Macaluso et al., 2023 [18]Endoscopic and clinical responseReal-world observational studyUST4450% achieved a reduction of at least one point in RS72.7% clinical successReduction of at least one point in RSClinical success (absence of clinical failure)17.8 ± 8.4 monthsNo adverse events reportedUST initiated for endoscopically documented POR, with significant rates of endoscopic and clinical successHuinink et al., 2023 [28]Retreatment with anti-TNF therapy for postoperative Crohn’s disease recurrence is valid. Combination therapy is more effective than monotherapy.Retrospective cohort studyAnti-TNF therapy vs. combination therapy364Not specifiedNot specifiedTreatment failure rate (need for reintroduction of corticosteroids, immunosuppressants, or biologicals or need for re-resection)Treatment failure rate at 1 and 2 years, analysis of preoperative anti-TNF failure, combination therapy vs. monotherapy, retreatment with the same or different anti-TNF agent1 and 2 yearsNot specifiedRetreatment with anti-TNF therapy post-ICR is effective, especially with combination therapy. The study highlights the importance of combination therapy to reduce treatment failure ratesBachour et al., 2023 [19]Change in Biologic Class Promotes Endoscopic Remission Following Endoscopic Postoperative Crohn’s Disease RecurrenceRetrospective Cohort StudyNew Biologic Class vs. Therapy Optimization/Continuation81Initiation of a new biologic class was associated with a higher rate of endoscopic improvement60 patients (74.1%) experienced composite recurrence (persistent ePOR or surgical recurrence)Composite endoscopic or surgical recurrenceReduction of modified RSMedian follow-up from ePOR to subsequent endoscopy: 426.5 daysNot specified specifically for each interventionThe study emphasizes the benefit of changing the biologic class after the detection of ePOR despite prophylactic biologic therapyUeda et al., 2023 [29]Endoscopic and clinical responseRetrospective cohort studyBiologic era treatments267Postoperative anastomotic lesions were detected in 61.0% at index ileocolonoscopy and 74.9% at follow-up ileocolonoscopyPatients with intermediate or severe lesions required significantly more interventions (endoscopic dilation or surgery)Frequency and severity of postoperative anastomotic lesionsInterventions required (endoscopic dilation or surgery)~1 year, follow-up duration not specifiedNot reportedFrequent and increasing severity of anastomotic lesions observed, prospective studies needed to evaluate treatment enhancementDe Cruz et al., 2022 [30]Endoscopic and clinical responseRandomized controlled trialThiopurine/ADA vs. Placebo85A combination of ulcer depth and circumference at 6 months was associated with endoscopic recurrence at 18 months38% remission at 12 months for patients who stepped up treatment at 6 months, 39% recurrence at 6 monthsA combination of ulcer depth and circumference at 6 months was associated with endoscopic recurrence at 18 monthsN/A18 monthsN/AThe combination of ulcer depth and circumference at anastomosis at 6 months was predictive of endoscopic recurrence at 18 monthsMarques Cami et al., 2022 [31]Endoscopic and clinical responseCase reportRuxolitinib1More than 50% reduction of ulcerated mucosa in both ileocolonic anastomosis and neoileumClinical remission for six months, no further budesonide cycles neededReduction of ulcerated mucosa, clinical remissionFecal calprotectin levels, blood test normalization6 monthsNo adverse events reportedPatient showed significant clinical and endoscopic improvement related to ruxolitinib treatment, with satisfactory evolution of polycythemia veraMacaluso et al., 2022 [32]Endoscopic and clinical responseCohort studyVDZ58Endoscopic success in 47.6% (reduction of at least one point of RS)Clinical failure in 19.0% at one year, 32.8% at the end of follow-up, 12.1% required new resectionEndoscopic success (reduction of at least one point RS)Clinical failure, need for new resectionMean 24.8 ± 13.1 monthsNot reportedVDZ shows potential effectiveness in treating POR of CDOrlando et al., 2020 [20]Endoscopic and clinical responseRandomized double-blind double-dummy trialAZA vs. High-dose 5-aminosalicylic acid (5-ASA)46AZA: 6 (27.3%) with RS decrease ≥ 2 points, 8 (36.4%) with decrease ≥ 1 point; 5-ASA: 2 (8.3%) with RS decrease ≥ 2 points, 2 (8.3%) with decrease ≥ 1 pointAZA: 3 (13.6%) clinical recurrence; 5-ASA: 5 (20.8%) clinical recurrenceTherapeutic failure (clinical recurrence or drug discontinuation due to adverse events) at 12 months10-year post-trial analysis of clinical and endoscopic outcomes12 monthsAZA: 3 adverse events leading to drug discontinuation (fever, hyperamylasemia, mild pancreatitis)No significant difference in treatment failure between 5-ASA and AZA, AZA has a less favorable safety profile