RESCUE-CD - Real-world effectiveness of risankizumab in moderate-to-severe Crohn's disease: a case series involving the most refractory and challenging patients.

Defining Endpoints and Biomarkers in Inflammatory Bowel Disease: Moving the Needle Through Clinical Trial Design

Omega-3 Fatty Acids for Maintenance of Remission of Crohn's Disease

The Crohn's Disease Activity Index (CDAI) is used to judge efficacy in clinical trials. We explored the effect of CDAI response definitions for induction on study efficiency. We analyzed primary CDAI data from induction studies in patients with mildly to moderately active Crohn's disease, not receiving concomitant aminosalicylates, corticosteroids, or immunomodulator therapy, and without fistulizing or stricturing complications. The 12 definitions of clinical response included: CDAI decrease from baseline by 50, 70, 100, or 150 points; decrease by 25% from baseline and by 70 or 100 points; CDAI <100 or 150 points; CDAI <150 points plus decrease by 70 or 100 points; CDAI <150 points at any time sustained for the duration of the trial; or decrease in the CDAI by 70 points for the last two consecutive visits. Response definitions were ranked according to ability to optimize the effect difference between treatment arms. The effect of time, baseline disease activity (CDAI 200-299 or > or =300 points), and previous surgical resections on response definitions were evaluated and ranked. Multivariate analysis on additional factors of age (<40 or > or =40 yr), gender and duration of disease (<2 or > or =2 yr) were performed to determine predictors of response when applied to these CDAI definitions. Treatment effect differences in placebo-controlled studies were maximized by response definitions that incorporated either a decrease CDAI > or =70 points for the last two consecutive visits or decrease in baseline CDAI > or =100 points, and remained optimal when evaluated for the composite effect of time, baseline activity, and prior resections. A decrease in baseline CDAI > or =100 points had some advantages over a decrease CDAI > or =70 points over two visits in terms of study efficiency, as it produced a lower control response rate and was not influenced by any of the baseline factors. Clinical trial efficiency for induction studies in patients with mildly to moderately active Crohn's disease can be improved by using either a decrease in CDAI by > or =70 points for the last two consecutive visits or a decrease in baseline CDAI by > or =100 points as the primary end point for the trial. These findings are valid for patients with ileocecal Crohn's disease not refractory to aminosalicylates, corticosteroids, immunomodulators, and biologics, and patients who do not have stricturing or penetrating complications. It is unclear if these CDAI response criteria would similarly increase study efficiency in trials that recruited patients with moderately to severely active disease, patients refractory to aminosalicylates, corticosteroids, immunomodulators, and biologics, and patients with stricturing or penetrating complications.

Correlation Between the Crohn's Disease Activity and Harvey–Bradshaw Indices in Assessing Crohn's Disease Severity

