD activity. The commonest serious AE (CTCAE 3) was from uncontrolled IBD activity (4/307, 1.3%). There were three deaths, two from uncontrolled IBD activity, one from myeloma progression in a patient with liver cirrhosis. AEs were more frequent in combinations containing JAK & tacrolimus (21/87 (24.1%) & 17/63 (27.0%) respectively, & least frequent with Th17 inhibition (p19i & UST, 16/118 (13.6%), P = 0.03). This comprehensive binational registry of combined advanced therapies in IBD, the largest to date, shows that combination use in treatment-resistant IBD is effective in the majority with acceptable safety. However, despite combination of agents, medication inefficacy remains a key area of concern. We demonstrate signals for greater efficacy & safety using several combinations that require further investigation. References: [1]Alayo QA, et al. Systematic Review With Meta-analysis: Safety and Effectiveness of Combining Biologics and Small Molecules in Inflammatory Bowel Disease. Crohns Colitis 360. 2022 Feb 10;4(1):otac002. Conflict of interest: Dr. Chetwood, John: JDC has received speaker fees from Novartis, Takeda, Johnson & Johnson, and Eli Lilly. Le, Puo-Hsien: No conflict of interest Wei, Shu Chen: Consultancy fees: AbbVie, Bristol Myers Squibb, Cornerstones, Ferring Pharmaceuticals Inc., Janssen/J & ampJ, Pfizer, Sanofi, SPYRE, Takeda, ThermoFisher. Lectures and/or speakers’ bureau payments: AbbVie, Bristol Myers Squibb, Celltrion, CornerStones, Excelisior, Ferring Pharmaceuticals Inc., Janssen/J & ampJ, Pfizer, Takeda, ThermoFisher. Wu, Hsin-Yun: No conflict of interest Corte, Crispin: Grants: Ferring, GESA Consulting: Abbvie, Ferring, Celltrion, Chiesi, Janssen, Takeda. Support for travel for meetings to support study: Pfizer, Takeda, Celltrion, Chiesi, Ferring, Falk. Lightowler, Daniel: Speaker Fees: Pfizer, DrFalk, Eli Lily Advisory Board: AbbVie, Eli Lily, Menarini, Janssen, AGPAL Travel: Pfizer, Celgene, Allergen, Janssen, AbbVie Research Support: Janssen, Ferring Education: DrFalk, AbbVie, Janssen, Pfizer Gilmore, Robert: Grant support from the Gastroenterological Society of Australia (GESA) and speaker honoraria from Johnson and Johnson, Pfizer, and education or conference support from Pfizer Chin, Simone: No conflict of interest Garg, Mayur: No conflict of interest Bahmani Kashkooli, Soleiman: Research grants from AbbVie and Janssen. Xu, Ziheng: No conflict of interest Wright, Emily Kate: Speaker Fees, Consultancy and Advisory Boards: AbbVie, Celltrion, Falk, Ferring, Janssen, Pfizer. Research funding/support: AbbVie, Ferring, Janssen. Sparrow, Miles P.: Educational grants or research support – Gilead, Celltrion Speaker’s fees – Janssen, Abbvie, Ferring, Takeda, Pfizer, Celltrion, Eli Lilly, Dr. Falk Pharma Advisory boards or consultancy fees – Janssen, Takeda, Pfizer, Celgene, Abbvie, MSD, Emerge Health, Gilead, BMS, Celltrion, Eli Lilly, Alimentiv O’Donnell, Jonathan: Grants: AVANT Foundation, Medical Insurance Group of Australia (MIGA) Lewindon, Peter: No conflict of interest Subramanian, Kavitha: No conflict of interest Huang Fu, Janny: No conflict of interest Moore, Gregory Thomas: Advisory boards: AbbVie, Celltrion, Eli Lilly, Gilead, J&J, Pfizer, Takeda Speakers fees: AbbVie, Falk, Ferring, J&J, Pfizer, Roche, Sandoz, Takeda Research support: MRFF, NHMRC, CCA, GESA, Gutsy Group, AbbVie, Janssen, Pfizer, Shire, Takeda Subhaharan, Deloshaan: No conflict of interest Mohsen, Waled: No conflict of interest Tan, Zhi: No conflict of interest Thin, Lena: Pfizer- advisory board fees, research grants Takeda- research grant, advisory board fees JNJ- advisory board fees Abbvie- advisory board fees Neuroscientific - advisory committee Celltriom- advisory board fees Ghali, Mark: No conflict of interest Ghaly, Simon: Speaker fees, research grants and travel grants from Dr. Falk pharma, Janssen, Pfizer, AbbVie, Sandoz and Ferring and served on advisory boards for Pfizer and AbbVie. De Cruz, Peter: No conflict of interest Lo, Sheng Wei: No conflict of interest Paramsothy, Sudarshan: SP has served as a consultant for Vedanta Biosciences and has received speaker / advisory board fees from AbbVie, Dr Falk Pharma, Ferring, Janssen and Takeda. Leong, Rupert: advisory board: AbbVie, Aspen, BMS, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, Takeda, Spyre, Roche research grants: Joanna Tiddy USYD, McCusker Charitable Foundation, Celltrion, Shire, Janssen, Takeda, Gastroenterological Society of Australia, NHMRC, Gutsy Group, Pfizer