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Article ; Online: Modifying T-cell trafficking to the intestinal as a potential management for inflammatory bowel disease.

Lawrance, Ian Craig

2012 Volume 21, Issue 7, Page(s) 975–984

Abstract: Introduction: The Inflammatory Bowel Diseases (IBDs) are life-long chronic relapsing incurable inflammatory conditions that usually appear in the first few decades of life. There have been marked advances in the management of these conditions, but none ... ...

Abstract	Introduction: The Inflammatory Bowel Diseases (IBDs) are life-long chronic relapsing incurable inflammatory conditions that usually appear in the first few decades of life. There have been marked advances in the management of these conditions, but none of the currently available therapies are a panacea as they are neither universally efficacious nor will their efficacy necessarily last. There is a desperate need for new therapies that target the immunological deficits within the immune system with low side effects and long-term efficacy. Areas covered: Leukocyte trafficking into the intestinal mucosa is central to the inflammatory pathogenesis in both Crohn's disease (CD) and ulcerative colitis (UC) and modification of this trafficking has the ability to reduce the level of inflammation. The α4β7 integrin heterodimer is highly expressed on the CD4(+)CD45RA-memory T-cell subpopulation located within the intestine, and these play a critical part in the pathogenesis of IBD. Expert opinion: By modifying the integrin and chemokine interactions with their specific receptors, inhibition of α4(+) and α4β7(+) T-cell trafficking to the sites of intestinal inflammation is possible with promising outcomes in the management of IBD.
MeSH term(s)	Animals ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal/therapeutic use ; CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/immunology ; Cell Movement/drug effects ; Cell Movement/immunology ; Clinical Trials as Topic ; Humans ; Immunity, Mucosal/drug effects ; Inflammatory Bowel Diseases/drug therapy ; Inflammatory Bowel Diseases/etiology ; Inflammatory Bowel Diseases/immunology ; Integrins/antagonists & inhibitors ; Integrins/biosynthesis ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/immunology ; T-Lymphocyte Subsets/drug effects ; T-Lymphocyte Subsets/immunology ; Treatment Outcome
Chemical Substances	Antibodies, Monoclonal ; Integrins ; integrin alpha4beta7
Language	English
Publishing date	2012-07
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1182884-5
ISSN	1744-7658 ; 0967-8298 ; 1354-3784
ISSN (online)	1744-7658
ISSN	0967-8298 ; 1354-3784
DOI	10.1517/13543784.2012.690030
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Article ; Online: Novel topical therapies for distal colitis.

Lawrance, Ian Craig

World journal of gastrointestinal pharmacology and therapeutics

2011 Volume 1, Issue 5, Page(s) 87–93

Abstract: Distal colitis (DC) can be effectively treated with topical 5ASA agents. Suppositories target the rectum while enemas can reliably reach the splenic flexure. Used in combination with oral 5ASAs, the control of the inflammation is even more effective. ... ...

Abstract	Distal colitis (DC) can be effectively treated with topical 5ASA agents. Suppositories target the rectum while enemas can reliably reach the splenic flexure. Used in combination with oral 5ASAs, the control of the inflammation is even more effective. Unfortunately, resistant DC does occur and can be extremely challenging to manage. In these patients, the use of steroids, immunosuppressants and the anti-tumor necrosis factor α agents are often required. These, however, can be associated with systemic side effects and are not always effective. The investigation of new topical therapeutic agents is thus required as they are rarely associated with significant blood drug levels and side effects are infrequent. Some of the agents that have been proposed for use in resistant distal colitis include butyrate, cyclosporine and nicotine enemas as well as tacrolimus suppositories and tacrolimus, ecabet sodium, arsenic, lidocaine, rebamipide and Ridogrel(®) enemas. Some of these agents have demonstrated impressive results but the majority of the agents have only been assessed in small open-labelled patient cohorts. Further work is thus required with the investigation of promising agents in the context of randomized double-blinded placebo controlled trials. This review aims to highlight those potentially effective therapies in the management of resistant distal colitis and to promote interest in furthering their investigation.
Language	English
Publishing date	2011-04-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2583480-0
ISSN	2150-5349 ; 2150-5349
ISSN (online)	2150-5349
ISSN	2150-5349
DOI	10.4292/wjgpt.v1.i5.87
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Article ; Online: Topical agents for idiopathic distal colitis and proctitis.

