Cancer Treatment Today » Gastrointestinal Diseases

Does measuring antibodies to infliximab help?

M Levin, MD — Fri, 03 Jan 2014 01:07:36 +0000

Antibodies to infliximab (ATIs) have been associated with loss of clinical response and lower serum infliximab (IFX) levels in some studies of patients with inflammatory bowel disease (IBD). Presumable lower levels mean less effectiveness, but it needs to be proven. It may be clinically useful to be able to assess and predict diminishing response. A recent meta-analysis of all available studies concluded that the presence of ATIs is associated with a significantly higher risk of loss of clinical response to IFX and lower serum IFX levels in patients with IBD. However, most studies were flawed in that published studies on this topic lack uniform reporting of outcomes and high risk of bias was present in all the included studies. This means that the method of metanalysis may not be accurate in pooling all studies and obtaining a meaningful result.

Similar conclusions are reached by reviews that look at this question. For example, a recent paper outlines why antibodies to infliximab (ATI) cannot be used as a surrogate marker for immunogenicity, or to predict clinical outcome or safety. This is because up to half of patients still need dose adjustment for recurrent symptoms and 20% of patients lose response, even when treatment is optimised to avoid ATI through scheduled maintenance therapy or concomitant immunomodulators

Measurement of serum antibodies to infliximab has not received clearance by the FDA and there is not sufficient peer-reviewed scientific literature that demonstrates that the procedure is effective.

See Professional version here

Antibodies to inflixumab

M Levin, MD — Thu, 26 Dec 2013 16:17:57 +0000

Antibodies to infliximab (ATIs) have been associated with loss of clinical response and lower serum infliximab (IFX) levels in some studies of patients with inflammatory bowel disease (IBD). Lower drug levels can mean less effect ont eh disease. It is clinically useful to be able to assess and predict diminishing response. A recent meta-analysis concluded that the presence of ATIs is associated with a significantly higher risk of loss of clinical response to IFX and lower serum IFX levels in patients with IBD. However, most studies were flawed in that published studies on this topic lack uniform reporting of outcomes and high risk of bias was present in all the included studies.

Similar conclusions are reached by reviews that look at this question and are likewise limited in the same way. For example, a recent paper outlines why antibodies to infliximab (ATI) cannot be used as a surrogate marker for immunogenicity,
or to predict clinical outcome or safety. This is because up to half of patients still need dose adjustment for recurrent symptoms and 20% of patients lose response, even when treatment is optimised to avoid ATI through scheduled maintenance therapy or concomitant immunomodulators. The effects of ATI is, therefore, diluted statistically in these studies.

Thus far many questions persist about how useful ATI testing can be. Measurement of serum antibodies to infliximab has not received clearance by the FDA andthere is not sufficient peer-reviewed scientific literature that demonstrates that the procedure is effective.

For Professional version see here

Atelvia and gastrointestinal toxicity – pro

M Levin, MD — Thu, 25 Apr 2013 14:02:03 +0000

Risedronic acid(Atelvia) is a bisphosphonate used to strengthen bone, treat or prevent osteoporosis, and treat Paget’s disease of bone. It is recommended that risedronate be taken with the body upright, and followed by a glass of water. Moreover, it is recommended that no food or drink other than water be taken for 2 hours before and 30 minutes after taking risedronate. Risedronate has a faster esophageal transit time and a different chemical chain which results in less gastrointestinal side-effects than other drugs in this class. The dosage instructionssay that risedronate can be taken with less water than other drugs in the class. It is taken weekly but risedronate is also available as a 75mg tablet to be taken on two consecutive days each month (2CDM) in order to optimize patient adherence. These factors may make it preferred for use in the elderly.

M.R McLung et al, Efficacy and safety of a novel delayed-release risedronate 35 mg once-a-week tablet. Osteoporos Int. 2012 January; 23(1): 267–276.

McClung MR, Balske A, Burgio DE, Wenderoth D, Recker RR.
Treatment of postmenopausal osteoporosis with delayed-release risedronate 35 mg weekly for 2 years.Osteoporos Int. 2013 Jan;24(1):301-10.

For Lay version see here

For more on Zometa in osteoporosis and for Forteo see here

Sandostatin for angiodysplasia and bleeding

M Levin, MD — Tue, 18 Dec 2012 22:43:01 +0000

Angiodysplasias are usually asymptomatic but they can cause of intestinal bleedingare a more common problem in the elderly. It is notoriously difficult to treat. A number of reports suggest that itcan help to decrease bleeding. There are no supportive guidelines to my knowledge a recent review concluded: “A significant number of patients with bleeding gastrointestinal angiodysplasia respond to treatment with octreotide by reducing the need for blood products. As all the included studies had small sample sizes, multicenter randomized trials are needed to confirm these findings. However, it seems reasonable to administer octreotide especially in patients with refractory bleeding, inaccessible lesions and in patients at high risk for other interventions.”

For Professional version see here

Octreotide in gastrointentinal angiodysplasia – pro

M Levin, MD — Tue, 18 Dec 2012 22:40:34 +0000

Angiodysplasias are usually asymptomatic but they can cause of GI bleeding in 3–6% of all patients and are a more common cause of beeeding in the elderly. It is notoriously difficult to treat. A number of reports suggest that it is a valuable adjunct in the treatment of gastro-inestinal dysplasia and can decrease bleeding. There are no supportive guidelines to my knowledge but the role of somatostatin analogues for refractory bleeding GI angiodysplasias has been systematically reviewed by Brown et al.
He concluded: “A significant number of patients with bleeding gastrointestinal angiodysplasia respond to treatment with octreotide by reducing the need for blood products. As all the included studies had small sample sizes, multicenter randomized trials are needed to confirm these findings. However, it seems reasonable to administer octreotide especially in patients with refractory bleeding, inaccessible lesions and in patients at high risk for other interventions.”.

