Cohort study of off-label use of low-dose IL-2 therapy for systemic autoimmune diseases

Tabaa, Omar Al; Hamroun, S.; Leplay, Céline; Fain, Olivier; Klatzmann, David; Mékinian, A.

doi:10.55563/clinexprheumatol/2le8p4

Cited by 2 publications

(2 citation statements)

References 11 publications

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“…Comparable results have already been reported in two patients with off-protocol IL-2 LD treatments. 27 These data at least ensure the absence of disease aggravation under IL-2 LD , especially in fibrosis which could have been a justified fear due to a risk of elevation in TGF-β, a fibrotic cytokine. All these clinical data are, however, collected from a small number of people and other studies are needed to confirm the clinical efficacy.…”

Section: Discussionmentioning

confidence: 93%

Induction of regulatory T cells and efficacy of low-dose interleukin-2 in systemic sclerosis: interventional open-label phase 1–phase 2a study

Barde,

Lorenzon,

Vicaut

et al. 2024

RMD Open

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BackgroundSystemic sclerosis (SSc) is a chronic autoimmune disease, with impaired immune response, increased fibrosis and endothelial dysfunction. Regulatory T cells (Tregs), which are essential to control inflammation, tissue repair and autoimmunity, have a decreased frequency and impaired function in SSc patients. Low-dose interleukin-2 (IL-2LD) can expand and activate Tregs and has, therefore, a therapeutic potential in SSc.ObjectiveWe aimed to assess the safety and biological efficacy of IL-2LDin patients with SSc.MethodsAs part of the TRANSREG open-label phase IIa basket trial in multiple autoimmune diseases, we studied nine patients with SSc without severe organ involvement. Patients received 1 million international units (MIU)/day of IL-2 for 5 days, followed by fortnightly injections for 6 months. Laboratory and clinical evaluations were performed between baseline and month 6.ResultsAt day 8, the primary endpoint (Treg frequency) was reached with a 1.8±0.5-fold increase of Treg levels among CD4+T lymphocytes (p=0.0015). There were no significant changes in effector T cells nor in B cells. IL-2LDwas well tolerated, and no serious adverse events related to treatment occurred. There was a globally stable measurement in the modified Rodnan skin score and Valentini score at month 6. Disease activity and severity measures, the quality of life evaluated by EuroQL-5D-5L and pulmonary function test parameters remained stable during the study period.ConclusionIL-2LDat a dosage of 1 MIU/day safely and selectively activates and expands Tregs. Clinical signs remain stable during the study period. This opens the door to properly powered phase II efficacy trials investigating IL-2LDtherapeutic efficacy in SSc.

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Section: Discussionmentioning

confidence: 93%

Induction of regulatory T cells and efficacy of low-dose interleukin-2 in systemic sclerosis: interventional open-label phase 1–phase 2a study

Barde,

Lorenzon,

Vicaut

et al. 2024

RMD Open

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“…Interleukin 2 (IL2) is a key cytokine for T cell activation and proliferation, and since natural Treg cells express high levels of CD25 (IL2 receptor alpha chain), they are highly sensitive to stimulation via IL2 [10]. This rationale led to various studies demonstrating the restorative effects of lowdose IL2 therapy leading to the expansion of the Treg cell population, attenuation of other immune mediators, and improvement of disease activity in patients suffering from various autoimmune disorders, the phenomenon referred to as immunomodulation [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Low-Dose Interleukin 2 Therapy in Conjunction With Standard Therapy in Patients With Systemic Lupus Erythematosus vs Rheumatoid Arthritis: A Systematic Review

Riaz,

Garg,

Umeano

et al. 2024

Cureus

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This systematic review aims to compare the efficacy and safety of a novel immunotherapy with low-dose interleukin 2 (IL2) across two of the most prevalent autoimmune diseases i.e. systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Contemporary therapeutic practices have not been able to achieve complete remission from these autoimmune disorders. In contrast, low-dose IL2 has shown promise in achieving this therapeutic goal via inducing self-tolerance in patients with autoimmune diseases; however, due to variable irregularities among autoimmune processes of variable diseases, the benefit of low-dose IL2 could not be determined among different autoimmune diseases. Therefore, we conducted a study to compare low-dose IL2 therapy effects on SLE and RA. We systematically screened four databases: PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), PubMed Central (PMC), and Google Scholar. Inclusion and exclusion criteria were implemented. Quality appraisal of studies chosen for the review was done using the Cochrane Risk-of-Bias (RoB) assessment tool for randomized controlled trials, and the Newcastle-Ottawa Scale (NOS) and JBI critical appraisal tool for non-randomized clinical trials. Information was gathered from seven articles: three randomized controlled trials and four non-randomized clinical trials. Our review concluded that low-dose IL2 therapy in conjunction with respective standard therapies for SLE and RA has a higher efficacy and safety profile as compared to standard therapy alone and the therapeutic effects were comparable in both SLE and RA patients treated with low-dose IL2; however, this novel intervention does not seem to have a significant corrective effect on the biomarkers of RA as it does for SLE biomarkers.

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Cohort study of off-label use of low-dose IL-2 therapy for systemic autoimmune diseases

Cited by 2 publications

References 11 publications

Induction of regulatory T cells and efficacy of low-dose interleukin-2 in systemic sclerosis: interventional open-label phase 1–phase 2a study

Induction of regulatory T cells and efficacy of low-dose interleukin-2 in systemic sclerosis: interventional open-label phase 1–phase 2a study

Comparison of Low-Dose Interleukin 2 Therapy in Conjunction With Standard Therapy in Patients With Systemic Lupus Erythematosus vs Rheumatoid Arthritis: A Systematic Review

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