Background The efficacy and safety of risankizumab (RZB) and ustekinumab (UST) in patients (pts) with moderate to severe Crohn's disease (CD) refractory to prior anti-tumour necrosis factor (TNF)α therapy were compared in the SEQUENCE head-to-head study. Previously, wk24 CD activity index (CDAI) clinical remission rates (CDAI&amp;lt;150) were reported for 50% of pts (first primary endpoint);1 here, the efficacy of RZB versus (vs) UST for achieving wk24 clinical remission and other symptomatic improvements in the full pt population was assessed. Methods SEQUENCE (NCT04524611) was an open-label, multicenter, randomised, efficacy assessment-blinded study in pts with moderate to severe CD (defined in Figure footnote) refractory to TNFα therapy. Pts in the primary efficacy analysis set were randomised 1:1 to receive RZB (intravenous [IV] 600mg induction at BL, week (wk)4 and wk8, then 360mg subcutaneous [SC] maintenance every 8 wks [Q8w], starting at wk12) or UST (single weight-based IV induction followed by a 90mg Q8w SC maintenance starting at wk8) up to wk48. A mandatory steroid taper began at wk2. Randomisation was stratified by BL steroid use and number of failed anti-TNFs. Prespecified non-ranked endpoints included CDAI clinical response and stool frequency (SF)/abdominal pain score (APS) clinical remission (definitions in Figure footnote). CDAI clinical remission at wk48 was a ranked secondary endpoint. CDAI clinical remission at wks 8 and 24, and changes from BL in avg daily APS, SF, and CDAI, were evaluated post-hoc. Binary endpoints were analysed using non-responder imputation while incorporating multiple imputation to handle missing data due to COVID-19 and/or geopolitical conflict. Continuous endpoints were analysed using a mixed-effect model with repeated measures. All P values are nominal, except for wk48 CDAI clinical remission (ranked secondary endpoint). Results With RZB vs UST, respectively, greater rates of CDAI clinical remission (59.6% [152/255] vs 42.6% [113/265]; P=0.0001), SF/APS clinical remission (55.7% vs 41.1%; P&amp;lt;0.001) and CDAI clinical response (69.8% vs 54.3%; P&amp;lt;0.001) were observed at wk24; similar results were observed at wk48 (Figure). Mean BL APS in the RZB and UST groups was 1.9 (both groups), SF was 5.5 and 5.6, and CDAI was 309.4 and 310.1, respectively. Least square (LS) mean changes from BL in APS, SF, and CDAI were greater with RZB vs UST and observed early as wk8 (APS: -0.9 vs -0.8; SF: -3.0 vs -2.3; P&amp;lt;0.001; CDAI: -136.3 vs -117.1; P&amp;lt;0.05) (Figure). The safety profiles of RZB and UST were consistent with published results.1 Conclusion In this head-to-head study, improvements in symptomatic outcomes in pts with CD were greater with RZB than UST over 48 wks of treatment. 1doi.org/10.1002/ueg2.12474

Thalidomide has been shown to be an effective treatment in Crohn's disease. To assess the efficacy and tolerability of thalidomide in refractory Crohn's disease patients. Twenty-five patients were treated. Retrospective 'estimated' Crohn's Disease Activity Indices were assessed at baseline and at the end of follow-up. Clinical response was defined as symptomatic improvement and a reduction in the 'estimated' Crohn's Disease Activity Index of >100 points, > or =50% reduction in draining fistulas or clinical improvement in perianal ulcers. Clinical remission was defined as symptom resolution and an 'estimated' Crohn's Disease Activity Index <150, complete fistula closure or complete ulcer healing. Six of eight patients treated for luminal disease responded to thalidomide at a median follow-up of 12 months (three clinical responses, three clinical remissions). The median reduction in 'estimated' Crohn's Disease Activity Index was 212 points (P = 0.005). Nine of 11 patients with active fistulizing disease responded to thalidomide (six responses; three remissions). The four patients treated for both luminal and fistulizing disease had fistula response. Three of them had a response in luminal disease activity. One of two patients with ulcerating perianal disease responded. Twelve patients discontinued treatment because of adverse effects (three sedation; two abdominal pain; one leucopoenia; six neuropathy). Thalidomide is an effective short- to medium-term treatment in selected patients with refractory luminal and fistulizing Crohn's disease. Its long-term use is limited by toxicity.

