Iron Deficiency Is Commonly Observed in Female Multiple Sclerosis (MS) Patients with Relapsed/Refractory or Primary Progressive Disease Referred for Biological Therapies

Introduction

Iron deficiency with or without anemia is common, symptomatic, and often underdiagnosed in women. Aging related iron deposition in the brain has been associated with multiple chronic neurological conditions, including multiple sclerosis (MS). MS is an autoimmune and inflammatory neurologic disease with a variable presentation and disease severity resulting from demyelination in the central nervous system. In MS, iron deficiency has been associated with more severe depressive symptoms and poorer quality of life. Overlapping symptoms shared by iron deficient and MS patients include fatigue, cognitive dysfunction and restless leg. Recognizing and treating iron deficiency is important in MS patients and may play a role in improving quality of life.

Methods

We conducted a retrospective study from January 2017 to December 2021 of MS patients referred to OHSU hematology clinic for therapy with monoclonal antibodies including ocrelizumab, rituximab, or natalizumab. Patient demographic, clinical, treatment and laboratory characteristics were reviewed. Iron deficiency was defined by presence of Ferritin < 50 ng/ml. Patients identified as iron deficient were reviewed for further gastro-intestinal and gynecologic work-up.

Results

A total of 307 patients with MS were identified. The median age was 49.3 (range 18-84), 104 were males (average age 50.7 at time of study) and 203 were female (average age 48.5 years at time of study). The majority of patients received ocrelizumab, with a minority receiving rituximab due to insurance coverage and rare patients receiving natalizumab. Ferritin levels were available in 114 patients. Of 20 male patients whose ferritin was checked, 4 were iron deficient. Of 94 female patients whose ferritin was checked, 56 (60%) were found to have past or current iron deficiency. In 15 of these 56 patients, GI findings were noted including: rectal cancer, adenomas, esophagitis, gastritis, large hiatal hernias, inflammatory bowel disease, H. pylori and bariatric surgery. The average age of women with GI findings was 48.7 years with an average ferritin of 19.2 ng/ml. In 12 patients, obstetric and gynecologic conditions were diagnosed. The average age of women with OB/GYN sources was 31.2 years with an average ferritin of 21 ng/ml (range). Three patients had combined GI and GYN causes, 4 were pending GI evaluations and 22 were not worked up for cause. Twenty-two women received treatment with intravenous iron products (iron dextran, iron sucrose, ferumoxytol, ferric carboxymaltose). In the 22 women treated with intravenous iron, 4 developed progressive MS symptoms leading to change in therapy.

Conclusion

Results show a high frequency of iron deficiency in women with multiple sclerosis. GI and GYN sources were the main causes for iron deficiency. Intravenous iron was used in a subset of patients with iron deficiency. Worsening MS related symptoms were observed in 4 patients treated with intravenous iron. All women with multiple sclerosis should be evaluated for iron deficiency and investigated for cause if iron deficiency is found. Future studies on the effects of adequately diagnosing and treating iron deficiency in patients with multiple sclerosis are warranted.

No relevant conflicts of interest to declare.