Is Th17-Targeted Therapy Effective in Systemic Lupus Erythematosus?

Petrić, Marin; Radić, Mislav

doi:10.3390/cimb45050275

Cited by 9 publications

(2 citation statements)

References 107 publications

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“…Secukinumab was administered to a female patient with psoriasis and refractory lupus nephritis with beneficial effects [180]. Secukinumab is being evaluated for the treatment of active lupus nephritis [181].…”

Section: Secukinumabmentioning

confidence: 99%

Current Treatment Approach, Emerging Therapies and New Horizons in Systemic Lupus Erythematosus

Athanassiou

2023

Life

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Systemic lupus erythematosus (SLE), the prototype of systemic autoimmune diseases is characterized by extreme heterogeneity with a variable clinical course. Renal involvement may be observed and affects the outcome. Hydroxychloroquine should be administered to every lupus patient irrespective of organ involvement. Conventional immunosuppressive therapy includes corticosteroids, methotrexate, cyclophosphamide, mycophenolate mofetil, azathioprine, cyclosporine and tacrolimus. However, despite conventional immunosuppressive treatment, flares occur and broad immunosuppression is accompanied by multiple side effects. Flare occurrence, target organ involvement, side effects of broad immunosuppression and increased knowledge of the pathogenetic mechanisms involved in SLE pathogenesis as well as the availability of biologic agents has led to the application of biologic agents in SLE management. Biologic agents targeting various pathogenetic paths have been applied. B cell targeting agents have been used successfully. Belimumab, a B cell targeting agent, has been approved for the treatment of SLE. Rituximab, an anti-CD20 targeting agent is also used in SLE. Anifrolumab, an interferon I receptor-targeting agent has beneficial effects on SLE. In conclusion, biologic treatment is applied in SLE and should be further evaluated with the aim of a good treatment response and a significant improvement in quality of life.

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Section: Secukinumabmentioning

confidence: 99%

Current Treatment Approach, Emerging Therapies and New Horizons in Systemic Lupus Erythematosus

Athanassiou

2023

Life

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“…It plays an important role in pathogenetic processes in some autoimmune and allergic diseases, such as psoriatic arthritis, spondylarthritis (SpA), and lupus erythematosus. 1 Anti-IL17 therapy, including monoclonal antibodies directed at IL-17 or the IL-17 receptor (IL-17R), has been approved for psoriasis because of its fast onset, robust response, and acceptable safety profile. 2 Secukinumab, an IL-17 antagonist, has strong efficacy and safety in treating moderate-to-severe psoriasis (Ps).…”

Section: Introductionmentioning

confidence: 99%

Membranous lupus nephritis secondary to secukinumab therapy: A case report and literature review

Zhou,

2024

Lupus

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The interleukin (IL)-17 axis is involved in many inflammatory and autoimmune diseases. Secukinumab, an IL-17 inhibitor, has been approved for psoriasis treatment. There are accumulating cases of lupus erythematosus induced by IL-17 inhibition. Lupus nephritis after IL-17 inhibition has not been reported. We report the case of a 57-year-old man who developed membranous lupus nephritis after secukinumab treatment for psoriasis. Anti-SSA and PM-Scl antibodies were positive. dsDNA, anti-Smith, and anti-histone antibodies were negative, and serum complement was low. Secukinumab was discontinued, while tacrolimus was initiated, subsequently switched to cyclosporin, belimumab, glucocorticosteroid, and hydroxychloroquine with a good response. The relationship between lupus erythematosus and IL-17 inhibition requires further research.

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Serum IL-17 and TNFα as prognostic biomarkers in systemic sclerosis patients: a prospective study

Kosałka-Węgiel,

Lichołai,

Pacholczak-Madej

et al. 2023

Rheumatol Int

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Recent reports have demonstrated that endothelial injury is critical in the pathogenesis of systemic sclerosis (SSc) and is associated with increased levels of circulating inflammatory biomarkers. This study aims to analyze the serum concentrations of selected cytokines and evaluate their relationship with SSc clinics and the long-term course of the disease. This study included 43 SSc patients and 24 matched healthy controls. In both groups, we measured serum levels of inflammatory cytokines related to the inflammatory response, such as tumor necrosis factor (TNF)α, interferon (IFN)γ, interleukin (IL)-4, IL-6, IL-10, and IL-17, and fibroblast activation protein (FAP). Additionally, in SSc patients, we evaluated the presence of four single nucleotide polymorphisms (SNPs) located in the promotor region of the TNFA gene, namely rs361525, rs1800629, rs1799964, and rs1799724, which might be related to increased TNFα concentrations. The main aim consisted of associating inflammatory cytokines with (1) clinical disease characteristics and (2) longitudinal observation of survival and cancer prevalence. SSc patients were characterized by a 17% increase in serum TNFα. There was no other difference in serum cytokines between the studied groups and diffuse vs. limited SSc patients. As expected, evaluated serum cytokines correlated with inflammatory biomarkers (e.g., IL-6 and C-reactive protein). Interestingly, patients with higher IL-17 had decreased left ventricle ejection fraction. During the median 5-year follow-up, we recorded four cases of neoplastic diseases (lung cancer in two cases, squamous cell carcinoma of unknown origin, and breast cancer with concomitant multiple myeloma) and nine deaths. The causes of death included lung cancer (n = 2), renal crisis (n = 1), multiple-organ failure (n = 1), and unknown reasons in five cases. Surprisingly, higher TNFα was associated with an increased cancer prevalence, while elevated IL-17 with death risk in the follow-up. Furthermore, the AG rs361525 genotype referred to higher TNFα levels than GG carriers. Both AG rs361525 and CT rs1799964 genotypes were associated with increased cancer risk. Higher serum concentrations of TNFα characterize the SSc patients, with the highest values associated with cancer. On the other hand, increased IL-17 in peripheral blood might predict poor SSc prognosis. Further research is needed to validate these findings.

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Is Th17-Targeted Therapy Effective in Systemic Lupus Erythematosus?

Cited by 9 publications

References 107 publications

Current Treatment Approach, Emerging Therapies and New Horizons in Systemic Lupus Erythematosus

Current Treatment Approach, Emerging Therapies and New Horizons in Systemic Lupus Erythematosus

Membranous lupus nephritis secondary to secukinumab therapy: A case report and literature review

Serum IL-17 and TNFα as prognostic biomarkers in systemic sclerosis patients: a prospective study

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