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Voice Over: Hi there. I’m Dr. Rahul Dixit, a practicing gastroenterologist based out of Santa Monica, California.

At my single-specialty practice, I see a lot of young, adult patients with a wide variety of pathology. During my experience, I’ve come across many patients who have developed iron deficiency anemia as a result of their gastrointestinal or GI conditions. Let’s begin our discussion today with the identification and diagnosis of iron deficiency anemia.

Identification and diagnosis

What is iron deficiency anemia, or IDA?

IDA occurs when the balance of iron intake, existing iron stores, and iron depletion cannot fully support the production of erythrocytes.

There are 3 main causes of IDA: blood loss, insufficient absorption of iron, and insufficient intake of iron. Some examples of these causes include: peptic ulcers, colon cancer, Crohn’s disease, celiac disease, and decreased absorption after intestinal surgeries, such as bariatric surgery.

Because anemia can often be found in patients with a variety of GI conditions, your patients may be at high risk of developing IDA.

For instance, IDA is particularly prevalent in patients with celiac disease, gastrointestinal bleeding, inflammatory bowel disease, or IBD, and patients who have had bariatric surgery.

For instance, bariatric gastric bypass surgery disrupts the physiological absorption of iron in the duodenum by decreasing the area available to absorb iron.

There are 2 types of iron deficiency: absolute and functional.

Absolute iron deficiency occurs when the body’s iron stores are depleted due to low dietary iron intake, impaired iron absorption, or excessive iron loss. Functional iron deficiency occurs when there are adequate iron stores, but insufficient mobilization of iron in the body.

Hepcidin is a protein that serves as a regulator of the entry of iron into the circulatory system. In functional iron deficiency, iron release and absorption are blocked by high hepcidin levels. In patients with IDA, hepcidin suppression may also be an early sign of absolute iron deficiency along with decreased TSAT and ferritin.

IDA may be difficult to spot in your practice because the symptoms aren’t ones patients normally report to a gastroenterologist. Some patients with mild to moderate IDA may exhibit non-specific symptoms, or may even be completely asymptomatic.

In more severe cases, you may see patients who experience signs and symptoms that include: weakness, fatigue, pica, shortness of breath, arrhythmia, pale skin, sore tongue, tinnitus, brittle nails, hair loss, headache, chest pain, coldness in the hands and feet, and dizziness.

IDA is frequently underreported, so to prevent misdiagnosis, I tend to ask my patients about specific symptoms that can be caused by IDA. If your patients have any of the previously mentioned conditions that contribute to IDA risk, it is important to routinely test their iron levels, even when your patients aren’t exhibiting symptoms.

There are 3 key indices for evaluating IDA: hemoglobin, transferrin saturation or TSAT, and ferritin.

I believe that IDA screening is an important part of care for my patients. However, current screening and management practices may be suboptimal.

A study of 836 adult patients who were newly diagnosed with ulcerative colitis was conducted to assess frequency of iron deficiency screening and treatment in patients who developed anemia. This analysis showed that of the 585 adult patients who developed anemia, nearly 1/3 went unscreened for an iron study evaluation.

This study also showed that of those patients who were diagnosed, nearly 25% did not receive oral iron supplementation. Furthermore, none of the patients treated for IDA received IV iron.

Let’s examine a hypothetical case for a patient with IDA.

Meet Sara. Sara is 26 years old and has been struggling with ulcerative colitis. She is currently being treated with a corticosteroid and she was shown to be intolerant to oral iron in the past. In addition to having 4-5 episodes of bloody diarrhea per day, Sara also reported generalized malaise and mild dyspnea on exertion. Lab testing shows that her hemoglobin level is 10.5 grams per deciliter, which falls below the lower threshold of normal. Let’s explore potential treatment options for patients like Sara who you may see in your practice.

Treatment goals and options

The optimal outcome of treatment for IDA is iron repletion above the lower threshold of normal. This means that the patient’s TSAT, ferritin, and hemoglobin must be within normal ranges.

There are two treatment options for patients diagnosed with IDA: oral iron and intravenous or IV iron. Both forms of treatment have pros and cons to consider for your patients’ individual needs.

I usually start with oral iron for all of my patients with IDA as first-line therapy. It is obtainable without a prescription, can be readily found at a pharmacy, and has a dosage of 1 to 3 times a day. However, oral iron absorption can be inhibited due to a variety of conditions, which can interfere with digestive processes and compromise its efficacy.

Even in healthy patients, less than 10% of oral iron is absorbed due to the fact that the duodenum can maximally absorb only 10 to 20 mg daily. That means nearly 90% of oral iron may be going to waste. Additionally, reports indicate that adherence rates range from 40%-60% for oral iron therapy. This may be due to the side effects of oral iron, which include epigastric discomfort, nausea, vomiting, diarrhea, and constipation.

If patients in my practice are 4-8 weeks into treatment and their iron levels are still not within normal limits, oral iron may be the wrong option for them.

IV iron may be an option for your patients if oral iron fails. 100% of IV iron is delivered into the bloodstream, so your patients can restore their iron in less time.

