Baricitinib in Pediatric ITP: A Novel Case-Based Insight and Literature Overview

Abstract

Immune thrombocytopenia is an autoimmune disease, which is defined by abnormal amounts of platelets due to increased breakdown and dysfunction of platelet production. First-line treatments such as corticosteroids and intravenous immunoglobulins are considered the gold standard, but some patients, including children, present with refractory disease where second-line treatments are required. Baricitinib - a Janus kinase (JAK) 1/2 inhibitor and a potential new treatment option for ITP in general. This is a case report of a 16-year-old female with refractory ITP and alopecia areata treated with baricitinib which successfully offered the drug's efficacy and safety within the pediatric population.

Introduction

Immune thrombocytopenia is an autoimmune condition that results in rapid destruction and decreased production of platelets, resulting in thrombocytopenia and risk of bleeding. First-line standard treatments are corticosteroids, as well as intravenous immunoglobulins, but for patients who do not respond to these, as well as for those whose disease persists, a significant percentage of whom up to 47% are pediatric, second-line therapies are required. Baricitinib, an oral Janus kinase (JAK) 1/2 inhibitor, has demonstrated efficacy in various autoimmune diseases and has been associated with increased platelet counts in treated patients. This case study explores the use of baricitinib in a pediatric patient with refractory ITP and concurrent alopecia areata.

Case Presentation

A 16-year-old female was admitted to the emergency department with a two-month history of progressive asthenia, which worsened over the last two weeks. She also complained of menorrhagia and significant hair loss. She had a history of atopic dermatitis and a family history of acute myeloid leukemia in a first-degree relative.

On physical examination, the patient was pale with petechiae on the lower extremities and a 3 cm alopecic patch on the scalp. Laboratory investigations showed severe microcytic anemia, a hemoglobin of 6.5 g/dL, an elevated reticulocyte count of 5.2%, and profound thrombocytopenia, with a platelet count of 6 × 10⁹ /L. Microcytic, hypochromic erythrocytes were noted in the peripheral smear, with no platelet clumping. Ferritin level was low (8.6 ng/mL) with a trend for iron deficiency anemia. The liver enzyme was mildly elevated. The patient was admitted to further evaluate and manage the situation.

Diagnostic Workup

Severe thrombocytopenia and anemia were noted. An extensive investigation was carried out to find any potential causes. Bone marrow aspiration and biopsy were done and revealed normal cellularity with increased megakaryocytes, suggesting peripheral platelet destruction. Autoimmune screening revealed positive antiplatelet antibodies, hence ITP diagnosis. Another finding was a scalp alopecic patch that suggested the diagnosis of alopecia areata, which is an autoimmune disease often found with other autoimmune diseases such as ITP.

Treatment Course

The patient was initially managed with high-dose intravenous corticosteroids (methylprednisolone 1 g/day for three days) and intravenous immunoglobulins (1 g/kg). Despite this, her platelet count remained below 10 × 10⁹/L, and she continued to experience menorrhagia and mucocutaneous bleeding. Given the refractory nature of her ITP and the concurrent alopecia areata, a decision was made to initiate baricitinib therapy.

Baricitinib was initiated at a dose of 4 mg/day with regular checks on blood counts and other adverse effects. After two weeks, her platelet count reached 50 × 10⁹/L, and the bleeding symptoms improved. Over the following month, her platelet count has stabilized over 100 × 10⁹/L and had normalized levels of hemoglobin with iron supplementation. Partial regrowth was also seen in scalp hair.

Discussion

This case demonstrates the possible effectiveness of baricitinib in a pediatric patient with refractory ITP. Baricitinib is a selective inhibitor of JAK1 and JAK2, key mediators of multiple cytokines involved in the signaling pathways involved in immune regulation. Through the modulation of these pathways, baricitinib may reduce the autoimmune-mediated destruction of platelets and improve platelet production.

Recent studies have investigated the use of baricitinib in adult patients with ITP. A phase 2 trial tested baricitinib in combination with high-dose dexamethasone as a first-line treatment for newly diagnosed ITP, with promising results regarding durable response rates. Another open-label pilot study evaluated baricitinib in steroid-resistant or relapsed ITP, showing favorable outcomes with manageable safety profiles.

The mechanism by which baricitinib increases platelet counts is not fully elucidated but is thought to involve modulation of cytokine signaling that reduces platelet destruction and may enhance thrombopoietin signaling, thereby promoting platelet production. Additionally, baricitinib's immunomodulatory effects may ameliorate other autoimmune manifestations, as observed in this patient with concurrent alopecia areata.

Conclusion

Baricitinib could be a promising therapeutic agent in children with refractory ITP, especially when combined with other autoimmune diseases. This case points out the necessity of further studies to determine the safety and efficacy of baricitinib in pediatric patients. The clinicians must weigh the potential benefits of using baricitinib in such cases while monitoring closely for adverse effects.

References

1. Zhao P, An Z, Fu H, et al. "Baricitinib in Combination with High-Dose Dexamethasone As First-Line Treatment for Newly Diagnosed Immune Thrombocytopenia: A Prospective, Multicenter, Randomized Trial." Blood, 2023; 142(Supplement 1):1207.

2. Shen X, Li R, Wang Y, et al. "Efficacy and Safety of Baricitinib in Steroid-Resistant or Relapsed Immune Thrombocytopenia: A Pilot Study." Journal of Autoimmunity, 2023;138:102998

3. López de Hontanar Torres G, Zubicaray J, Sebastián E, Hernández-Martín A, Iriondo J and Sevilla J (2024) Baricitinib in pediatric chronic immune thrombocytopenia and associated autoimmune conditions: a case report. Front. Pediatr. 12:1516039.

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