Recent insights into the molecular pathogenesis of Crohn’s disease: a review of emerging therapeutic targets

References

• Centers for Disease Control and PreventionCDC—Epidemiology of the IBD – Inflammatory Bowel Disease2015Atlanta, GACenters for Disease Control and Prevention Available from: http://www.cdc.gov/ibd/ibd-epidemiology.htmAccessed April 15, 2015
   Google Scholar
• MagroFLangnerCDriessenAEuropean consensus on the histopathology of inflammatory bowel diseaseJ Crohns Colitis201371082785123870728
   PubMed Web of Science ®Google Scholar
• CoulombeFBehrMACrohn’s disease as an immune deficiency?Lancet374969276977019733770
   PubMed Web of Science ®Google Scholar
• AntoniLNudingSWehkampJStangeEFIntestinal barrier in inflammatory bowel diseaseWorld J Gastroenterol20142051165117924574793
   PubMed Web of Science ®Google Scholar
• MergaYCampbellBJRhodesJMMucosal barrier, bacteria and inflammatory bowel disease: possibilities for therapyDig Dis201432447548324969297
   PubMed Web of Science ®Google Scholar
• FavaFDaneseSCrohn’s disease: bacterial clearance in Crohn’s disease pathogenesisNat Rev Gastroenterol Hepatol20107312612820203678
   PubMed Web of Science ®Google Scholar
• MantzarisGJWhen can we cure Crohn’s?Best Pract Res Clin Gastroenterol28351952924913390
   PubMed Web of Science ®Google Scholar
• BaumgartDCSandbornWJCrohn’s diseaseLancet201238098531590160522914295
   PubMed Web of Science ®Google Scholar
• Ben-HorinSChowersYReview article: loss of response to anti-TNF treatments in Crohn’s diseaseAlimen Pharmacol Ther2015339987995
   Web of Science ®Google Scholar
• DingTDeightonCComplications of anti-TNF therapiesFut Rheumatol200726587597
   Google Scholar
• Van LimbergenJWilsonDCSatsangiJThe genetics of Crohn’s diseaseAnnu Rev Genomics Hum Genet2009108911619453248
   PubMed Web of Science ®Google Scholar
• LiuJZAndersonCAGenetic studies of Crohn’s disease: past, present and futureBest Pract Res Clin Gastroenterol201428337338624913378
   PubMed Web of Science ®Google Scholar
• StroberWAsanoNFussIKitaniAWatanabeTCellular and molecular mechanisms underlying NOD2 risk-associated polymorphisms in Crohn’s diseaseImmunol Rev2014260124926024942694
   PubMed Web of Science ®Google Scholar
• AdlerJRangwallaSCDwamenaBAHigginsPDThe prognostic power of the NOD2 genotype for complicated Crohn’s disease: a meta-analysisAm J Gastroenterol2011106469971221343918
   PubMed Web of Science ®Google Scholar
• LeeKMLeeJMCrohn’s disease in Korea: past, present, and futureKorean J Intern Med201429555857025228829
   PubMed Web of Science ®Google Scholar
• LeeJCParkesMGenome-wide association studies and Crohn’s diseaseBriefFunct Genomics20111027176
   Web of Science ®Google Scholar
• FritzTNiederreiterLAdolphTBlumbergRSKaserACrohn’s disease: NOD2, autophagy and ER stress convergeGut201160111580158821252204
   PubMed Web of Science ®Google Scholar
• BaiJLiYShaoTIntegrating analysis reveals microRNA-mediated pathway crosstalk among Crohn’s disease, ulcerative colitis and colorectal cancerMol BioSyst20141092317232824949825
   PubMedGoogle Scholar
• ArchaniotiPGazouliMTheodoropoulosGVaiopoulouANikiteasNMicro-RNAs as regulators and possible diagnostic bio-markers in inflammatory bowel diseaseJ Crohns Colitis20115652052422115369
   PubMed Web of Science ®Google Scholar
• ChapmanCGPekowJThe emerging role of miRNAs in inflammatory bowel disease: a reviewTherap Adv Gastroenterol201581422
   PubMed Web of Science ®Google Scholar
• SankeyEADhillonAPAnthonyAEarly mucosal changes in Crohn’s diseaseGut19933433753818472987