Nutritional and Botanical Approaches for Inflammatory Bowel Disease

Background The efficacy and safety of risankizumab (RZB) as induction and maintenance therapy for patients with moderately to severely active Crohn’s disease (CD) has been documented. Steroid-free clinical remission is an important additional treatment goal in CD. The efficacy of RZB by baseline steroid use during induction and steroid-free outcomes during maintenance was examined. Methods In ADVANCE (NCT03105128) and MOTIVATE (NCT03104413), patients with moderately to severely active CD received intravenous (IV) RZB induction therapy or placebo (PBO) for 12 weeks. Patients with clinical response to RZB were re-randomised in a 52-week maintenance study (FORTIFY; NCT03105102) to subcutaneous (SC) RZB or PBO (ie, withdrawal). Patients receiving steroids (maximum prednisone or equivalent ≤ 20 mg/day; budesonide ≤ 9 mg/day) at baseline of the induction studies maintained stable doses for the 12-week study duration. A mandatory steroid taper per protocol was initiated at the beginning of maintenance for patients receiving steroids during induction. Patients losing clinical response (per investigator assessment) after initiation of taper could have their steroid dose increased up to the induction baseline dose. This analysis included patients who received RZB 600 mg IV in ADVANCE or MOTIVATE and patients who received RZB 360 mg SC in FORTIFY. Endpoints reported included clinical remission (defined by CD Activity Index [CDAI] or stool frequency/abdominal pain score [SF/APS] criteria) at week 12 of induction by baseline steroid use, steroid-free clinical remission (CDAI or SF/APS), steroid-free endoscopic response, and steroid-free endoscopic remission at week 52 of maintenance. Steroid discontinuation rates over 52 weeks of maintenance were also assessed. Results Induction of clinical remission at week 12 with RZB 600 mg IV in ADVANCE or MOTIVATE was independent from baseline steroid use (Figure 1).Clinical remission rates (CDAI or SF/APS) at week 12 were similar for patients using steroids vs those who were not (33.8%–42.0% vs 34.9%–46.6%; Figure 1). Steroid use decreased over time in FORTIFY, with a greater proportion of patients receiving RZB 360 mg SC discontinuing steroids at week 52 vs withdrawal (PBO SC; Figure 2A). Rates of steroid-free clinical remission (P ≤ .012), steroid-free endoscopic response (P &amp;lt; .001), and steroid-free endoscopic remission (P &amp;lt; .001) were significantly higher with RZB 360 mg SC vs withdrawal (PBO SC) at week 52 of maintenance (Figure 2B–2C). Conclusion Efficacy of RZB induction therapy was independent of baseline steroid use. RZB maintenance promotes high rates of steroid-free clinical and endoscopic outcomes, demonstrating a benefit of RZB treatment in CD.

Background The ongoing FORTIFY maintenance open-label extension (OLE) substudy evaluates the long-term efficacy and safety of risankizumab (RZB), a p19 interleukin-23 inhibitor, for treatment of moderate to severe Crohn’s disease (CD). Here, we report 2-year results of FORTIFY OLE. Methods The FORTIFY (NCT03105102) OLE enrolled patients (pts) who completed 52-wks maintenance dosing in the FORTIFY substudies or RZB phase 2 OLE.1,2 All pts received 180 mg subcutaneous (SC) RZB every 8 wks (Q8w), starting at wk56, except for pts who had prior rescue therapy (single 1200mg intravenous [IV] RZB dose then 360mg SC Q8w) who continued 360mg SC Q8w in the OLE. Pts with inadequate response (increased symptoms plus objective marker of inflammation) during the OLE could receive rescue therapy as described above. Pooled data from both treatment groups (RZB 180 mg &amp; 360 mg SC) were assessed. Clinical outcomes were evaluated every 24 wks (endpoint definitions in Figure footnote). Endoscopy was performed every 96 wks. Results are reported as observed. Efficacy data for pts receiving rescue therapy in the OLE were included up to rescue initiation. Safety was assessed through the cutoff date of 05MAR2023. As this trial is ongoing, most patients have not reached the wk152 study visit. Any treatment-emergent adverse events (TEAEs) reported on or after the first dose in the OLE were analysed. Results As of the cutoff date, 1147 pts entered the OLE, of which 203 (17.6%) pts received rescue therapy during the OLE. Clinical response and remission rates were generally maintained with RZB from wks 56 to 152 (CD activity index [CDAI] clinical response, 85.8% to 86.5%, respectively; enhanced clinical response, 88.6% to 89.2%; CDAI clinical remission, 68.5% to 77.6%; stool frequency/abdominal pain score clinical remission, 64.4% to 71.0%) (Figure). At wks 56 and 152, respectively, rates of endoscopic response were 53.4% and 74.2%, endoscopic remission were 37.5%, and 58.9%, and ulcer-free endoscopy were 31.0% and 50.0%. There were no new trends for exposure-adjusted rates of TEAEs, and rates of adjudicated major cardiovascular adverse events, malignancies, serious infections and hepatic events remained stable with no new safety risks identified. There were no events of active tuberculosis, serious hypersensitivity, or adjudicated anaphylactic reaction. Three deaths occurred during the OLE (see Table footnote), all assessed by investigators as unrelated to study drug. Conclusion Pts receiving long-term RZB maintenance therapy in FORTIFY demonstrated sustained clinical and endoscopic efficacy with at least 3 years of treatment. The safety profile is consistent and supports long-term RZB treatment. 1doi: 10.1093/ecco-jcc/jjab093 2doi: 10.1016/S0140-6736(22)00466-4.

