Intravenous cyclophosphamide therapy for patients with severe ocular inflammatory diseases who failed other immunomodulatory therapies

Irmak Karaca; Elaine M Tran; SungWho Park; Albert Bromeo; Hassan Khojasteh; Anh Ngọc Tram Tran; Negin Yavari; Amir Akhavanrezayat; Cigdem Yasar; Gunay Uludag Kirimli; Ngoc Tuong Trong Than; Muhammad Hassan; Christopher Or; Hashem Ghoraba; Diana V Do; Quan Dong Nguyen

doi:10.1186/s12348-023-00372-z

Intravenous cyclophosphamide therapy for patients with severe ocular inflammatory diseases who failed other immunomodulatory therapies

J Ophthalmic Inflamm Infect. 2024 Mar 11;14(1):12. doi: 10.1186/s12348-023-00372-z.

Authors

Irmak Karaca¹, Elaine M Tran¹, SungWho Park¹, Albert Bromeo¹, Hassan Khojasteh¹, Anh Ngọc Tram Tran¹, Negin Yavari¹, Amir Akhavanrezayat¹, Cigdem Yasar¹, Gunay Uludag Kirimli¹, Ngoc Tuong Trong Than¹, Muhammad Hassan¹, Christopher Or¹, Hashem Ghoraba¹, Diana V Do¹, Quan Dong Nguyen²

Affiliations

¹ Spencer Center for Vision Research, Byers Eye Institute, Stanford University, Palo Alto, CA, USA.
² Spencer Center for Vision Research, Byers Eye Institute, Stanford University, Palo Alto, CA, USA. ndquan@stanford.edu.

Abstract

Background: Ocular inflammatory diseases, including scleritis and uveitis, have been widely treated with immunomodulatory therapies (IMTs) as a steroid-sparing approach. Such strategy includes conventional therapies (antimetabolites, alkylating agents, and calcineurin inhibitors) as well as biologic agents like adalimumab, infliximab, rituximab, and tocilizumab. Cyclophosphamide (CP) is an alkylating agent and mainly inhibits the functioning of both T and B cells. Though known to have potential adverse events, including bone marrow suppression, hemorrhagic cystitis, and sterility, CP has been shown to be efficacious, especially in recalcitrant cases and when used intravenous (IV) for a limited period.

Main findings: We conducted a retrospective case-series to assess the safety and efficacy of CP therapy for patients with severe ocular inflammatory diseases who failed other IMTs. Medical records of 1295 patients who presented to the Uveitis Clinic at the Byers Eye Institute at Stanford between 2017 and 2022 were reviewed. Seven patients (10 eyes) who received CP therapy for ocular inflammatory diseases with at least one year of follow-up were included. The mean age of the patients (4 males, 3 females) was 61.6 ± 14.9 (43.0-89.0) years. Clinical diagnoses included necrotizing scleritis (5 eyes), peripheral ulcerative keratitis (2 eyes), orbital pseudotumor (1 eye), HLA-B27 associated panuveitis and retinal vasculitis (2 eyes). Ocular disease was idiopathic in 3 patients, and was associated with rheumatoid arthritis, IgG-4 sclerosing disease, dermatomyositis, and ankylosing spondylitis in 1 patient each. All the patients had history of previous IMT use including methotrexate (5), mycophenolate mofetil (3), azathioprine (1), tacrolimus (1), adalimumab (2), infliximab (4), and rituximab (1). The mean follow-up time was 34.4 ± 11.0 (13-45) months, and mean duration of CP therapy was 11.9 ± 8.8 (5-28) months. Remission was achieved in 5 patients (71.4%). Four patients (57.1%) experienced transient leukopenia (white blood cell count < 4000/mL).

Short conclusion: CP therapy can be considered a potentially effective and relatively safe therapeutic option for patients with severe ocular inflammatory diseases who failed other IMTs including biologics (TNFa and CD20 inhibitors).

Keywords: Cyclophosphamide; Immunomodulatory therapy; Refractory; Scleritis; Severe; Uveitis.