In the journal Clinical Case Reports, Bogojevic et al described a patient with seropositive rheumatoid arthritis and JAK2 V617F–positive polycythemia vera in whom the selective Janus kinase inhibitor tofacitinib demonstrated rheumatologic efficacy but minimal effect on polycythemia vera–related hematologic activity, highlighting the differential effects of Janus kinase inhibition across diseases driven by different Janus kinase isoforms.
The researchers noted that although Janus kinase (JAK) inhibitors are established in rheumatology, most selectively inhibit JAK1 and JAK3, sparing the activity of JAK2—a central driver in polycythemia vera (PV) pathogenesis. “These mechanistic insights underscore why tofacitinib, despite its broad immunomodulatory effects, would be expected to control autoimmune inflammation but exert limited impact on JAK2-driven disorders,” they wrote.
The authors stated that there are no prior published reports describing use of rheumatologic JAK inhibitors in patients with concomitant rheumatoid arthritis (RA) and PV.
Case Report
The report details the case of a 61-year-old woman who was diagnosed in February 2018 with seropositive RA based on chronic symmetric polyarthritis and positive autoantibodies. Laboratory testing at presentation revealed erythrocytosis, leukocytosis, and thrombocytosis, along with elevated inflammatory and immunologic markers, including rheumatoid factor and anti–cyclic citrullinated peptide antibodies. Hydroxychloroquine and corticosteroids were initiated; disease-modifying antirheumatic drugs were deferred pending hematologic evaluation.
In August 2018, bone marrow biopsy confirmed PV, with negative BCR-ABL testing. Between 2018 and 2021, the patient continuously received low-dose aspirin and cytoreductive therapy with hydroxyurea and underwent two therapeutic phlebotomies. Ultrasound imaging demonstrated splenomegaly (15 cm).
After nearly 3 years without rheumatology follow-up, methotrexate was initiated but later discontinued due to gastrointestinal intolerance. The patient was subsequently prescribed sulfasalazine, which was also withdrawn because of a diffuse skin rash. She was hospitalized for reassessment in April 2024, with a “high” 28-joint Disease Activity Score of 5.27, the researchers reported. As she was not found to meet the hematologic criteria for ruxolitinib initiation, treatment with 5 mg of tofacitinib twice daily was started in June; hydroxyurea was continued.
Treatment Response and Follow-Up
The researchers wrote that, within 3 months of initiating tofacitinib, the patient achieved both clinical and ultrasonographic remission of RA, with normalization of inflammatory markers and sustained relief from joint pain and stiffness.
Hematologic parameters were reported to remain stable throughout the follow-up period. According to the researchers, after 6 months, a “mild” improvement allowed reduction in hydroxyurea dosing; however, further tapering led to recurrence of erythrocytosis.
After 12 months, the patient remained in RA remission without experiencing adverse events or cytopenias.
“Tofacitinib effectively induced remission of RA in a patient with concomitant PV, demonstrating strong rheumatologic efficacy while maintaining hematologic safety,” the researchers concluded. “Its limited impact on erythrocytosis underscores the need for JAK2-directed therapies when treating patients with overlapping autoimmune and myeloproliferative diseases.”
Disclosure: The researchers reported no conflicts of interest and no external funding.
Source: Clinical Case Reports
