Abstract
Objective: To determine the prevalence of persistent hypogammaglobulinemia in patients with autoimmune rheumatic diseases receiving rituximab.
Methods: A retrospective, cross-sectional, single-center study conducted on patients with autoimmune rheumatic diseases who attended the outpatient Rheumatology Clinic at the Dr. Antonio Fraga Mouret Specialty Hospital, Centro Médico Nacional La Raza, Mexico City, between January 2013 and January 2018, for rituximab treatment. Data analysis was performed using descriptive and inferential statistics to evaluate serum immunoglobulin levels, clinical and demographic characteristics, diagnosis, and treatment.
Results: A total of 262 patients with autoimmune rheumatic diseases who received rituximab were included. Eight cases (six women and two men) of persistent hypogammaglobulinemia were identified, representing a prevalence of 3.1% of the total population. No factors associated with hypogammaglobulinemia were identified.
Conclusions: To date, no prognostic or predictive factors have been associated with persistent hypogammaglobulinemia. Additional prospective studies are required to better understand the implications of persistent hypogammaglobulinemia in patients with autoimmune diseases.
References
Otani I. Lehman H, Jongco A. Practical guidance for the diagnosis and management of secondary hypogammaglobinemia: A Work Group Report of the AAAAI Primary Immunodeficiency and Altered Immune Response Committees. J Allergy Clin Immunol 2022; 149: 1525-60. doi: 10.1016/j.jaci.2022.01.025
Velásquez-Ortiz MG, O’Farril-Romanillos PM, Berrón-Ruiz L. Conceptos generales de las inmunodeficiencias humorales. Rev Alerg Mex 2020; 67 (2): 142-164. doi: 10.29262/ram.v67i2.763
Tangye SG, Al-Herz W, Bousfiha A, et al. The ever-increasing array of novel inborn errors of immunity: an interim update by the IUIS committee. J Clin Immunol 2021; 41 (3):666-679. doi: 10.1007/s10875-021-00980-1
Leandro MJ. Infections related to biologics: agents targeting B cells. Infect Dis Clin North Am 2020; 34: 161-178. doi: 10.1016/j.idc.2020.02.013
Pavlasova G, Mraz M. The regulation and function of CD20: an ‘enigma’ of B-cell biology and targeted therapy. Haematologica 2020; 105: 1494-1506. doi: 10.3324/haematol.2019.243543
Kridin K, Ahmed AR. Post-rituximab immunoglobulin M (IgM) hypogammaglobulinemia. Autoimmun Rev 2020; 19: 102466. doi: 10.1016/j.autrev.2020.10246
Tuano SK, Seth N, Chinen J. Secondary immunodeficiencies: An overwiew. Annals Allergy Asthma Immunol 2021; 127 (6): 617-626. doi: 10.1016/j.anai.2021.08.413
Ohigashi H. Sustained CD4 and CD8 lymphopenia after rituximab maintenance therapy following bendamustine and rituximab combination therapy for lymphoma. Leuk Lymphoma 2015; 56 (11): 3216-8. doi: 10.3109/10428194.2015.1026818
Delate T, Hansen ML, Gutierrez AC, et al. Indications for rituximab use in an integrated health care delivery system. J Manag Care Spec Pharm 2020; 26: 832-838. doi: 10.18553/jmcp.2020.26.7.832
Kaplan B, Bonagura V. Secondary Hypogammaglobulinemia An Increasingly Recognized Complication of Treatment with Immunomodulators and After Solid Organ Trasplantation. Immunol Allerfy Clin N Am 2019; 39: 31-47. doi: 10.1016/j.iac.2018.08.005
Van Vollenhoven RF, Emery P, Bingham III CO, Keystone EC, et al. Long-term safety of Rituximab in rheumatoid arthritis: 9.5-year follow-up of the global clinical trial programme with a focus on adverse events of interest in RA patients. Ann Rheum Dis 2013; 72: 1496-1502 doi: 10.1136/annrheumdis-2012-201956
Luterbacher F, Bernard F, Baleydier F, Ranza E, et al. Case Report: Persistent hypogammaglobulinemia More Than 10 Years After Rituximab Given Post-HSCT. Front Immunol 2021; 12: 773853. doi: 10.3389/fimmu.2021.773853
Christou EAA, Giardino G, Worth A, Ladomenou F. Risk factors predisposing to the development of hypogammaglobulinemia and infections post-Rituximab. Int Rev Immunol 2017; 36: 1-8. Doi: 10.1080/08830185.2017.1346092
Khojah AM, Miller ML, Klein-Gitelman MS, et al. Rituximab-associated Hypogammaglobulinemia in pediatric patients with autoimmune diseases. Pediatr Rheumatol Online J 2019; 17 (1): 61. doi: 10.1186/s12969-019-0365-y
Fernández-Romero DS, Torre MG, Larrauri BJ, Malbran E, et al. Rituximab e hipogammaglobulinemia. Medicina (Buenos Aires); Medicina (Buenos Aires); 75; 5; 10-2015; 319-323.
Besada E, Koldingsnes W, Nossent JC. Serum immunoglobulin levels and risk factors for hypogammaglobulinaemia during long-term maintenance therapy with Rituximab in patients with granulomatosis with polyangiitis. Rheumatol 2014; 53 (10): 1818-24. doi: 10.1093/rheumatology/keu194
Boleto G, Avouac J, Wipff J, et al. Predictors of hypogammaglobulinemiaduring rituximab maintenance therapy in rheumatoid arthritis: a 12-year longitudinal multi-center study. Semin Arthritis Rheum 2018; 48 (2): 149-154. doi: 10.1016/j.semarthrit.2018.02.010
Marco H, Smith RM, Jones RB, Guerry MJ, et al. The effect of Rituximab therapy on immunoglobulin levels in patients with multisystem autoimmune disease. BMC Musculoskelet Disord 2014; 25 (15): 178. doi: 10.1186/1471-2474-15-178
Casulo C, Maragulia J, Zelenetz AD. Incidence of hypogammaglobulinemia in patients receiving Rituximab and the use of intravenous immunoglobulin for recurrent infections. Clin Lymphoma Myeloma Leuk 2013; 13 (2): 106-111. doi: 10.1016/j.clml.2012.11.011
Cortazar FB, Pendergraft WF, Wenger J, Owens CT, et al. Effect of Continuous B Cell Depletion With Rituximab on Pathogenic Autoantibodies and Total IgG Levels in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis. Arthritis Rheumatol 2017; 69 (5): 1045-1053. doi: 10.1002/art.40032
Olfat M, Silverman ED, Levy DM. Rituximab therapy has a rapid and durable response for refractory cytopenia in childhood-onset systemic lupus erythematosus. Lupus 2015; 24 (9): 966-72. doi: 10.1177/0961203315578764
Kaplan B, Kopyltsova Y, Khokhar A, Lam F, et al. Rituximab and immune deficiency: case series and review of the literature. J. Allergy Clin. Immunol 2014; 2 (5): 594-600. doi: 10.1016/j.jaip.2014.06.003
Sacco KA, Abraham RS. Consequences of B-cell-depleting therapy: hypogammaglobulinemia and impaired B-cell reconstitution. Immunother 2018; 10 (8): 713-728. doi: 10.2217/imt-2017-0178
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