Lawrance, Ian Craig

Journal of gastroenterology and hepatology

2011 Volume 26, Issue 1, Page(s) 36–43

Abstract: Rectally administered topical agents have demonstrated efficacy in the maintenance of distal colitis (DC) and proctitis and as they are rarely associated with significant blood drug levels, side effects are infrequent. The topical 5-aminosalicylic acid ( ... ...

Abstract	Rectally administered topical agents have demonstrated efficacy in the maintenance of distal colitis (DC) and proctitis and as they are rarely associated with significant blood drug levels, side effects are infrequent. The topical 5-aminosalicylic acid (5-ASA) suppositories and enemas target different regions of the distal colon and are effective for proctitis and DC, respectively. They demonstrate clinical results that are better than oral 5-ASAs and are preferred to topical steroids with better clinical, endoscopic and histological outcomes, without the risk of adrenal suppression. Disease resistant to topical agents, however, can be extremely difficult to manage. The addition of oral 5ASAs, steroids, immunosuppressants and the anti-tumor necrosis factor-α agents may be effective, but can result in significant side effects and not all patients will respond to the therapies. It is for these patients that new and novel therapies are required. Novel topical agents have been proposed for the management of resistant DC. These agents included butyrate, cyclosporine, and nicotine enemas, as well as tacrolimus suppositories, and tacrolimus, ecabet sodium, arsenic, lidocaine, bismuth, rebamipide and thromboxane enemas. While some of these agents appear to demonstrate impressive outcomes, the majority have only been examined in small open-labeled studies. There is thus a desperate need for more randomized double-blinded placebo controlled studies to investigate the clinical utility of these topical therapies. This review summarizes the efficacy of the established topical therapies, and explores the available data on the new and novel topical agents for the management of DC and proctitis.
MeSH term(s)	Administration, Rectal ; Administration, Topical ; Anti-Inflammatory Agents/administration & dosage ; Anti-Inflammatory Agents/adverse effects ; Colitis/drug therapy ; Enema ; Evidence-Based Medicine ; Gastrointestinal Agents/administration & dosage ; Gastrointestinal Agents/adverse effects ; Humans ; Proctitis/drug therapy ; Suppositories ; Treatment Outcome
Chemical Substances	Anti-Inflammatory Agents ; Gastrointestinal Agents ; Suppositories
Language	English
Publishing date	2011-01
Publishing country	Australia
Document type	Journal Article ; Review
ZDB-ID	632882-9
ISSN	1440-1746 ; 0815-9319
ISSN (online)	1440-1746
ISSN	0815-9319
DOI	10.1111/j.1440-1746.2010.06497.x
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Article ; Online: Novel topical therapies for distal colitis

Ian Craig Lawrance

World Journal of Gastrointestinal Pharmacology and Therapeutics, Vol 1, Iss 5, Pp 87-

2010 Volume 93

Abstract	Distal colitis (DC) can be effectively treated with topical 5ASA agents. Suppositories target the rectum while enemas can reliably reach the splenic flexure. Used in combination with oral 5ASAs, the control of the inflammation is even more effective. Unfortunately, resistant DC does occur and can be extremely challenging to manage. In these patients, the use of steroids, immunosuppressants and the anti-tumor necrosis factor α agents are often required. These, however, can be associated with systemic side effects and are not always effective. The investigation of new topical therapeutic agents is thus required as they are rarely associated with significant blood drug levels and side effects are infrequent. Some of the agents that have been proposed for use in resistant distal colitis include butyrate, cyclosporine and nicotine enemas as well as tacrolimus suppositories and tacrolimus, ecabet sodium, arsenic, lidocaine, rebamipide and Ridogrel® enemas. Some of these agents have demonstrated impressive results but the majority of the agents have only been assessed in small open-labelled patient cohorts. Further work is thus required with the investigation of promising agents in the context of randomized double-blinded placebo controlled trials. This review aims to highlight those potentially effective therapies in the management of resistant distal colitis and to promote interest in furthering their investigation.
Keywords	Resistant proctitis ; Tacrolimus ; Treatment ; Topical ; Diseases of the digestive system. Gastroenterology ; RC799-869 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Gastroenterology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences ; Therapeutics. Pharmacology ; RM1-950 ; DOAJ:Therapeutics
Language	English
Publishing date	2010-10-01T00:00:00Z
Publisher	Baishideng Publishing
Document type	Article ; Online
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Article: Infliximab in the management of the extra-intestinal manifestations of Crohn's disease.