   PubMed Web of Science ®Google Scholar
• TeshimaCWDielemanLAMeddingsJBAbnormal intestinal permeability in Crohn’s disease pathogenesisAnn N Y Acad Sci2012125815916522731729
   PubMed Web of Science ®Google Scholar
• ScribanoMLPranteraCUse of antibiotics in the treatment of Crohn’s diseaseWorld J Gastroenterol201319564865323429474
   PubMed Web of Science ®Google Scholar
• Bosca-WattsMMToscaJAntonRMoraMMinguezMMoraFPathogenesis of Crohn’s disease: bug or no bugWorld J Gastrointest Pathophysiol20156111225685606
   PubMedGoogle Scholar
• JusteCKreilDPBeauvalletCBacterial protein signals are associated with Crohn’s diseaseGut201463101566157724436141
   PubMed Web of Science ®Google Scholar
• Barnich NicolasD-MAAdherent-invasive Escherichia coli and Crohns diseaseCurr Opin Gastroenterol2007231162017133079
   PubMed Web of Science ®Google Scholar
• NguyenHTDalmassoGSeiboldFMüllerSDarfeuille-MichaudA436e Crohn’s disease-associated adherent-invasive Escherichia coli suppress autophagy response to replicate intracellularly by regulating host microRNA expressionGastroenterology20131445S82
   Web of Science ®Google Scholar
• Hermon-TaylorJMycobacterium avium subspecies paratuberculosis, Crohn’s disease and the Doomsday scenarioGut Pathog2009111519602288
   PubMed Web of Science ®Google Scholar
• ParrishNMRadcliffRPBreyBJAbsence of Mycobacterium avium subsp. paratuberculosis in Crohn’s patientsInflamm Bowel Dis200815455856519058231
   PubMed Web of Science ®Google Scholar
• BachHWhat role does Mycobacterium avium subsp paratuberculosis play in Crohn’s disease?Curr Infect Dis Rep201517246325754452
   PubMed Web of Science ®Google Scholar
• StewartLCDayASPearsonJSLC11A1 polymorphisms in inflammatory bowel disease and Mycobacterium avium subspecies paratuberculosis statusWorld J Gastroenterol201016455727573121128323
   PubMed Web of Science ®Google Scholar
• PapamichaelKKonstantopoulosPMantzarisGJHelicobacter pylori infection and inflammatory bowel disease: is there a link?World J Gastroenterol201420216374638524914359
   PubMed Web of Science ®Google Scholar
• XiangZChenYPYeYFHelicobacter pylori and Crohn’s disease: a retrospective single-center study from ChinaWorld J Gastroenterol201319284576458123901235
   PubMed Web of Science ®Google Scholar
• NavaneethanUVenkateshPGShenBClostridium difficile infection and inflammatory bowel disease: understanding the evolving relationshipWorld J Gastroenterol201016394892490420954275
   PubMed Web of Science ®Google Scholar
• JessTSimonsenJNielsenNMEnteric Salmonella or Campylobacter infections and the risk of inflammatory bowel diseaseGut201160331832421193449
   PubMed Web of Science ®Google Scholar
• SartorRBMechanisms of disease: pathogenesis of Crohn’s disease and ulcerative colitisNat Clin Pract Gastroenterol Hepatol20063739040716819502
   PubMedGoogle Scholar
• ElliottDEUrbanJJrArgoCKWeinstockJVDoes the failure to acquire helminthic parasites predispose to Crohn’s disease?FASEB J200014121848185510973934
   PubMed Web of Science ®Google Scholar
• SlatteryEMitchellPMulcahyHECigarette smoking in Crohns disease: can we do more?J Crohns Colitis20115550550521939931
   PubMed Web of Science ®Google Scholar
• GrahamCUnderstanding smoking and nicotine effects on the gastrointestinal tractGastrointest Nurs201311144
   Google Scholar
• Pfeffer-GikTLevineADietary clues to the pathogenesis of Crohn’s diseaseDig Dis201432438939424969285
   PubMed Web of Science ®Google Scholar