but may be more effective in preventing clinical recurrenceCanete et al., 2020 [21]Endoscopic and clinical responseMulticenter retrospective observational studyIFX vs. ADA179Endoscopic improvement in 61%, endoscopic remission in 42%59% clinical remission in patients with clinical POR at the start of therapyEffectiveness of anti-TNF agents in improving mucosal lesionsEndoscopic improvement, clinical remissionMedian 31 months (IQR 13–54)Not specifiedIFX showed higher rates of endoscopic response and remission compared to ADA; concomitant thiopurine use increased efficacyRiviere et al., 2021 [33]Clinical and surgical recurrenceRetrospective cohort studyImmunosuppressants and biologics365RS ≥ i2 associated with increased risk of clinical and surgical recurrence48% clinical POR, 26% modified surgical POR within a median follow-up of 88 monthsClinical POR rates, surgical POR ratesImpact of endoscopy-guided therapy modificationMedian 88 monthsNot reportedRS ≥ i2 patients more likely to receive new therapy; modest decrease in clinical POR for RS i3 and i4 with immunosuppressants or biologics; no benefit for RS i2Hu et al., 2016 [34]Endoscopic and clinical responseCase reportThalidomide1Mucosal healing achieved at 9 months; RS declined from i2 to i1Clinical remission at 15 monthsMucosal healing (MH) of anastomotic ulcersEndoscopic and clinical improvement15 monthsNo adverse effects reportedThalidomide is effective in inducing mucosal healing in postoperative CD endoscopic recurrenceDe Cruz et al., 2015 [22]Endoscopic and clinical responseRandomized controlled trialThiopurine/ADA vs. Metronidazole alone17460 (49%) in the active care group had endoscopic recurrence at 18 months vs. 35 (67%) in standard care33 (27%) in the active care group had clinical recurrence (CDAI > 200) vs. 21 (40%) in standard careEndoscopic recurrence at 18 monthsClinical recurrence, C-reactive protein levels, need for further surgery18 monthsNo significant differences between active care and standard care groupsEarly colonoscopy and treatment step-up for recurrence is better than conventional drug therapy aloneZabana et al., 2014 [35]Endoscopic and clinical responseCase-control studyThiopurines with mesalamine vs. Thiopurines alone37Endoscopic improvement in 49%, no difference between groups32% clinical recurrence in cases, 11% in controls (p = 0.2)Development of clinical recurrenceChange in RS, mucosal lesionsMedian 59 months (IQR 22–100)No specific adverse effects reported for mesalamineMesalamine addition showed no benefit over thiopurine alone for endoscopic improvement or clinical recurrence ratesReinisch et al., 2013 [36]Clinical recurrenceFollow-up survey of randomized double-blind double-dummy trialAZA vs. Mesalamine46N/A36% clinical recurrence with AZA, 25% with mesalamine within 24 months post-treatmentClinical recurrence within 24 months post-treatmentLong-term prevention of clinical recurrenceApproximately 4 yearsN/ANo significant difference in time to clinical recurrence between AZA and mesalamineYamamoto et al., 2013 [37]Endoscopic and clinical responseProspective cohort studyEnteral nutrition (EN) vs. Control4056% (EN) vs. 82% (control) endoscopic recurrence30% (EN) vs. 60% (control) clinical recurrenceRecurrence requiring biologic therapy or reoperationClinical recurrence rate, reoperation rate5 yearsDiarrhea and abdominal distension in the EN groupEN significantly reduced the incidence of recurrence requiring biologic therapy, though compliance issues notedPapamichael et al., 2012 [3]Endoscopic and clinical responseProspective, single-center, open-label, two-year pilot studyADA2360% (9/15) achieved complete (RS-i0) or near-complete (RS-i1) mucosal healing at 24 months56% (5/9) of patients with clinical relapse at study enrolment achieved and maintained clinical and serological remissionPrevention of early (at 6 months) and late (at 24 months) PO-ER (Group I) and rate of complete mucosal healing (Group II)Endoscopic and clinical improvement (Group II)24 monthsNo serious adverse events reportedADA is effective in preventing and treating PO-ER and PO-CR in high-risk CD patientsSorrentino et al., 2012 [23]Endoscopic and clinical responseProspective open-label multicenter pilot studyIFX vs. Mesalamine24IFX: 54% endoscopic remission, 69% improvement in endoscopic score; Mesalamine: 0% endoscopic remission, no improvement in endoscopic scoreIFX: 0% clinical recurrence; Mesalamine: 18% clinical recurrence at 8 and 9 monthsProportion of patients with endoscopic remission (score < 2) after 54 weeksImprovements in endoscopic scores, clinical recurrence at 54 weeks54 weeksFlu-like symptoms in 3 patients in the IFX group, new positivity for anti-DNA and lupus anticoagulant antibodies in 2 patientsIFX is superior to mesalamine in treating postoperative