Cancer Treatment Today » Immunotherapy

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.

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Immunoglobulin for Gullain-Barre Syndrome

M Levin, MD — Sun, 14 Jul 2013 22:05:45 +0000

Guillain-Barr syndrome is a disorder in which the body’s immune system attacks part of the peripheral nervous system. The onset can be very rapid or take few days to few weeks. Symptoms are weakness or tingling sensations in the legs. Sometimes, the weakness and abnormal sensations spread to the arms and upper body and progress to paralysis. There is no known cure for Guillain-Barr syndrome, but therapies can lessen the severity of the illness and accelerate the recovery in most patients. Often life support is required until the patient begins to recover. As such, any treatment that can speed recovery is valuable. Currently, plasmapheresis and high-dose immunoglobulin therapy are most often used.

Both plasma exchange (PE) therapy and intravenous immune globulin (IVIG) have proven effective for Guillain-Barr syndrome (GBS). They are both thought todecrease autoantibody production and increase removal of immune complexes. Both have been shown to shorten recovery time by as much as 50%. IVIG is easier to administer and has fewer complications than PE. and is usually the initial treatment.

Randomized trials in severe disease show that IVIG started within 4 weeks from onset hastens recovery as much as plasma exchange. Combination therapy of both, does not improve outcomes or shortened illness duration over one or the other.

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Interferon for hypereosinophilic syndrome

M Levin, MD — Wed, 20 Jun 2012 22:29:04 +0000

Chronic myeloproliferative disorders (CMPD) are classified according to the WHO classification of 2001 as polycythemia vera (PV), chronic idiopathic myelofibrosis (CIMF), essential thrombocythemia (ET), CMPD/unclassifiable (CMPD-U), chronic neutrophilic leukemia, and chronic eosinophilic leukemia (CEL)/hypereosinophilic syndrome, all to be delineated as different from another member of the group, BCR/ABL-positive chronic myeloid leukemia (CML). This article addresses specifically the rare hypereosinophilic syndrome.

Hypereosinophilic syndromes (HES) and systemic mastocytosis (SMCD) are a group of disorders with clinical symptoms from local and remote effects of excessive proliferation of eosinophils, a type of a blood cell and mast cells, respectively. Interferon alpha (IFN-alpha), alone or in combination with other medications, can be a useful, and at times life-saving, treatment for patients with HES. Receptors for IFN-alpha are present on eosinophils, and clinical benefits are due to its effect on eosinophil growth, movement, activation, and survival. These effects are likely mediated through multiple pathways, not all of which are known or understood. A number of case reports showed that IFN-alpha has been life-saving for patients with intractable HES that were resistant to prednisone, hydroxyurea, and other agents used for myeloproliferative syndromes. There are reports of its combined use with hydroxyurea and prednisone. There are also reports of the use of peg-interferon.

Unfortunately, HES is rare and prospective trials are not reasonable to expect. I did find that the PDQ from the National Cancer Institute recommended interferon for this disease.

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