TY - JOUR
T1 - Treatment Strategies for GLILD in Common Variable Immunodeficiency: A Systematic Review
AU - Lamers, Olivia A. C.
AU - Smits, Bas M.
AU - Leavis, Helen Louisa
AU - de Bree, Godelieve J.
AU - Cunningham-Rundles, Charlotte
AU - Dalm, Virgil A. S. H.
AU - Ho, Hsi-En
AU - Hurst, John R.
AU - IJspeert, Hanna
AU - Prevaes, Sabine M. P. J.
AU - Robinson, Alex
AU - van Stigt, Astrid C.
AU - Terheggen-Lagro, Suzanne
AU - van de Ven, Annick A. J. M.
AU - Warnatz, Klaus
AU - van de Wijgert, Janneke H. H. M.
AU - van Montfrans, Joris
N1 - Funding Information: Financial support for this publication was provided by the Louise Vehmeijer Foundation, “e-GLILDnet” and the European Respiratory Society. Publisher Copyright: © Copyright © 2021 Lamers, Smits, Leavis, de Bree, Cunningham-Rundles, Dalm, Ho, Hurst, IJspeert, Prevaes, Robinson, van Stigt, Terheggen-Lagro, van de Ven, Warnatz, van de Wijgert and van Montfrans. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/4/15
Y1 - 2021/4/15
N2 - Introduction: Besides recurrent infections, a proportion of patients with Common Variable Immunodeficiency Disorders (CVID) may suffer from immune dysregulation such as granulomatous-lymphocytic interstitial lung disease (GLILD). The optimal treatment of this complication is currently unknown. Experienced-based expert opinions have been produced, but a systematic review of published treatment studies is lacking. Goals: To summarize and synthesize the published literature on the efficacy of treatments for GLILD in CVID. Methods: We performed a systematic review using the PRISMA guidelines. Papers describing treatment and outcomes in CVID patients with radiographic and/or histologic evidence of GLILD were included. Treatment regimens and outcomes of treatment were summarized. Results: 6124 papers were identified and 42, reporting information about 233 patients in total, were included for review. These papers described case series or small, uncontrolled studies of monotherapy with glucocorticoids or other immunosuppressants, rituximab monotherapy or rituximab plus azathioprine, abatacept, or hematopoietic stem cell transplantation (HSCT). Treatment response rates varied widely. Cross-study comparisons were complicated because different treatment regimens, follow-up periods, and outcome measures were used. There was a trend towards more frequent GLILD relapses in patients treated with corticosteroid monotherapy when compared to rituximab-containing treatment regimens based on qualitative endpoints. HSCT is a promising alternative to pharmacological treatment of GLILD, because it has the potential to not only contain symptoms, but also to resolve the underlying pathology. However, mortality, especially among immunocompromised patients, is high. Conclusions: We could not draw definitive conclusions regarding optimal pharmacological treatment for GLILD in CVID from the current literature since quantitative, well-controlled evidence was lacking. While HSCT might be considered a treatment option for GLILD in CVID, the risks related to the procedure are high. Our findings highlight the need for further research with uniform, objective and quantifiable endpoints. This should include international registries with standardized data collection including regular pulmonary function tests (with carbon monoxide-diffusion), uniform high-resolution chest CT radiographic scoring, and uniform treatment regimens, to facilitate comparison of treatment outcomes and ultimately randomized clinical trials.
AB - Introduction: Besides recurrent infections, a proportion of patients with Common Variable Immunodeficiency Disorders (CVID) may suffer from immune dysregulation such as granulomatous-lymphocytic interstitial lung disease (GLILD). The optimal treatment of this complication is currently unknown. Experienced-based expert opinions have been produced, but a systematic review of published treatment studies is lacking. Goals: To summarize and synthesize the published literature on the efficacy of treatments for GLILD in CVID. Methods: We performed a systematic review using the PRISMA guidelines. Papers describing treatment and outcomes in CVID patients with radiographic and/or histologic evidence of GLILD were included. Treatment regimens and outcomes of treatment were summarized. Results: 6124 papers were identified and 42, reporting information about 233 patients in total, were included for review. These papers described case series or small, uncontrolled studies of monotherapy with glucocorticoids or other immunosuppressants, rituximab monotherapy or rituximab plus azathioprine, abatacept, or hematopoietic stem cell transplantation (HSCT). Treatment response rates varied widely. Cross-study comparisons were complicated because different treatment regimens, follow-up periods, and outcome measures were used. There was a trend towards more frequent GLILD relapses in patients treated with corticosteroid monotherapy when compared to rituximab-containing treatment regimens based on qualitative endpoints. HSCT is a promising alternative to pharmacological treatment of GLILD, because it has the potential to not only contain symptoms, but also to resolve the underlying pathology. However, mortality, especially among immunocompromised patients, is high. Conclusions: We could not draw definitive conclusions regarding optimal pharmacological treatment for GLILD in CVID from the current literature since quantitative, well-controlled evidence was lacking. While HSCT might be considered a treatment option for GLILD in CVID, the risks related to the procedure are high. Our findings highlight the need for further research with uniform, objective and quantifiable endpoints. This should include international registries with standardized data collection including regular pulmonary function tests (with carbon monoxide-diffusion), uniform high-resolution chest CT radiographic scoring, and uniform treatment regimens, to facilitate comparison of treatment outcomes and ultimately randomized clinical trials.
KW - CVID
KW - GLILD
KW - common variable immunodeficiency
KW - granulomatous lymphocytic interstitial lung disease
KW - immunodeficiency
KW - systematic review
KW - treatment
UR - http://www.scopus.com/inward/record.url?scp=85105186607&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fimmu.2021.606099
DO - https://doi.org/10.3389/fimmu.2021.606099
M3 - Article
C2 - 33936030
SN - 1664-3224
VL - 12
JO - Frontiers in immunology
JF - Frontiers in immunology
M1 - 606099
ER -