As IV iron may only be administered in an infusion center by a healthcare professional, it may be less convenient for some patients. Although every infusion experience is different, some of your patients may be more familiar with infusions due to other conditions for which they already receive similar treatment. Whether you infuse in your office or not, it is important to monitor your patients’ labs throughout their treatment journey to see if their therapy is working.

Some side effects for IV iron include nausea, hypertension, injection site reactions, hypotension, and headache. Serious hypersensitivity reactions may also occur. If you are unfamiliar with IV iron treatment options, it is important to note that dextran-free IV iron options are now available.

Let’s revisit Sara, the hypothetical patient with ulcerative colitis who showed low hemoglobin levels.

In order to assess whether Sara has developed IDA, Sara’s doctor ordered tests for her ferritin and TSAT levels. These results showed that Sara is low across all three indices, confirming that she does, in fact, have IDA. Given what we already know about Sara’s previously reported intolerance to oral iron, how would you proceed with her care? Next, we will explore an IV iron treatment option that may be appropriate for a patient like Sara.

Treating with Injectafer

Injectafer is an iron replacement product indicated for the treatment of IDA in patients who have intolerance or have had unsatisfactory response to oral iron, or adult patients who have non-dialysis dependent chronic kidney disease. Injectafer is a dextran-free IV iron.

Injectafer can be used after oral iron failure in patients with IDA of various etiologies. Some of these etiologies may contribute to iron deficits of approximately 1500 mg. These include cancer, a wide range of GI pathologies, abnormal uterine bleeding, post-partum bleeding, post-gastric bypass, and heart failure, as well as non–dialysis dependent chronic kidney disease.

Injectafer has a carbohydrate shell that is tightly bound around a colloidal iron (III) hydroxide core. This molecular structure was designed for the controlled release of iron to deliver 1500 mg in 2 administrations of 750 mg separated by at least 7 days.

Let’s examine the efficacy and safety data for Injectafer in adult patients with IDA when compared to oral iron and iron sucrose.

This study was designed as a randomized, open-label, active-controlled, multicenter trial with 1011 adult subjects randomized at 84 US centers.

Inclusion criteria for the study were that patients had to have hemoglobin levels of ≤11.0 g/dL, ferritin levels ≤100 ng/mL, or ≤300 ng/mL when TSAT ≤30%, and IDA of any etiology, including heavy uterine bleeding; GI disorders; postpartum, nutritional, or dietary deficiency; and others. Patients with a history of iron intolerance and a history of drug allergy were also included.

After a 14-day run-in period of oral ferrous sulfate dosed at 325 mg, 3 times daily, eligible patients with hemoglobin <12 g/dL who had an inadequate response to oral iron were randomized to receive ferric carboxymaltose or to continue oral iron therapy. These patients formed Cohort 1. Those who were unable to tolerate or were inappropriate for oral iron (subjects inappropriate for oral iron were not included in the indication for Injectafer) during the run-in period were randomized to receive ferric carboxymaltose or standard-of-care IV iron treatment, thus forming Cohort 2.

The primary endpoint of the study was mean change to highest observed hemoglobin from baseline to day 35 or time of intervention for subjects in Cohort 1. The same measurement was a secondary endpoint in Cohort 2.

In Cohort 1, results showed that Injectafer provided significantly greater increases in hemoglobin levels vs oral iron to day 35, and improvements in hemoglobin were greater with Injectafer vs oral iron (1.6 vs 0.8 respectively). Also, the mean change in iron indices was greater with Injectafer vs oral iron from baseline to day 35 or time of intervention.

One other point of note is that by the end of the study, patients supplemented with oral iron demonstrated diminished iron stores, as seen by the ferritin and TSAT levels, compared to their baseline levels, suggesting that iron losses outpaced oral iron supplementation.

In Cohort 2, the mean change in hemoglobin from baseline to highest value between baseline and day 35 or time of intervention was greater with Injectafer vs iron sucrose. Furthermore, the mean change in ferritin and TSAT was greater with Injectafer vs iron sucrose during that time period.

The composite safety endpoint for Cohorts 1 and 2 included all-cause mortality, nonfatal myocardial infarction, nonfatal stroke, unstable angina requiring hospitalization, congestive heart failure, arrhythmias, and protocol-defined hypotension or hypertension.

Seven participants (2.9%) in Group A (Injectafer), 4 (1.6%) in Group B (oral iron), 10 (4%) in Group C (Injectafer), and 12 (4.9%) in Group D (iron sucrose) met the primary composite safety endpoint.

The most commonly observed components of the composite safety endpoint were protocol-defined hypertension and death due to any cause. Injectafer has real-world experience that supports its use for patients with IDA.

Let’s wrap up our conversation with Sara, the hypothetical patient we have previously spoken about. Sara’s labs showed that her hemoglobin, ferritin, and TSAT levels were all below normal. Because Sara is also oral-iron intolerant, she was prescribed Injectafer.

Approximately 4 weeks after her infusion, her doctor ordered another round of labs which showed that Sara’s hemoglobin had risen from 10.5 grams per deciliter to a normal level of 12.1 grams per deciliter. Her TSAT and ferritin levels had also risen (21% and 20 ng/mL, respectively).

If you see patients like Sara in your practice, you might want to consider Injectafer.

To learn more about Injectafer, including the Full Prescribing Information, patient savings offerings, and more, visit injectaferhcp.com.