Intolerance to azathioprine is a rare but important problem in treating chronically active Crohn's disease. We performed this study to evaluate mycophenolate mofetil as an alternative immunosuppressive therapy for patients with Crohn's disease who did not tolerate azathioprine. Four patients with highly active perianal Crohn's disease and two patients with chronically active, steroid-dependent Crohn's disease were included. All patients consumed 2 g/day of mycophenolate mofetil for a median of 8 months (range, 6-12 months). Disease activity was measured by the Perianal Crohn's Disease Activity Index in patients with perianal disease and by the Crohn's Disease Activity Index in patients with chronically active Crohn's disease. Azathioprine-induced side effects disappeared after the drug was discontinued. All patients improved during treatment with mycophenolate mofetil, as shown by a remarkable reduction in the respective clinical scores. Five patients showed no side effects during treatment with mycophenolate mofetil. After 4 months' treatment one patient developed diarrhea that was probably not due to mycophenolate mofetil. Mycophenolate mofetil could be an alternative therapy to azathioprine in patients with Crohn's disease.

In assessing Crohn's disease (CD) activity, C-reactive protein (CRP) is an important indicator of inflammation; however, it is not necessarily associated with the Crohn's Disease Activity Index (CDAI), particularly in patients with low CRP. Recently, platelet activation factors have been recognized due to their importance in the inflammatory response. In this study, we examined associations between the CDAI and platelet factor 4 (PF-4), β-thromboglobulin (β-TG), and other coagulation and fibrinolysis factors. We aimed to find a new marker for evaluating disease activity in patients with CD and low CRP. Nine markers, including CRP, platelet count, white blood cell count, fibrin and fibrinogen degradation product, fibrinogen, thrombin-antithrombin complex, prothrombin fragments 1 + 2, PF-4, and β-TG were evaluated in 47 patients with CD and low CRP (<1.0 mg/dl). Patients were assigned to high or low disease activity groups, CDAI-H (CDAI ≥ 150) and CDAI-L (CDAI < 150), respectively. CDAI-H exhibited significantly higher PF-4 and β-TG levels than CDAI-L (P < 0.01). Other markers were not significantly different between groups. CDAI was positively correlated with the levels of PF-4 and β-TG (P = 0.0033 and 0.0024; r = 0.4202 and 0.4321, respectively). Receiver operating characteristic curve analyses of PF-4 and β-TG showed high sensitivity (61.9 and 81%, respectively) and specificity (84.7 and 69.2%, respectively) for diagnosing active CD. Among eight potential markers, PF-4 and β-TG were the most highly correlated with CDAI in patients with CD and low CRP. PF-4 and β-TG levels showed promise as new markers for assessing CD in patients with low CRP.

