- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Predictors of Placebo Response in Patients With Irritable Bowel Syndrome and Constipation: A Post-Hoc Analysis From Pooled Phase 2b/3 Studies Assessing the Safety and Efficacy of Linaclotide (Crown Ballroom) - Sep 4, 2022 - Abstract #ACG2022ACG_2519;
P2b, P3, P
T wo predictors of placebo response were identified as having the largest impact on the FDA abdominal pain responder endpoint. Higher baseline variation in abdominal pain was associated with higher placebo response (coefficient, standard error [SE]: 0.20, 0.068; P = .0032), and higher mean baseline abdominal pain was associated with lower placebo response (coefficient, SE: −0.15, 0.019; P Table ].
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Longstanding Proctocolitis Secondary to Chronic Inferior Mesenteric Vein (IMV) Occlusion (Crown Ballroom) - Sep 4, 2022 - Abstract #ACG2022ACG_2145;
Case Description/ A 43-year-old male with a past medical history of DM, HTN, renal transplant on immunosuppression, prothrombin gene mutation and DVT on apixaban initially presented with rectal pain and diarrhea of one month duration...He was started on linaclotide, mesalamine enemas, and hydrocortisone enemas...Early detection of IMVT can decrease both morbidity and mortality while effectively guiding therapy. Figure: A) Diffuse severe inflammation with mucosal friability and granularity of the descending colon B) Diffuse severe inflammation with mucosal friability and erosions in sigmoid colon C) Diffuse severe inflammation with congestion, friability, and shallow ulcerations in rectum with oozing
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Holy Cow! When Cecal “Polypectomy” Specimen Shows Cow’s Liver (Crown Ballroom) - Sep 4, 2022 - Abstract #ACG2022ACG_1890;
His constipation was well-controlled with linaclotide 72 mcg daily...Figure 1C: At higher power: sheets of polygonal cells with round, centrally located nuclei, and abundant eosinophilic cytoplasm compatible with hepatocytes. The hepatocytes arranged in plates extend from central vein to portal triad.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Trial completion: Efficacy of Family Constellations in the General Population (clinicaltrials.gov) - Aug 24, 2022
P=N/A, N=80, Completed,
IBS-C seriously affects the quality of life of patients with IBS-C, and linaclotide can improve symptoms and quality of life at less cost. Active, not recruiting --> Completed
- |||||||||| Clinical guideline: AGA Clinical Practice Guideline on the Pharmacological Management of Irritable Bowel Syndrome With Constipation. (Pubmed Central) - Jun 30, 2022
The panel made a strong recommendation for linaclotide (high certainty) and conditional recommendations for tenapanor, plecanatide, tegaserod, and lubiprostone (moderate certainty), polyethylene glycol laxatives, tricyclic antidepressants, and antispasmodics (low certainty). The panel made a conditional recommendation against the use of selective serotonin reuptake inhibitors (low certainty).
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Journal: Linaclotide utilization and potential for off-label use and misuse in three European countries. (Pubmed Central) - Jun 22, 2022
The proportions of linaclotide users considered at risk for potential off-label use for weight loss or as a laxative were 17.1%, 29.7%, and 1.7%, and the proportions of users considered at risk of misuse due to a history of MBO or IBD were 3.5%, 4.6%, and 5.7% in the United Kingdom, Spain, and Sweden, respectively. Potential linaclotide off-label use and misuse appears limited, as evidenced by the small sizes of the patient subgroups at risk for off-label use and misuse.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Enrollment open: Application of Linaclotide Capsule in Bowel Preparation for Colonoscopy (clinicaltrials.gov) - Jun 22, 2022
P=N/A, N=1300, Recruiting,
Potential linaclotide off-label use and misuse appears limited, as evidenced by the small sizes of the patient subgroups at risk for off-label use and misuse. Not yet recruiting --> Recruiting
- |||||||||| Review, Journal: Constipation in Cancer Patients - an Update of Clinical Evidence. (Pubmed Central) - Jun 11, 2022
Naldemedine, naloxegol, and methylnaltrexone are supported by quality evidence for OIC management. Naloxone or naltrexone, taken orally in combined formulations with opioids, may be valuable in preventing or reducing OIC symptoms.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Trial completion date, Trial primary completion date: Application of Linaclotide Capsule in Bowel Preparation for Colonoscopy (clinicaltrials.gov) - May 26, 2022
P=N/A, N=1300, Not yet recruiting,
No abstract available Trial completion date: Aug 2022 --> Feb 2023 | Trial primary completion date: Jul 2022 --> Dec 2022