• SchulmanJShaoulRP435 Maintenance of remission with partial enteral nutrition therapy in pediatric Crohn’s disease: a retrospective studyJ Crohns Colitis20159Suppl 1S298
   Google Scholar
• CaprilliRLapaquettePDarfeuille-MichaudAEating the enemy in Crohn’s disease: an old theory revisitedJ Crohns Colitis20104437738321122532
   PubMed Web of Science ®Google Scholar
• KawaguchiTMoriMSaitoKFood antigen-induced immune responses in Crohn’s disease patients and experimental colitis miceJ Gastroenterol201450439440525099432
   PubMed Web of Science ®Google Scholar
• FergusonLRPotential value of nutrigenomics in Crohn’s diseaseNat Rev Gastroenterol Hepatol20129526027022410431
   PubMed Web of Science ®Google Scholar
• ScottKPGratzSWSheridanPOFlintHJDuncanSHThe influence of diet on the gut microbiotaPharm Res20136915260
   Web of Science ®Google Scholar
• WaltersSSQuirosARolstonMGrishinaILiJAnalysis of gut microbiome and diet modification in patients with Crohn’s diseaseSOJ Microbiol Infect Dis201423113
   PubMedGoogle Scholar
• ClinicalTrials.govDietary therapy and gut microbiome in Crohn’s disease and ulcerative colitis Available from: https://clinicaltrials.gov/ct2/show/NCT02412553. NLM identifier: NCT02412553Accessed May 1, 2015
   Google Scholar
• WallaceKLZhengLBKanazawaYShihDQImmunopathology of inflammatory bowel diseaseWorld J Gastroenterol201420162124415853
   PubMed Web of Science ®Google Scholar
• MonteleoneGKumberovaACroftNMMcKenzieCSteerHWMacDonaldTTBlocking Smad7 restores TGF-β1 signaling in chronic inflammatory bowel diseaseJ Clin Invest1082001601609
   Google Scholar
• TokuhiraNKitagishiYSuzukiMPI3K/AKT/PTEN pathway as a target for Crohn’s disease therapy (Review)Int J Mol Med2014351101625352295
   PubMed Web of Science ®Google Scholar
• GeremiaAArancibiaCGwelaAChapmanRWTravisSPLPowrieFOP001. Innate lymphoid cells accumulate in IBDJ Crohns Colitis20148Suppl 1S1
   Web of Science ®Google Scholar
• De CruzPKammMAPrideauxLAllenPBMooreGMucosal healing in Crohn’s disease: a systematic reviewInflamm Bowel Dis201219242944422539420
   PubMed Web of Science ®Google Scholar
• BryantRVWinerSTravisSPRiddellRHSystematic review: histological remission in inflammatory bowel disease. Is ‘complete’ remission the new treatment paradigm? an IOIBD initiativeJ Crohns Colitis20148121582159725267173
   PubMed Web of Science ®Google Scholar
• KawalecPMikrutAWisniewskaNPilcATumor necrosis factor-alpha antibodies (infliximab, adalimumab and certolizumab) in Crohn’s disease: systematic review and meta-analysisArch Med Sci20139576577924273556
   PubMed Web of Science ®Google Scholar
• AliTKaithaSMahmoodSFtesiAStoneJBronzeMSClinical use of anti-TNF therapy and increased risk of infectionsDrug Healthc Patient Saf20135799923569399
   PubMedGoogle Scholar
• PranteraCLochsHGrimaldiMDaneseSScribanoMLGionchettiPRifaximin-extended intestinal release induces remission in patients with moderately active Crohn’s diseaseGastroenterology20111423473481.e422155172
   PubMed Web of Science ®Google Scholar
• SSI Efficacy Crohn’s Disease Remission Compassionate Use ResultsVancouverQu Biologics Inc2015 Available from: http://www.qucrohnstrial.com/ssi-intro/qbeco-ssi-efficacy-and-safety/Accessed February 10, 2015
   Google Scholar
• ClinicalTrials.govEfficacy and safety of anti-MAP therapy in adult Crohn’s disease Available from: https://clinicaltrials.gov/ct2/show/NCT01951326. NLM identifier: NCT01951326Accessed April 15, 2015
   Google Scholar