endoscopic recurrence of CD, though prophylactic use of IFX may be more effectiveReinisch et al., 2010 [24]Clinical and endoscopic recurrenceRandomized double-blind double-dummy multicenter trialAZA vs. Mesalamine7863.3% of AZA patients showed ≥1 point reduction RS vs. 34.4% of mesalamine patients22.0% therapeutic failure in the AZA group vs. 10.8% in the mesalamine group; clinical recurrence: 0% (AZA) vs. 10.8% (mesalamine)Therapeutic failure during 1 year (CDAI ≥ 200 and increase of ≥60 points from baseline or drug discontinuation due to lack of efficacy/adverse reaction)Endoscopic improvement at month 12, CDAI score change, IBDQ score change, CRP level change, mucosal healing12 monthsAdverse drug reactions led to discontinuation in 22.0% of AZA patients (e.g., pancreatitis, leucopenia)AZA showed superior endoscopic improvement but higher adverse event-related discontinuations compared to mesalamineRegueiro et al., 2010 [25]Endoscopic and clinical responseLong-term follow-up of randomized controlled trialIFX vs. Placebo2471% remission in the placebo group switched to INF at 2 years; recurrence in all INF patients who stopped at 1 yearNot specifiedLong-term endoscopic remission and recurrence rates after surgeryEffectiveness of INF beyond the first postoperative year, response to INF after recurrenceUp to 4.5 yearsInfusion reactions leading to switch to (ADA) in some patientsINF maintains remission with ongoing infusions; recurrence if stopped; effective in treating endoscopic recurrence in anti-TNF naive patients post-surgeryYamamoto et al., 2009 [10]Endoscopic and clinical responseProspective pilot studyIFX vs. Mesalamine vs. AZA2675% endoscopic improvement with IFX, 38% with AZA, 0% with mesalamine0% clinical recurrence with IFX, 38% with AZA, 70% with mesalamineClinical recurrence (CDAI > 150) at 6 monthsEndoscopic improvement, changes in mucosal cytokine levels6 monthsNo serious adverse events reportedIFX significantly reduced clinical and endoscopic recurrence and mucosal cytokine levels compared to AZA and mesalamineBiancone et al., 2006 [38]Endoscopic and clinical responsePilot open-label studyLocal injection of IFX8Endoscopic score improved in 3/8 patients, reduced number and extent of lesions in 7/8 patientsNo clinical relapse observed during the follow-up periodFeasibility and safety of local iIFXnfliximab injection for CD recurrenceClinical remission, histologic score, and assessment of local side effectsMedian 20 months (range 14–21 months)No local or systemic side effects reportedIFX injections were feasible and safe, with reduced lesion extent in most patients; further placebo-controlled studies needed to assess efficacyAlves et al., 2004 [39]Clinical recurrenceRetrospective cohort studyImmunosuppressive (IS) drugs (AZA, 6-mercaptopurine, or methotrexate) vs. Control (salicylates or no treatment)26N/AClinical recurrence rate at 3 years: IS group 25%, Control group 60%Clinical recurrence rate at 3 yearsRecurrence rate at follow-up, third intestinal resection rateMean follow-up of 80 ± 46 monthsNo specific IS complications reportedIS drugs lowered clinical recurrence and third resection rates after the second resection for ileocolonic anastomotic recurrence in CD patientsDejaco et al., 2004 [40]Endoscopic and clinical responseOpen-label pilot study(rhG-CSF)5Complete mucosal healing in 2 patients (40%); Partial response in 4 patients (80%)All patients remained in clinical remission for 12 monthsComplete mucosal healing (RSi0)Intestinal permeability, cytokine levels, quality of life (IBDQ)12 monthsTransient headache, mild bone and muscle pain observed in 2 patientsrhG-CSF was well tolerated and demonstrated potential efficacy in treating severe endoscopic POR in CD patientsDe Cruz et al., 2013 [41]Endoscopic and clinical responseMulticenter randomized controlled trialImmediate postoperative ADA vs. Step-up ADA at 6 months6043% endoscopic recurrence with immediate Adalimumab, 59% with step-up Adalimumab32% complete mucosal normality with immediate ADA, 22% with step-up ADAEndoscopic recurrence at 18 monthsSevere disease recurrence rates, mucosal healing18 monthsNot specifically reportedNo significant difference in recurrence; step-up anti-TNF therapy based on endoscopic findings viable for high-risk patientsReinisch et al., 2008 [42]Clinical and endoscopic responseRandomized double-blind double-dummy multicenter trialAZA vs. Mesalamine7846.3% endoscopic improvement with AZA vs. 29.7% with mesalamine (ITT); 63.3% vs. 34.4% (completer analysis)Not specifiedTherapeutic failure (CDAI ≥ 200 or drug discontinuation due to lack of efficacy or intolerable adverse reaction)Endoscopic improvement (≥ 1 point drop in RS)52 weeksNot specifiedNo significant difference in therapeutic failure rates; higher endoscopic improvement with AZA