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Enrollment change, Trial termination, Trial primary completion date: Assessment of Responsiveness to Treatment by Experience Sampling Method (clinicaltrials.gov) - May 25, 2022
P=N/A, N=16, Terminated,
IBS-C seriously affects the quality of life of patients with IBS-C, and linaclotide can improve symptoms and quality of life at less cost. N=30 --> 16 | Recruiting --> Terminated | Trial primary completion date: Jan 2022 --> May 2022; Slow inclusion rate.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Journal: IRBIT as a Regulator of Bicarbonate Transport in the Small Intestine. (Pubmed Central) - May 14, 2022
IRBIT is highly expressed in the duodenum and appears to functionally interact with SLC26A3. IRBIT may be an attractive target to modulate small intestinal pH in diseases like cystic fibrosis, where impaired bicarbonate secretion contributes to intestinal disease and malnutrition.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie, Trulance (plecanatide) / Bausch Health
Journal: GUCY2C-Enriched Intestinal Neuropod Cells Modulate Visceral Pain. (Pubmed Central) - May 14, 2022
They support a model in which GUCA2B sufficiency activates GUCY2C to suppress DRG neuron excitability, while GUCA2B insufficiency silences GUCY2C to produce DRG hyperexcitability and CVP. Finally, they suggest that linaclotide relieves CVP by stimulating GUCY2C neuropod cells to inhibit DRG excitability and nociceptive signaling.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie, Trulance (plecanatide) / Bausch Health
Trial completion date, Trial initiation date, Trial primary completion date: GCC Agonist Signal in the Small Intestine (clinicaltrials.gov) - May 12, 2022
P1, N=39, Not yet recruiting,
Finally, they suggest that linaclotide relieves CVP by stimulating GUCY2C neuropod cells to inhibit DRG excitability and nociceptive signaling. Trial completion date: Sep 2024 --> Feb 2025 | Initiation date: Apr 2022 --> Aug 2022 | Trial primary completion date: Sep 2024 --> Feb 2025
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
CHRONIC IDIOPATHIC CONSTIPATION SUFFERERS AND TREATMENT SATISFACTION: PRESCRIPTION VS. OVER-THE-COUNTER MEDICATIONS (Poster Hall - San Diego Convention Center) - Apr 25, 2022 - Abstract #DDW2022DDW_5935;
The most frequently reported Rx medication currently taken was linaclotide, at 29.1% (n=177)...CIC patients currently taking an Rx medication with or without concomitant use of OTC are more satisfied with the control of their symptoms than CIC patients currently taking an OTC only. There may be an opportunity for clinicians to improve CIC patient education and care.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
LINACLOTIDE INCREASES DUODENAL BICARBONATE SECRETION INDEPENDENT OF CFTR BY ALTERING APICAL MEMBRANE DYNAMICS OF DRA AND NHE3 (27 - San Diego Convention Center) - Apr 25, 2022 - Abstract #DDW2022DDW_5246;
Conclusion : Linaclotide stimulates duodenal bicarbonate secretion, even in the absence of CFTR, through increased membrane trafficking of DRA and decreased membrane expression of NHE3. These data provide further insights into the mechanisms of action of linaclotide, but also importantly, suggest that linaclotide may be a useful therapy for individuals with CF who experience impaired bicarbonate secretion.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
CHRONIC EFFECT OF LINACLOTIDE ON THE COMPOSITION AND FUNCTION OF GUT MICROBIOTA: POTENTIAL MECHANISMS FOR INHIBITION OF VISCERAL PAIN (28ABC - San Diego Convention Center) - Apr 25, 2022 - Abstract #DDW2022DDW_4133;
This was accompanied by altered microbiota in the colon which contributes to an upregulation of cGMP transporters and increased cGMP production in the epithelial cells and its transport into the submucosa space to exert its analgesic effect on the mesenteric sensory fibers. This provides a novel explanation for the analgesic effects of linaclotide on abdominal pain in IB-C patients.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
PATIENT-DERIVED MEANINGFUL CHANGE THRESHOLDS IN THE NOVEL ABDOMINAL SCORE OUTCOME MEASURE IN IRRITABLE BOWEL SYNDROME WITH CONSTIPATION (28ABC - San Diego Convention Center) - Apr 25, 2022 - Abstract #DDW2022DDW_2214;
P3
Abstract Body Introduction : Linaclotide (LIN) is a guanylate cyclase-C agonist approved for treating adult patients with chronic idiopathic constipation and irritable bowel syndrome with constipation (IBS-C)...An AS improvement of ~2.0 points correlated with any relief and adequate relief, while an AS improvement of ~2.5 points correlated with complete relief. These findings may help clinicians set clinical expectations based on clinical trial Results .