• RedHill Biopharma LtdRedHill Biopharma Provides Update on Progress With RHB-104 Ongoing Phase III Program for Crohn’s Disease Following FDA MeetingTel AvivRedHill Biopharma Ltd2015 Available from: http://globenewswire.com/news-release/2015/01/29/701089/10117655/en/RedHill-Biopharma-Provides-Update-on-Progress-With-RHB-104-Ongoing-Phase-III-Program-for-Crohn-s-Disease-Following-FDA-Meeting.htmlAccessed January 29, 2015
   Google Scholar
• OrelRKamhi TropTIntestinal microbiota, probiotics and prebiotics in inflammatory bowel diseaseWorld J Gastroenterol20142033115051152425206258
   PubMed Web of Science ®Google Scholar
• GhouriYARichardsDMRahimiEFKrillJTJelinekKADuPontAWSystematic review of randomized controlled trials of probiotics, prebiotics, and synbiotics in inflammatory bowel diseaseClin Exp Gastroenterol2014747348725525379
   PubMedGoogle Scholar
• SarutaMPapadakisKALymphocyte homing antagonists in the treatment of inflammatory bowel diseasesGastroenterol Clin North Am201443358160125110260
   PubMed Web of Science ®Google Scholar
• YuYSchurpfTSpringerTAHow natalizumab binds and antagonizes alpha4 integrinsJ Biol Chem201328845323143232524047894
   PubMed Web of Science ®Google Scholar
• JuilleratPWasanSKFowlerSAEfficacy and safety of natalizumab in Crohn’s disease patients treated at 6 Boston academic hospitalsInflamm Bowel Dis201319112457246323962896
   PubMed Web of Science ®Google Scholar
• HanauerSBFeaganBGMacintoshDGTu1138 Efficacy of Vedolizumab in Crohn’s disease by prior treatment failure in Gemini II, a randomized, placebo-controlled, double-blind, multicenter studyGastroenterology1445S772
   Google Scholar
• MosliMHFeaganBGVedolizumab for Crohn’s diseaseExpert Opin Biol Ther201313345546323394379
   PubMed Web of Science ®Google Scholar
• RaineTVedolizumab for inflammatory bowel disease: changing the game, or more of the same?United European Gastroenterol J201425333344
   PubMed Web of Science ®Google Scholar
• SandsBFeaganBRutgeertsPVedolizumab induction therapy for patients with Crohn’s disease and prior anti-TNF antagonist failure: a randomized, placebo-controlled, double-blind, multicenter trial: P-26Inflamm Bowel Dis201218S24S25
   Web of Science ®Google Scholar
• PooleRMVedolizumab: first global approvalDrugs201474111293130324985716
   PubMed Web of Science ®Google Scholar
• WangMCZhangLYHanWPRISMA – efficacy and safety of vedolizumab for inflammatory bowel diseases: a systematic review and meta-analysis of randomized controlled trialsMedicine (Baltimore)20149328e32625526490
   PubMed Web of Science ®Google Scholar
• PanWJHsuHReesWAPharmacology of AMG 181, a human anti-α(4)β(7) antibody that specifically alters trafficking of gut-homing T cellsBr J Pharmacol20131691516823425116
   PubMed Web of Science ®Google Scholar
• AmiotAPeyrin-BirouletLCurrent, new and future biological agents on the horizon for the treatment of inflammatory bowel diseasesTherap Adv Gastroenterol2015826682
   PubMed Web of Science ®Google Scholar
• OP022Anti-MAdCAM-1 Antibody (PF-00547659) for active refractory Crohn’s disease: results of the OPERA studyJ Crohn’s Colitis20159Suppl 1S14
   Google Scholar
• AllezMPetrykaRSkolnickBEWisniewska-JarosinskaMAMo1213 efficacy and safety of NNC0142-0002, a novel human monoclonal antibody targeting NKG2D: a randomized, double-blind, single-dose phase 2 trial in patients with Crohn’s diseaseGastroenterology1465S587
   Web of Science ®Google Scholar
• D’HaensGRSartorRBSilverbergMSPeterssonJRutgeertsPFuture directions in inflammatory bowel disease managementJ Crohns Colitis20148872673424742736
   PubMed Web of Science ®Google Scholar