Background Part 2 of the ongoing SEQUENCE study examines the long-term efficacy and safety of risankizumab (RZB), an interleukin-23 p19 inhibitor, in patients (pts) with moderate-to-severe Crohn’s disease (CD). Here, we report the 3-year (yr) results from the SEQUENCE study (2-yr results from Part 2). Methods In Part 2 of SEQUENCE (NCT04524611), pts randomised to RZB who completed the Part 1 week (wk) 48 visit continued on open-label 360mg subcutaneous (SC) RZB every 8 wks (Q8w).1 Clinical remission (per CD activity index [CDAI] and per stool frequency [SF]/abdominal pain score [APS]), steroid-free clinical remission, endoscopic response, endoscopic remission, steroid-free endoscopic remission, deep remission, mucosal healing, Inflammatory Bowel Disease Questionnaire (IBDQ) remission, and normalisation of high-sensitivity C-reactive protein (hs-CRP) and faecal calprotectin (FCP) levels were assessed through wk 148 (endpoints defined in Figure footnote). Inadequate responders could receive ≤2 rescue treatments (600 mg RZB intravenous dose followed by 360 mg SC Q8W), ≥16 weeks apart.1 All intent-to-treat (ITT) pts were assessed as observed (AO) and using modified nonresponder imputation (mNRI; multiple imputation for missed assessments, including RZB discontinuation for reasons other than “lack of efficacy/adverse event limited only to CD”). Data before receiving rescue treatment are presented (see Figure footnote). Treatment emergent adverse events (TEAEs) reported on or after the first RZB dose in Part 2 were analysed (cutoff date: 02JUL2025). Results In total, 224 ITT pts entered Part 2. Compared to wk 52, data AO showed similar or higher rates of clinical remission at wk 148 (CDAI: 76.4% vs 86.3%; SF/APS: 72.1% vs 75.9%), steroid-free clinical remission (CDAI: 75.9% vs 83.5%; SF/APS: 72.1% vs 73.0%), IBDQ remission (62.1% vs 69.0%), endoscopic response (55.8% vs 65.1%), endoscopic remission (39.2% vs 48.8%), steroid-free endoscopic remission (38.7% vs 48.3%), mucosal healing (37.3% vs 43.6%), and deep remission (31.5% vs 36.8%) (Figure). Also, compared to wk 52, a greater proportion of pts with elevated biomarker levels at baseline had normalised levels at wk 148 (hs-CRP: 53.1% vs 69.4%; FCP: 56.9% vs 66.3%). Lower efficacy rates were observed per mNRI but also showed sustained efficacy through wk 148. The profiles of TEAEs and TEAEs of special interest were consistent with the known safety profile of RZB (Table).2,3 No deaths occurred during Part 2. Conclusion Three yrs of continuous RZB therapy in SEQUENCE resulted in durable long-term clinical, endoscopic, and quality of life benefits. The safety profile is consistent with the known safety profile of RZB and supports long-term RZB treatment.

Background Crohn's disease (CD) is a chronic, remitting disease with sometimes inadequate response to the treatment and these factors may impact the quality of life of patients. Our study aims to evaluate the impact of fistulizing disease, different treatment options and disease activity on the quality of life of in CD. Methods Patients who applied to the inflammatory bowel disease outpatient clinic between August 2021 and September 2023 were invited to the study respectively. Patients who agreed to participate were included in the study. The quality of life of the patients was assessed with the Inflammatory Bowel Disease Questionnaire (IBDQ), and disease activity was assessed with the Crohn's Disease Activity Index (CDAI). In addition, the Perianal Disease Activity Index (PDAI) was used in those with perianal disease. The quality of life scores of the patients were compared in terms of clinical and demographic parameters. Results A total of 209 patients enrolled in our study; 103 (49.3%) were non-fistulizing and 106 (50.7%) were fistulizing. 78 of the fistulizing patients had perianal fistula. A moderately strong and statistically significant negative correlation was found between CDAI and total IBDQ (r=-.538, p&amp;lt;0.001). A statistically significant negative correlation was found between PDAI and total IBDQ (r=-.372, p=0.001). Although the mean total IBDQ value of nonfistulizing patients (148.97 ±36.41) was higher than fistulizing patients (144.61±37.46), fistulizing status did not significantly affect the total IBDQ score (p=0.395). Being a woman significantly affects all sub-scores of IBDQ score and total IBDQ score. Although the mean total IBDQ score of patients under biological treatment was higher than who were not using them; the difference was not significant (p=0.771). In addition, the quality of life score was significantly lower in those with a diagnosis of spondyloarthropathy (p=0.012). Conclusion In the current literature, the presence of perianal fistula has been shown to have a negative effect on quality of life in several studies (1,2,3). Our study revealed a negative relationship between PDAI and CDAI values and total IBDQ score. In addition, our study showed that gender had a significant effect on total IBDQ, while fistulizing condition, use of biological agents, and surgical history did not affect the total IBDQ score. It is possible that this partial difference with the current literature is due to the difference of quality of life assesments. References 1-Spinelli A, Yanai H, Girardi P, Milicevic S, Carvello M, Maroli A, Avedano L. The Impact of Crohn's Perianal Fistula on Quality of Life: Results of an International Patient Survey. Crohns Colitis 360. 2023 Jul 25;5(3):otad036. doi: 10.1093/crocol/otad036. PMID: 37529012; PMCID: PMC10390083. 2-Kato M, Yoneyama-Hirozane M, Iwasaki K, Matsubayashi M, Igarashi A. Health-related quality of life in health states corresponding to different stages of perianal fistula associated with Crohn's disease: a quantitative evaluation of patients and non-patients in Japan. J Mark Access Health Policy. 2023 Jan 15;11(1):2166374. doi: 10.1080/20016689.2023.2166374. PMID: 36684854; PMCID: PMC9848226. 3-Karki C, Athavale A, Abilash V, Hantsbarger G, Geransar P, Lee K, Milicevic S, Perovic M, Raven L, Sajak-Szczerba M, Silber A, Yoon A, Tozer P. Multi-national observational study to assess quality of life and treatment preferences in patients with Crohn's perianal fistulas. World J Gastrointest Surg. 2023 Nov 27;15(11):2537-2552. doi: 10.4240/wjgs.v15.i11.2537. PMID: 38111766; PMCID: PMC10725550.