Lawrance, Ian Craig

Journal of gastroenterology and hepatology

2004 Volume 19, Issue 11, Page(s) 1332–1333

MeSH term(s)	Adult ; Antibodies, Monoclonal/therapeutic use ; Crohn Disease/complications ; Crohn Disease/drug therapy ; Crohn Disease/pathology ; Female ; Gastrointestinal Agents/therapeutic use ; Humans ; Infliximab ; Male
Chemical Substances	Antibodies, Monoclonal ; Gastrointestinal Agents ; Infliximab (B72HH48FLU)
Language	English
Publishing date	2004-11
Publishing country	Australia
Document type	Case Reports ; Letter
ZDB-ID	632882-9
ISSN	0815-9319
ISSN	0815-9319
DOI	10.1111/j.1440-1746.2004.03551.x
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Article: Vitamin D metabolites are lower with active Crohn's disease and spontaneously recover with development of remission.

Haifer, Craig / Lawrance, Ian C / Center, Jacqueline R / Clarke, Michael W / Hart, Prue H / Eisman, John A / Lucas, Robyn / Ghaly, Simon

Therapeutic advances in gastroenterology

2019 Volume 12, Page(s) 1756284819865144

Abstract: Background: Vitamin D deficiency is associated with active Crohn's disease (CD). However, it remains unclear if lower 25-hydroxyvitamin D [25(OH)D] concentration is the cause, or consequence, of intestinal inflammation. Existing literature has focused ... ...

Abstract	Background: Vitamin D deficiency is associated with active Crohn's disease (CD). However, it remains unclear if lower 25-hydroxyvitamin D [25(OH)D] concentration is the cause, or consequence, of intestinal inflammation. Existing literature has focused on circulating 25(OH)D rather than the active metabolite 1,25(OH) Methods: Fifty-four patients with CD and not on corticosteroids or vitamin D supplements, were enrolled in a 6-month prospective cohort study. Sera were collected on enrolment and at 6 months and tested for 25(OH)D, 1,25(OH) Results: There were no differences in 25(OH)D or 1,25(OH) Conclusion: Levels of 24,25(OH)
Language	English
Publishing date	2019-07-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2440710-0
ISSN	1756-2848 ; 1756-283X
ISSN (online)	1756-2848
ISSN	1756-283X
DOI	10.1177/1756284819865144
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Article ; Online: Use of mycophenolate mofetil in inflammatory bowel disease.

Tan, Terrence / Lawrance, Ian Craig

World journal of gastroenterology

2009 Volume 15, Issue 13, Page(s) 1594–1599

Abstract: Aim: To assess the efficacy and safety of mycophenolate mofetil (MMF) prospectively in inflammatory bowel disease (IBD) patients intolerant or refractory to conventional medical therapy.: Methods: Crohn's disease (CD) or ulcerative colitis/IBD ... ...

Abstract	Aim: To assess the efficacy and safety of mycophenolate mofetil (MMF) prospectively in inflammatory bowel disease (IBD) patients intolerant or refractory to conventional medical therapy. Methods: Crohn's disease (CD) or ulcerative colitis/IBD unclassified (UC/IBDU) patients intolerant or refractory to conventional medical therapy received MMF (500-2000 mg bid). Clinical response was assessed by the Harvey Bradshaw index (HBI) or colitis activity index (CAI) after 2, 6 and 12 mo of therapy, as were steroid usage and adverse effects. Results: Fourteen patients (9 CD/5 UC/IBDU; 8M/6F; mean age 50.4 years, range 28-67 years) were treated and prospectively assessed for their response to oral MMF. Of the 11 patients who were not in remission on commencing MMF, 7/11 (63.6%) achieved remission by 8 wk. All 3 patients in remission on commencing MMF maintained their remission. Ten patients were still on MMF at 6 mo with 9/14 (64.3%) in remission, while of 12 patients followed for 12 mo, 8 were in remission without dose escalation (66.7%). Three patients were withdrawn from the MMF due to drug intolerance. There were no serious adverse events attributed due to the medication. Conclusion: MMF demonstrated efficacy in the management of difficult IBD. MMF appeared safe, well tolerated and efficacious for both short and long-term therapy, without the need for dose escalation. Further evaluation of MMF comparing it to conventional immunosuppressants is required.
MeSH term(s)	Adolescent ; Adult ; Aged ; Colitis, Ulcerative/drug therapy ; Crohn Disease/drug therapy ; Female ; Humans ; Immunosuppressive Agents/therapeutic use ; Inflammatory Bowel Diseases/drug therapy ; Male ; Middle Aged ; Mycophenolic Acid/analogs & derivatives ; Mycophenolic Acid/therapeutic use ; Young Adult
Chemical Substances	Immunosuppressive Agents ; Mycophenolic Acid (HU9DX48N0T)
Language	English
Publishing date	2009-04-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	2185929-2
ISSN	2219-2840 ; 1007-9327
ISSN (online)	2219-2840
ISSN	1007-9327
DOI	10.3748/wjg.15.1594
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Article ; Online: Stevens-Johnson syndrome complicating adalimumab therapy in Crohn's disease.

