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Is there a role for steroids in interstitial lung disease in CVID?

Published: December 29, 2022

Common variable immunodeficiency (CVID) is the most prevalent immunodeficiency, characterized by the reduction of IgG and IgA and disturbed specific antibody responses. While nearly all patients suffer from respiratory tract infections up to half of the patients have additional symptoms related to an autoreactive immune system. In about 20% of CVID patients, this autoimmunity targets the lungs, where it causes an inflammatory interstitial lung disease typically termed granulomatous lymphocytic interstitial lung disease (GLILD). Currently, there is no standardized treatment for patients with CVID and GLILD. Because of the potentially poor prognosis of GLILD and its autoimmune character, different immunosuppressive regimes including corticosteroids, rituximab, azathioprine, mycophenolate, or combinations thereof and others have been used to control this disease manifestation. Although corticosteroids have been suggested as first line therapy for GLILD in a British consensus paper, there are no studies that show whether corticosteroids should have a place in the treatment of GLILD and how safe their use in immunodeficient patients is.

The study by Smits et al. published in The Journal of Allergy and Clinical Immunology (JACI) investigated the safety and effectivity of corticosteroids as a first line treatment for interstitial lung disease in CVID. The study investigated 79 CVID patients with GLILD from the STILPAD study, a large observational multicenter trial. 56 patients in the corticosteroid group had received high-dose corticosteroids (≥0.3 mg/kg and ≥30mg prednisone equivalent dose) and 23 patients in the control group had not received any immunosuppressants during the observation period. This study collected baseline and follow-up chest CT scans, pulmonary function tests (PFT), biomarkers, quality of life questionnaire data, infection rates and corticosteroid related side effects.

Treatment effectivity was assessed using GLILD chest CT scores and PFT results. Follow-up examinations over 0.3 to 16.7 years served to determine the duration of remission. Safety of corticosteroid treatment of GLILD in CVID was assessed by comparing infection rates and occurrence of side effects potentially related to corticosteroids between the corticosteroid group and the control group.

Both the chest CT scores and PFT parameters improved in the corticosteroid group, while only one PFT parameter improved in the control group. Follow-up data showed prolonged remission in 42% of corticosteroid-treated patients. This treatment significantly reduced the levels of GLILD associated biomarkers and improved reported dyspnea. When relapse occurred retreatment with corticosteroids was however effective in only 20% of patients.
While overall infection rates did not differ between the corticosteroid and the control group, the only two opportunistic infections occurred in two patients during maintenance therapy with corticosteroids. Additionally, osteoporosis and osteoporotic fractures were more frequent among patients treated with corticosteroids, especially under maintenance therapy.

Short-term high-dose corticosteroids appear to be an effective, safe, affordable, and widely available first-line treatment option for GLILD. However, prolonged corticosteroid treatment seems to have no additional effect and increases the risk of side effects. Retreatment with corticosteroids after relapse is rarely effective. Therefore, patients failing corticosteroid treatment or having side effects require alternative immunosuppressive treatment options without delay. Future research needs to investigate predictive parameters for patients prone to fail corticosteroid treatment, so that alternative treatment strategies like the previously reported combination of rituximab and azathioprine or mycophenolate mofetil can be initiated immediately.

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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