• YacyshynBCheyWYWedelMKYuRZPaulDChuangEA randomized, double-masked, placebo-controlled study of alicaforsen, an antisense inhibitor of intercellular adhesion molecule 1, for the treatment of subjects with active Crohn’s diseaseClin Gastroenterol Hepatol20075221522017296530
   PubMed Web of Science ®Google Scholar
• ArseneauKOCominelliFVercirnon for the treatment of Crohn’s diseaseExpert Opin Investig Drugs2013227907913
   PubMed Web of Science ®Google Scholar
• ChemoCentryx, IncChemoCentryx releases Phase III SHIELD 4 clinical results in patients with Crohn’s disease (NASDAQ:CCXI)Presented at: 79th Annual Scientific Meeting of the American College of GastroenterologyOctober 17–22; 2015Philadelphia, USA
   Google Scholar
• WendtEKeshavSCCR9 antagonism: potential in the treatment of inflammatory bowel diseaseClin Exp Gastroenterol2015811913025897254
   PubMed Web of Science ®Google Scholar
• ChemoCentryx, IncChemoCentryx’s orally administered CCR9 inhibitor, CCX507, shown to be well tolerated and effective in CCR9 blockade in Phase I study (NASDAQ:CCXI)Presented at: 79th Annual Scientific Meeting of the American College of GastroenterologyOctober 21; 2014Philadelphia, USA
   Google Scholar
• BL-7040 Overview Inflammatory Bowel Disease2015JerusalemBioLineRx Ltd Available from: http://www.biolinerx.com/default.asp?pageid=13&itemid=23Accessed March 10, 2015
   Google Scholar
• GisbertJPArredondoMChaparroMDrug survival and reasons for discontinuation of anti-TNF therapy in inflammatory bowel disease (IBD) in clinical practiceJ Crohns Colitis20148S27
   Web of Science ®Google Scholar
• ThorlundKDruytsEMillsEJFedorakRNMarshallJKAdalimumab versus infliximab for the treatment of moderate to severe ulcerative colitis in adult patients naive to anti-TNF therapy: an indirect treatment comparison meta-analysisJ Crohns Colitis20148757158124491514
   PubMed Web of Science ®Google Scholar
• P408Differences in biologic efficacy and dose-escalation among anti-TNF agents in Crohn’s disease and ulcerative colitisJ Crohns Colitis20159Suppl 1S283
   Google Scholar
• RutgeertsMFSéverineVPaulCertolizumab pegol in the treatment of Crohn’s diseaseExpert Opin Biol Ther201313459560523451881
   PubMed Web of Science ®Google Scholar
• SinghSGargSKPardiDSWangZMuradMHLoftusEVJrComparative efficacy of biologic therapy in biologic-naive patients with Crohn disease: a systematic review and network meta-analysisMayo Clin Proc201489121621163525441399
   PubMed Web of Science ®Google Scholar
• BohmMEl ChaficAHFischerMGolimumab rescue for active Crohn’s disease refractory to other therapiesAm J Gastroenterol2014109S514S515
   Web of Science ®Google Scholar
• RutgeertsPSandbornWJFedorakRNOnercept for moderate-to-severe Crohn’s disease: a randomized, double-blind, placebo-controlled trialClin Gastroenterol Hepatol20064788889316797249
   PubMed Web of Science ®Google Scholar
• MozaffariSNikfarSAbdolghaffariAHAbdollahiMNew biologic therapeutics for ulcerative colitis and Crohn’s diseaseExpert Opin Biol Ther201414558360024502344
   PubMed Web of Science ®Google Scholar
• SandbornWJHanauerSBKatzSEtanercept for active Crohn’s disease: a randomized, double-blind, placebo-controlled trialGastroenterology200112151088109411677200
   PubMed Web of Science ®Google Scholar
• Neovacs presents successful results of Crohn’s disease drug trial at European Crohn’s & Colitis Congress [webpage on the Internet] Drugs.com; 2011 [cited February 2011]. Available from: http://www.drugs.com/clinical_trials/neovacs-presents-successful-results-crohn-s-trial-european-crohn-s-amp-colitis-congress-11235.htmlAccessed January 21, 2016