Crohn's disease is a transmural, relapsing inflammatory condition afflicting the digestive tract. Opioid signalling, long known to affect secretion and motility in the gut, has been implicated in the inflammatory cascade of Crohn's disease. Low dose naltrexone, an opioid antagonist, has garnered interest as a potential therapy.The primary objective was to evaluate the efficacy and safety of low dose naltrexone for induction of remission in Crohn's disease.A systematic search of MEDLINE, Embase, PubMed, CENTRAL, and the Cochrane IBD Group Specialized Register was performed from inception to 15 January 2018 to identify relevant studies. Abstracts from major gastroenterology conferences including Digestive Disease Week and United European Gastroenterology Week and reference lists from retrieved articles were also screened.Randomized controlled trials of low dose naltrexone (LDN) for treatment of active Crohn's disease were included.Data were analyzed on an intention-to-treat basis using Review Manager (RevMan 5.3.5). The primary outcome was induction of clinical remission defined by a Crohn's disease activity index (CDAI) of < 150 or a pediatric Crohn's disease activity index (PCDAI) of < 10. Secondary outcomes included clinical response (70- or 100-point decrease in CDAI from baseline), endoscopic remission or response, quality of life, and adverse events as defined by the included studies. Risk ratios (RR) and 95% confidence intervals (CI) were calculated for dichotomous outcomes. The methodological quality of included studies was evaluated using the Cochrane risk of bias tool. The overall quality of the evidence supporting the primary outcome and selected secondary outcomes was assessed using the GRADE criteria.Two studies were identified (46 participants). One study assessed the efficacy and safety of 12 weeks of LDN (4.5 mg/day) treatment compared to placebo in adult patients (N = 34). The other study assessed eight weeks of LDN (0.1 mg/kg, maximum 4.5 mg/day) treatment compared to placebo in pediatric patients (N = 12). The primary purpose of the pediatric study was to assess safety and tolerability. Both studies were rated as having a low risk of bias. The study in adult patients reported that 30% (5/18) of LDN treated patients achieved clinical remission at 12 weeks compared to 18% (3/16) of placebo patients, a difference that was not statistically significant (RR 1.48, 95% CI 0.42 to 5.24). The study in children reported that 25% of LDN treated patients achieved clinical remission (PCDAI < 10) compared to none of the patients in the placebo group, although it was unclear if this result was for the randomized placebo-controlled trial or for the open label extension study. In the adult study 70-point clinical response rates were significantly higher in those treated with LDN than placebo. Eighty-three per cent (15/18) of LDN patients had a 70-point clinical response at week 12 compared to 38% (6/16) of placebo patients (RR 2.22, 95% CI 1.14 to 4.32). The effect of LDN on the proportion of adult patients who achieved a 100-point clinical response was uncertain. Sixty-one per cent (11/18) of LDN patients achieved a 100-point clinical response compared to 31% (5/16) of placebo patients (RR 1.96, 95% CI 0.87 to 4.42). The proportion of patients who achieved endoscopic response (CDEIS decline > 5 from baseline) was significantly higher in the LDN group compared to placebo. Seventy-two per cent (13/18) of LDN patients achieved an endoscopic response compared to 25% (4/16) of placebo patients (RR 2.89; 95% CI 1.18 to 7.08). However, there was no statistically significant difference in the proportion of patients who achieved endoscopic remission. Endoscopic remission (CDEIS < 3) was achieved in 22% (4/18) of the LDN group compared to 0% (0/16) of the placebo group (RR 8.05; 95% CI 0.47 to 138.87). Pooled data from both studies show no statistically significant differences in withdrawals due to adverse events or specific adverse events including sleep disturbance, unusual dreams, headache, decreased appetite, nausea and fatigue. No serious adverse events were reported in either study. GRADE analyses rated the overall quality of the evidence for the primary and secondary outcomes (i.e. clinical remission, clinical response, endoscopic response, and adverse events) as low due to serious imprecision (sparse data).Currently, there is insufficient evidence to allow any firm conclusions regarding the efficacy and safety of LDN used to treat patients with active Crohn's disease. Data from one small study suggests that LDN may provide a benefit in terms of clinical and endoscopic response in adult patients with active Crohn's disease. Data from two small studies suggest that LDN does not increase the rate of specific adverse events relative to placebo. However, these results need to be interpreted with caution as they are based on very small numbers of patients and the overall quality of the evidence was rated as low due to serious imprecision. Further randomized controlled trials are required to assess the efficacy and safety of LDN therapy in active Crohn's disease in both adults and children.