Rivera M, Lucero J, Guerrero A, Márquez JL, Montes R, Suñer M, Ruiz A, Valdivia MA, Mateos J. Octreotide in the treatment of angiodysplasia in patients with advanced chronic renal failure.Nefrologia. 2005;25(3):332-5.

Junquera F, Saperas E, Videla S, et al. Long-term efficacy of octreotide in the prevention of recurrent bleeding from gastrointestinal angiodysplasia. Am J Gastroenterol 2007; 102:254.

Brown C, Subramanian V, Wilcox CM, Peter S. Somatostatin analogues in the treatment of recurrent bleeding from gastrointestinal vascular malformations: an overview and systematic review of prospective observational studies. Dig Dis Sci 2010; 55:2129.

Scaglione G, Pietrini L, Russo F, et al. Long-acting octreotide as rescue therapy in chronic bleeding from gastrointestinal angiodysplasia. Aliment Pharmacol Ther 2007; 26:935.

Molina-Infante J, Perez-Gallardo B. Somatostatin analogues for bleeding gastrointestinal angiodysplasias: when should thalidomide be prescribed?. Dig Dis Sci. Jan 2011;56(1):266-7.

Bon C, Aparicio T, Vincent M, et al. Long-acting somatostatin analogues decrease blood transfusion requirements in patients with refractory gastrointestinal bleeding associated with angiodysplasia. Aliment Pharmacol Ther 2012; 36:587.

For Lay version see here

For a discussion of thalidomide see here

Incivik

M Levin, MD — Thu, 09 Aug 2012 18:59:23 +0000

Telaprevir(Incivik) is the first hepatitis C drug that has demonstrated activity in patients who have failed prior therapy. In patients who received peginterferon alfa-2a and ribavirin for a year, the addition of telapravir for 24 weeks achieved a sustained virologic response(SVR) of 53% compared to 14% in patients who did not receive telapravir.It is thought that some patients who accomplish this outcome may be cured of Hepatitis, a feat rarely accomplished before. In a second randomized controlled trial (REALIZE) of patients who had previously relapsed or had only a partial response, rates of SVR were higher in patients treated with telaprevir (83% to 88%) compared to 24% in controls. In a third trial (ADVANCE) for previously untreated patients, patients taking telaprevir had a SVR (69% to 75%) versus 44% in the control group.

Read the Professional version here.

Primary Sclerosing Cholangitis (PSC)

M Levin, MD — Tue, 17 Jul 2012 14:33:49 +0000

Primary sclerosing cholangitis (PSC) is a chronic, liver disease characterized by bile stasis within bile ducts and liver inflammation and fibrosis. It is thought to be an immune mediated, progressive disorder that eventually develops into liver cirrhosis, portal hypertension and hepatic decompensation, in the majority of patients. How does one follow the activity of this disease? Guidelines do not recommend routine MRCP or ERCP to screen for screening for cholangio or hepatocellular(liver) carcinoma. They do recommend these tests for patients with deterioration in their constitutional performance or worsening liver tests. These patients should have these tests to evaluate for a possible chalangiocarcinoma.

Humira for Ulcerative Colitis

M Levin, MD — Wed, 20 Jun 2012 18:13:29 +0000

Adalimumab (Humira) is an anti-tumor necrosis factor (TNF) agent that is approved for both inducing and maintaining remission in moderately to severely active Crohn’s disease. Small open-label trials and case reports suggest that it can induce responses in both patients who had been treated with this class of drugs and those who had not been so treated, and anti-TNF-treated patients with active ulcerative colitis. This led to a phase III trial sponsored by the pharmaceutical company Abott. In it, of the 248 patients treated with 40mg every other week, 16.5 percent achieved clinical remission compared to 9.3 percent on placebo at week 8 p=0.019). At week 52, 17.3 percent achieved clinical remission compared to 8.5 percent on placebo (p=0.004). These results were statistically significant compared to placebo. The safety results was as expected and known from other studies of Humira.

On April 11, 2012 the European Commission has approved HUMIRA® (adalimumab) for the treatment of moderately to severely active ulcerative colitis (UC) in adult patients who have had an inadequate response to conventional therapy. In the USA, in May of 2012, Humira is approved for: Rheumatoid Arthritis, Juvenile Idiopathic Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Crohn’s Disease, Plaque Psoriasis but not for ulceratuve colitis.

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Routine MCP or ERCP Surveillance for Cholagniocarcinoma or Liver Cancer in Patients with Primary Biliary Cirrhosis.

M Levin, MD — Wed, 20 Jun 2012 22:09:44 +0000

Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver disease characterized by inflammation and fibrosis of both intrahepatic and extrahepatic bile ducts. It is thoughtto be an immune mediated, progressive disorder that eventually develops into cirrhosis, portal hypertension and hepatic decompensation, in the majority of patients. Guidelines do not recommend routine MRCP or ERCP to screen for chalngiocarcinoma or hepatocellular carcinoma. They do recommend that patients with deterioration in their constitutional performance status or liver biochemical-related parameters should undergo an evaluation for CCA.

Read the Professional version here.