   Google Scholar
• De SanctisJBMijaresMSuárezACompagnoneRGarmendiaJMorenoDPharmacological properties of thalidomide and its analoguesRecent Pat Inflamm Allergy Drug Discov20104214414820307255
   PubMedGoogle Scholar
• QianJLiYSu1235 efficacy and safety of thalidomide in chinese patients with refractory Crohn’s diseaseGastroenterology1445S435
   Google Scholar
• FelipezLMGokhaleRTierneyMPKirschnerBSThalidomide use and outcomes in pediatric patients with Crohn disease refractory to infliximab and adalimumabJ Pediatr Gastroenterol Nutr2011541283321681114
   PubMed Web of Science ®Google Scholar
• GerichMEYoonJLTarganSRIppolitiAFVasiliauskasEALong-term outcomes of thalidomide in refractory Crohn’s diseaseAliment Pharmacol Ther201441542943725511905
   PubMed Web of Science ®Google Scholar
• TangJGaoXZhiMP436 Intravenous cyclophosphamide combined with thalidomide has a promising effect in refractory Crohn’s diseaseJ Crohns Colitis20148Suppl 1S247S248
   Web of Science ®Google Scholar
• FakhouryMCoussa-CharleyMAl-SalamiHAnti-inflammatory potential of artificial microcapsules containing thalidomide for use in treating Crohn’s diseaseJ Drug Deliv Therap2013351117
   Google Scholar
• BankheadCACG: Mixed Results With Biologic for Crohn’s2010 Available from: http://www.medpagetoday.com/MeetingCoverage/ACG/22913Accessed March 15, 2015
   Google Scholar
• SandsBEJacobsonEWSylwestrowiczTRandomized, double-blind, placebo-controlled trial of the oral IL-12/23 inhibitor apilimod mesylate for treatment of active Crohn’s diseaseInflamm Bowel Dis20091671209121819918967
   PubMed Web of Science ®Google Scholar
• SettesoldiACoppolaMRogaiFAnneseVUstekinumab: moving the target from psoriasis to Crohn’s diseaseExpert Rev Gastroenterol Hepatol20148151324410468
   PubMed Web of Science ®Google Scholar
• DOP029Ustekinumab efficacy and safety in Crohn’s disease patients refractory to conventional and anti-TNF therapy: a multicenter retrospective experienceJ Crohns Colitis20159Suppl 1S37S39
   Google Scholar
• P368Ustekinumab in super-refractory Crohn’s disease patientsJ Crohns and Colitis20159Suppl 1S262S263
   Google Scholar
• GoldhillJAdvances in Drug Discovery: Promising Crohn Disease Data Presented at ECCO for the IL-23 mAB, MEDI2070/AMG-1392015 Available from: http://leaddiscovery.blogspot.ro/2015/02/updatesplus-ibd-alert-promising-crohn.htmlAccessed March 5, 2015
   Google Scholar
• OP025A randomized, double-blind placebo-controlled phase 2a induction study of MEDI2070 (anti-p19 antibody) in patients with active Crohn’s disease who have failed anti-TNF antibody therapyJ Crohns Colitis20159Suppl 1S15S16
   Google Scholar
• ItoHTakazoeMFukudaYA pilot randomized trial of a human anti- IL-6 receptor monoclonal antibody in active Crohn’s diseaseGastroenterology20041264989996 discussion 94715057738
   PubMed Web of Science ®Google Scholar
• Pfizer’s Immunology Pipeline Has Few Bright Spots Besides Xeljanz2015 Available from: http://seekingalpha.com/article/2778925-pfizers-immunology-pipeline-has-few-bright-spots-besides-xeljanzAccessed March 15, 2015
   Google Scholar
• Adis InsightA multi-center, randomized, double-blind, active controlled study to assess efficacy, safety and tolerability of the anti-IL13 monoclonal antibody QAX576 in the treatment of perianal fistulas in patients suffering from Crohn’s disease Available from: http://adisinsight.springer.com/trials/700196337Accessed January 21, 2016