Thrombocytosis and iron deficiency anemia are frequent complications of inflammatory bowel disease (IBD). The aim of this study was to investigate the correlation between iron deficiency anemia and thrombocytosis in IBD patients. A total of 198 consecutive IBD patients and 102 healthy controls participated in the study. The parameters investigated were: platelets (PLT), mean platelet volume, platelet distribution width, plateletcrit, hematocrit (HCT) levels, hemoglobulin (Hb) levels, mean corpuscular volume (MCV), red cell distribution width (RDW), ferritin levels, soluble transferrin receptor (sTfR) levels, the sTfR-F index (sTfR-F=sTfR/log10 ferritin), and vitamin B12 and folate levels. Thrombocytosis was defined as an absolute number of PLT greater than 400k/μl. Disease activity indices (Crohn's Disease Activity Index for Crohn's disease and Simple Clinical Colitis Activity Index for ulcerative colitis) as well as C-reactive protein (CRP) were also correlated with the study parameters. The IBD patients demonstrated decreased HCT levels, Hb levels, MCV, mean platelet volume, and ferritin levels and an increased absolute PLT count, RDW, platelet distribution width, plateletcrit, sTfR and sTfR-F index (P<0.0001) compared with healthy controls. Twenty-seven patients exhibited thrombocytosis (13.6%). The median value for PLT (interquartile range) was 289 (228-355)k/μl, for Hb levels was 13.4 (12.0-14.7) g/dl, for ferritin levels was 36.6 (19.7-80.7) ng/ml, and for sTfR-F was 0.82 (0.61-1.37) mg/l. The PLT in IBD patients correlated with HCT levels, Hb levels, MCV, RDW, Fe levels, ferritin levels, sTfR, sTfR-F, CRP levels, Simple Clinical Colitis Activity Index, and Crohn's Disease Activity Index (Spearman's ρ correlation). In the multivariate analysis, only Hb levels, RDW, CRP levels, ferritin levels, and sTfR-F remained significant (P<0.05). None of the aforementioned was observed in the control group. The absolute PLT count seems to correlate with iron deficiency anemia parameters and disease activity in IBD patients. Controlling the inflammation and managing iron deficiency could lead to reversal of thrombocytosis in IBD patients.