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Clinical, Journal: Polyethylene glycol combined with linaclotide is an effective and well-tolerated bowel preparation regimen for colonoscopy: an endoscopist-blinded, randomized, controlled trial. (Pubmed Central) - Apr 12, 2022
3JCI Insight,2018.4;3(19).Supported by Ironwood Pharmaceuticals Inc, Allergan plc (prior to acquisition by AbbVie, Inc), ARC and NHMRC Australia. Two liters of PEG combined with 290 µg linaclotide was an effective and well-tolerated bowel preparation regimen.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Trial completion date, Trial primary completion date: Efficacy of Linaclotide in Type II Diabetics With Chronic Constipation (clinicaltrials.gov) - Apr 11, 2022
P4, N=23, Active, not recruiting,
Two liters of PEG combined with 290 µg linaclotide was an effective and well-tolerated bowel preparation regimen. Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Oct 2021 --> Oct 2022
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Review, Journal: Guanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain. (Pubmed Central) - Apr 9, 2022
Due to the preponderance of evidence we focus on linaclotide, a 14-amino acid GC-C agonist with very low oral bioavailability that acts within the gut. Collectively, the weight of experimental and clinical evidence supports the concept that GC-C agonists act as peripherally acting visceral analgesics.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie
Clinical, P3 data, Journal: Efficacy and Safety of Linaclotide in Patients with Irritable Bowel Syndrome with Constipation: Chinese Sub-Cohort Analysis of a Phase III, Randomized, Double-Blind, Placebo-controlled Trial. (Pubmed Central) - Mar 8, 2022
P3
Additionally, we discuss the important features and studies for bisacodyl to understand its peculiar characteristics and guide its use in clinical practice, but also stimulate research on open questions. Linaclotide (290 μg/d) was efficacious and well-tolerated in Chinese IBS-C patients with a rapid onset of effect.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie, Amitiza (lubiprostone) / Takeda, Mallinckrodt
Review, Journal: Chronic constipation, gastroenterohepatologist`s approach. (Pubmed Central) - Mar 3, 2022
In case of failure, the use of lubiprostone is indicated, as well as linaclotide. Surgical treatment of constipation is reserved for cases of refractory constipation, with delayed intestinal transit.
- |||||||||| Linzess (linaclotide) / Astellas, Ironwood Pharma, AbbVie, Trulance (plecanatide) / Bausch Health
Journal: Guanylin and uroguanylin: a promising nexus in intestinal electrolyte and fluid homeostasis. (Pubmed Central) - Feb 22, 2022
Moreover, GC-C/cGMP signaling is involved in the regulation of intestinal barrier integrity, epithelial cell renewal, cell cycle, DNA damage repair, inflammatory responses, epithelial-mesenchymal transition and cancer progression. Impairment of GC-C activation causes functional gastrointestinal disorders, inflammatory bowel disease, visceral pain and colorectal cancer, suggesting that oral supplementation of guanyl peptide analogs (linaclotide, plecanatide) may prove useful for the treatment of these diseases.
- |||||||||| Xifaxan (rifaximin) / Alfa Wassermann, Bausch Health, Norgine, ASKA Pharma
Journal: Diarrhea-Predominant and Constipation-Predominant Irritable Bowel Syndrome: Current Prescription Drug Treatment Options. (Pubmed Central) - Feb 15, 2022
We performed a narrative review of the literature to summarize these important determinants of treatment choice including: labeled indications; clinical profiles of efficacy, safety, and tolerability of prescription drugs; and cost-effectiveness for diarrhea-predominant IBS drugs (IBS-D: alosetron, eluxadoline, and rifaximin) and constipation-predominant IBS drugs (IBS-C: linaclotide, lubiprostone, plecanatide, tegaserod, and tenapanor). We then review the standard model of shared decision-making aimed at guiding an informed, patient-centered discussion to integrate comparative clinical and cost outcomes toward choosing an IBS treatment in practice.
- |||||||||| Xifaxan (rifaximin) / Alfa Wassermann, Bausch Health, Norgine, ASKA Pharma
Review, Journal: Irritable bowel syndrome. (Pubmed Central) - Feb 3, 2022
The disease affects 5%-10% of healthy individuals at any given time and, in most people, has a relapsing-remitting course. This article reviews some of the main and most current evidence on its epidemiology, risk factors, pathophysiology, clinical manifestations, diagnostic approach, and therapeutic options, both dietary, pharmacological and psychotherapeutic.
- |||||||||| Xifaxan (rifaximin) / Alfa Wassermann, Bausch Health, Norgine, ASKA Pharma
Journal: The new guideline on irritable bowel syndrome: what is new? (Pubmed Central) - Jan 21, 2022
For abdominal pain/cramps, studies show good results for spasmolytics, especially peppermint oil, and for tricyclic-type antidepressants. For the main symptom of flatulence, probiotics, rifaximin and especially the low-FODMAP diet can show positive results in studies.
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