2 Minute Medicine Rewind March 13, 2017

Post-babesiosis warm autoimmune hemolytic anemia

Incidence of babesiosis has increased in the last decade, especially in the New England region of the United States. While non-immune mediated hemolysis occurs during an active babesiosis infection with resolution once a patient begins antibiotics and clears the parasite, warm autoimmune hemolytic anemia (WAHA) has been seen in patients after treatment and recovery. In order to explore the frequency of these cases, authors conducted a retrospective cohort study looking at medical records of all babesiosis patients who were cared for at their center from January 2009 to June 2016 (n = 86). 18 of these patients were asplenic. They found 6 patients who met the standard criteria confirming presence of a warm autoantibody, all of which developed WAHA between 2 and 4 weeks after their babesiosis diagnosis and had already surmounted substantial responses to antimicrobial treatment, including parasite clearance. All 6 patients shared a history of splenectomy, tested positive for direct antiglobulin tests for immunoglobulin G and complement component 3, and did not have a history of autoimmune disease. Four patients required immunosuppressive treatment for WAHA in the form of glucocorticoids or prednisone combined with cyclophosphamide; two patients’ WAHA resolved on their own. In conclusion, authors recommend screening for WAHA in babesiosis patients with worsening hemolytic anemia after treatment, especially if they are asplenic.

Cytokine inhibition in patients with chronic fatigue syndrome

One hypothesis for the cause of chronic fatigue syndrome, often termed myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), is the overproduction of proinflammatory cytokines like interleukin-1 (IL-1). Researchers conducted this randomized, double-blind, placebo-controlled trial from July 2014 to May 2016 in order to evaluate the effect of giving CFS patients subcutaneous anakinra, a powerful IL-1 antagonist often utilized for rheumatoid arthritis. 50 women aged 18 to 59 who met the CDC’s CFS criteria were included, which requires 6 months or more of severe disabling fatigue with at least four other symptoms from the following: postexertional malaise, unrefreshing sleep, memory impairment, headache, muscle pain, tender lymph nodes, sore throat, or joint pain. Patients were randomly assigned to either 100 mg subcutaneous anakinra or placebo daily for 4 weeks and were then followed for an additional 20 weeks. Researchers found no significant difference in the primary end point of fatigue severity score at 4 weeks, measured by the Checklist Individual Strength subscale (mean difference 1.5 points, 95% CI: -4.1 to 7.2). No difference was observed at the end of the 20 week follow-up period. 2 of 25 anakinra patients and 5 of 25 placebo patients achieved fatigue alleviation to a level within the healthy range. Researchers conclude that IL-1 inhibition using anakinra does not result in significant relief in fatigue severity in women with CFS, but they do cite the study’s small sample size and short study duration as limitations.

Long-term outcomes of imatinib treatment for chronic myeloid leukemia

The 2003 IRIS trial established imatinib, a selective BCR-ABL kinase inhibitor, as the standard treatment for chronic myeloid leukemia. This was an open-label, multicenter, randomized control trial across 16 countries that assigned 1106 patients with newly diagnosed CML at the time to imatinib or interferon alfa and cytarabine. The initial study reported results at 18 months, with a follow up study published 5 years later demonstrating continued durable responses to imatinib. This current analysis aimed to continue investigating the long term effects of imatinib in this group after more than 10 years of follow-up. The primary long-term outcome was overall survival. Secondary outcomes included response rates, disease progression, safety, and drug-related adverse events. After a median period of 10.9 years, CML patients on imatinib had an 83.3% overall survival rate (95% CI: 80.1 to 86.6). There was an 89.0% cumulative rate of major cytogenetic response and 82.8% rate of complete cytogenetic response. Only 51 of 551 randomly assigned imatinib patients experienced serious drug related adverse events, most occurring within the first year of treatment and consisting of abdominal pain. Researchers found no cumulative or late toxicity and no new safety signals. Therefore, this new information continues to demonstrate the robust, long term efficacy and safety of imatinib as the first line treatment for CML.

Risk of serious infections associated with use of immunosuppressive agents in pregnant women with autoimmune inflammatory conditions

Autoimmune inflammatory conditions affect approximately 3-4 million Americans, many of which are female and in their childbearing years. Studies of the risk of infections associated with taking immunosuppressive therapy have been abundant in the general population but lacking in pregnant women. This was an observational cohort study involving 4961 pregnant women to compare the risk of serious infections associated with the use of systemic steroids, non-biologic agents, or tumor necrosis factor α (TNF) inhibitors. Information was gathered from two large health insurance databases, Medicaid (2001-2010) and Optum Clinformatics (2004-2015). Women had a diagnosis of systemic lupus erythematosus, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, or inflammatory bowel disease. 71 (0.2% of 4961) pregnant women experienced the primary outcome of serious infection during pregnancy, defined by hospital admission for bacterial or opportunistic infection. There were no significant differences found in risk between the three drug categories: non-biologic agents vs. steroids, HR 0.81 (95% CI: 0.48 to 1.37); TNF inhibitors vs. steroids, 0.91 (0.36 to 2.26); TNF inhibitors vs. non-biologic agents, 1.36 (0.47 to 3.93). A higher daily dose of steroids was associated with increased risk (coefficient for each unit increase in average prednisone equivalent mg daily dose = 0.019, p = 0.02). Researchers conclude that while the risk of infection among pregnant women with autoimmune inflammatory conditions is similar among drug classes, women receiving high dose steroids during pregnancy should be monitored closely for development of serious infection.

Doxycycline versus prednisolone as an initial treatment for bullous pemphigoid

Bullous cutaneous pemphigoid is an autoimmune blistering skin disorder in which autoantibodies attack the dermal-epidermal junction. The standard of treatment for over 50 years has been oral prednisolone, and studies to find a suitable oral alternative have been lacking. In this multicenter, parallel-group, randomized control trial, 132 patients with bullous pemphigoid were randomly assigned to 200 mg of doxycycline or 0.5 mg/kg of prednisolone daily to assess whether doxycycline would produce acceptable short-term blister control while having long-term safety advantages over standard treatment. As hypothesized, the primary effectiveness outcome was greater for prednisolone: 91% of prednisolone patients versus 74% of doxycycline patients had three or fewer blisters at 6 weeks (adjusted difference of 18.6%, 90% CI: 11.1 to 26.1). However, this upper bound CI fell within the 37% pre-specified acceptable non-inferiority margin. The primary safety outcome was significantly greater for doxycycline: 18% of doxycycline patients versus 36% of prednisolone patients had severe, life-threatening, and fatal events by 52 weeks (adjusted difference of 19.0%, 95% CI: 7.0 to 30.1, p = 0.001). This study shows that even though prednisolone may yield slightly more efficacious results, oral doxycycline treatment for bullous pemphigoid is a non-inferior option that produces adequate symptom control and is safer in the long term.

Image: PD

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