Salama, Muna / Lawrance, Ian-Craig

World journal of gastroenterology

2009 Volume 15, Issue 35, Page(s) 4449–4452

Abstract: The anti-tumor necrosis factor (TNF)alpha medications demonstrate efficacy in the induction of remission and its maintenance in numerous chronic inflammatory conditions. With the increasing number of patients receiving anti-TNFalpha agents, however, less ...

Abstract	The anti-tumor necrosis factor (TNF)alpha medications demonstrate efficacy in the induction of remission and its maintenance in numerous chronic inflammatory conditions. With the increasing number of patients receiving anti-TNFalpha agents, however, less common adverse reactions will occur. Cutaneous eruptions complicating treatment with an anti-TNFalpha agent are not uncommon, occurring in around 20% of patients. Adalimumab, a fully humanized antibody against TNFalpha, may be expected to cause minimal immune-mediated skin reactions compared to the chimeric monoclonal antibody, infliximab. We, however, report a case of Stevens-Johnson syndrome that required hospitalization and cessation of adalimumab in a patient with Crohn's disease (CD). In this case report, a 29-year-old male with colonic and perianal CD with associated erythema nodosum and large joint arthropathy developed severe mucositis, peripheral rash and desquamation, fevers and respiratory symptoms concomitant with a second dose of 40 mg adalimumab after a 2 mo break from adalimumab therapy. Skin biopsies of the abdominal wall confirmed erythema multiforme and the patient was on no other drugs and infective etiologies were excluded. The patient responded rapidly to IV hydrocortisone and was able to be commenced on infliximab without recurrence of the Stevens-Johnson syndrome. Desquamating skin reactions have now been described in three of the TNFalpha antagonists (infliximab, etanercept and adalimumab). These reactions can be serious and prescribers need to be aware of the potential mucocutaneous side effects of these agents, especially as Stevens-Johnson syndrome is associated with significant morbidity and mortality.
MeSH term(s)	Adalimumab ; Adult ; Anti-Inflammatory Agents/adverse effects ; Anti-Inflammatory Agents/therapeutic use ; Antibodies, Monoclonal/adverse effects ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized ; Crohn Disease/drug therapy ; Humans ; Male ; Stevens-Johnson Syndrome/chemically induced ; Stevens-Johnson Syndrome/therapy ; Treatment Outcome ; Tumor Necrosis Factor-alpha/adverse effects ; Tumor Necrosis Factor-alpha/antagonists & inhibitors
Chemical Substances	Anti-Inflammatory Agents ; Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Tumor Necrosis Factor-alpha ; Adalimumab (FYS6T7F842)
Language	English
Publishing date	2009-09-17
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2185929-2
ISSN	2219-2840 ; 1007-9327
ISSN (online)	2219-2840
ISSN	1007-9327
DOI	10.3748/wjg.15.4449
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Article ; Online: Use of infliximab in the prevention and delay of colectomy in severe steroid dependant and refractory ulcerative colitis.

Willert, Robert P / Lawrance, Ian Craig

World journal of gastroenterology

2008 Volume 14, Issue 16, Page(s) 2544–2549

Abstract: Aim: To determine if infliximab can prevent or delay surgery in refractory ulcerative colitis (UC).: Methods: UC patients who failed to have their disease controlled with conventional therapies and were to undergo colectomy if infliximab failed to ... ...