   Google Scholar
• SchmidBOP011. Tralokinumab (CAT-354), an interleukin 13 antibody, in moderate to severe ulcerative colitis: a phase 2 randomized placebo-controlled studyPaper presented at: 9th ECCO CongressFebuary 20–22, 2014Copenhagen
   Google Scholar
• FernerCUnited European Gastroenterology: document detailUnited European Gastroenterol J20131Suppl 1A79
   Google Scholar
• PanésJSuCBushmakinAGCappelleriJCMamoloCHealeyPRandomized trial of tofacitinib in active ulcerative colitis: analysis of efficacy based on patient-reported outcomesBMC Gastroenterol20151511425651782
   PubMed Web of Science ®Google Scholar
• SandbornWJGhoshSPanesJVranicIWangWNiezychowskiWA phase 2 study of tofacitinib, an oral Janus kinase inhibitor, in patients with Crohn’s diseaseClin Gastroenterol Hepatol201412914851493.e148224480677
   PubMed Web of Science ®Google Scholar
• BuchertMBurnsCJErnstMTargeting JAK kinase in solid tumors: emerging opportunities and challengesOncogene2015
   Web of Science ®Google Scholar
• D’HaensGSandbornWJColombelJFA phase II study of laquinimod in Crohn’s diseaseGut20156481227123525281416
   PubMed Web of Science ®Google Scholar
• MonteleoneGCarusoRPalloneFRole of Smad7 in inflammatory bowel diseasesWorld J Gastroenterol201218405664566823155305
   PubMed Web of Science ®Google Scholar
• KnyazevOVParfenovAIShcherbakovPLRuchkinaINKonoplyannikovAGCell therapy of refractory Crohn’s diseaseBull Exp Biol Med2013156113914524319711
   PubMed Web of Science ®Google Scholar
• RicartJPIngridOElenaRStem cell treatment for Crohn’s diseaseExp Rev Clin Immunol20146597605
   Google Scholar
• BurtRKCraigRMMilanettiFAutologous nonmyeloablative hematopoietic stem cell transplantation in patients with severe anti-TNF refractory Crohn disease: long-term follow-upBlood2010116266123613220837778
   PubMed Web of Science ®Google Scholar
• Al-tomaANijeboerPBoumaGVisserOMulderCJHematopoietic stem cell transplantation for non-malignant gastrointestinal diseasesWorld J Gastroenterol20142046173681737525516648
   PubMed Web of Science ®Google Scholar
• CCFA: A Phase I Study Evaluating Autologous Bone Marrow Derived Mesenchymal Stromal for Crohn’s Disease2015 Available from: http://www.ccfa.org/research/participate-in-research/find-studies-and-clinical-trials/emory-msc/emory-msc-1.html?referrer=https://www.google.ro/Accessed February 15, 2015
   Google Scholar
• MayerLPandakWMMelmedGYSafety and tolerability of human placenta-derived cells (PDA001) in treatment-resistant crohn’s disease: a phase 1 studyInflamm Bowel Dis201319475476023429460
   PubMed Web of Science ®Google Scholar
• Jauregui-AmezagaACabezónRRamírez-MorrosAIntraperitoneal administration of autologous tolerogenic dendritic cells for refractory Crohn’s disease: a Phase I studyJ Crohns Colitis20159121071107826303633
   PubMed Web of Science ®Google Scholar
• TaghipourNAghdaeiHAHaghighiAMossafaNTabaeiSJRostami-NejadMPotential treatment of inflammatory bowel disease: a review of helminths therapyGastroenterol Hepatol Bed Bench20147191625436093
   PubMedGoogle Scholar
• RothLMacDonaldJKMcDonaldJWChandeNSargramostim (GM-CSF) for induction of remission in Crohn’s disease: a cochrane inflammatory bowel disease and functional bowel disorders systematic review of randomized trialsInflamm Bowel Dis20121871333133922552871
   PubMed Web of Science ®Google Scholar
• ShahSTerdimanJGundlingKMahadevanUImmunoglobulin therapy for refractory Crohn’s diseaseTherap Adv Gastroenterol20147299102
   Web of Science ®Google Scholar