Abstract	Aim: To determine if infliximab can prevent or delay surgery in refractory ulcerative colitis (UC). Methods: UC patients who failed to have their disease controlled with conventional therapies and were to undergo colectomy if infliximab failed to induce a clinical improvement were reviewed. Patients were primarily treated with a single 5 mg/kg infliximab dose. The Colitis Activity Index (CAI) was used to determine response and remission. Data of 8 wk response and colectomy rates at 6 mo and 12 mo were collected. Results: Fifteen patients were included, 7 with UC unresponsive or intolerant to i.v. hydrocortisone, and 8 with active disease despite oral steroids (all but one with therapeutic dosage and duration of immunomodulation). All the i.v. hydrocortisone-resistant/intolerant patients had been on azathioprine/6-MP < 8 wk. At 8 wk, infliximab induced a response in 86.7% (13/15) with 40% in remission (6/15). Within 6 mo of treatment 26.7% (4/15) had undergone colectomy and surgery was avoided in 46.6% (7/15) at 12 mo. The colectomy rate at 12 mo in those on immunomodulatory therapy < 8 wk at time of infliximab was 12.5% (1/8) compared with 100% (7/7) in patients who were on long-term maintenance immunomodulators (P < 0.02). Conclusion: Infliximab prevented colectomy due to active disease in immunomodulatory-naive, refractory UC patients comparable to the use of Cyclosporine. In patients, however, on effective dosage and duration of immunomodulation at time of infliximab therapy colectomy was not avoided.
MeSH term(s)	Adolescent ; Adult ; Age of Onset ; Antibodies, Monoclonal/therapeutic use ; Azathioprine/therapeutic use ; Colectomy/statistics & numerical data ; Colitis, Ulcerative/drug therapy ; Colitis, Ulcerative/surgery ; Follow-Up Studies ; Gastrointestinal Agents/therapeutic use ; Humans ; Hydrocortisone/therapeutic use ; Infliximab ; Middle Aged ; Treatment Failure ; Treatment Outcome ; Young Adult
Chemical Substances	Antibodies, Monoclonal ; Gastrointestinal Agents ; Infliximab (B72HH48FLU) ; Azathioprine (MRK240IY2L) ; Hydrocortisone (WI4X0X7BPJ)
Language	English
Publishing date	2008-04-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	2185929-2
ISSN	2219-2840 ; 1007-9327
ISSN (online)	2219-2840
ISSN	1007-9327
DOI	10.3748/wjg.14.2544
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Article ; Online: Mesenchymal cell proliferation and programmed cell death: key players in fibrogenesis and new targets for therapeutic intervention.

Luna, Jeroni / Masamunt, Maria Carme / Lawrance, Ian Craig / Sans, Miquel

American journal of physiology. Gastrointestinal and liver physiology

2011 Volume 300, Issue 5, Page(s) G703–8

Abstract: An exquisite equilibrium between cell proliferation and programmed cell death is required to maintain physiological homeostasis. In inflammatory bowel disease, and especially in Crohn's disease, enhanced proliferation along with defective apoptosis of ... ...

Abstract	An exquisite equilibrium between cell proliferation and programmed cell death is required to maintain physiological homeostasis. In inflammatory bowel disease, and especially in Crohn's disease, enhanced proliferation along with defective apoptosis of immune cells are considered key elements of pathogenesis. Despite the relatively limited attention that has been given to research efforts devoted to intestinal fibrosis to date, there is evidence suggesting that enhanced proliferation along with defective programmed cell death of mesenchymal cells can significantly contribute to the development of excessive fibrogenesis in many different tissues. Moreover, some therapies have demonstrated potential antifibrogenic efficacy through the regulation of mesenchymal cell proliferation and programmed cell death. Further understanding of the pathways involved in the regulation of mesenchymal cell proliferation and apoptosis is, however, required.
MeSH term(s)	Animals ; Apoptosis/physiology ; Cell Proliferation ; Crohn Disease/pathology ; Fibrosis/pathology ; Humans ; Inflammatory Bowel Diseases/pathology ; Mesenchymal Stromal Cells/physiology
Language	English
Publishing date	2011-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	603840-2
ISSN	1522-1547 ; 0193-1857
ISSN (online)	1522-1547
ISSN	0193-1857
DOI	10.1152/ajpgi.00504.2010
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