Clinical benefits of TNF‐α inhibitors in Chinese adult patients with NLRP3‐associated autoinflammatory disease

Abstract

Background Nucleotide‐binding oligomerization domain‐like receptor family, pyrin domain containing 3 (NLRP3)‐associated autoinflammatory disease (NLRP3‐AID) is a rare, heterogeneous disease entity associated with mutations in NLRP3. Biologic therapy for NLRP3‐AID yields diverse results. Objectives We aimed to evaluate the clinical features and outcomes of Chinese adult patients with NLRP3‐AID who were treated with tumour necrosis factor (TNF)‐α inhibitors. Methods Five patients with NLRP3‐AID were diagnosed and treated with TNF‐α inhibitors at Peking Union Medical College Hospital between 2017 and 2020 and were followed up for 6 to 12 months. All patients were systematically studied for treatment outcomes, including clinical manifestations and inflammatory markers. Results All five adult NLRP3‐AID patients were Chinese Han, and four patients were males. The mean age at disease onset was 4.2 ± 4.1 years, and the mean time of diagnosis delay was 19.8 ± 6 years. All patients received TNF‐α inhibitors with or without methotrexate/prednisone. During follow‐up, all patients achieved remarkable clinical remission of skin lesions and polyarthritis and showed improvements in acute‐phase reactants, inflammatory cytokines, patient visual analogue scale, physician global assessment and 36‐item Short Form (SF‐36). Conclusions Early diagnosis and effective therapy for NLRP3‐AID are essential for avoiding irreversible organ damage. TNF‐α inhibitors might serve as a therapeutic alternative for patients with NLRP3‐AID who have unsatisfactory responses or no access to interleukin‐1 inhibitors.

The genetic and clinical characteristics and effects of Canakinumab on cryopyrin-associated periodic syndrome: a large pediatric cohort study from China

“… Q705K did not describe other symptoms except for neurological involvement ( 29 ). K129R, Q703K, V70M, P38S, and D29V did not describe neurological involvement, so they were excluded from the denominator ( 30 ).…”

“…The reported CAPS were less than 100 until now in China (26,27,(29)(30)(31)(32)(33)(34)(35). The number of reported cases is very limited compared with the large number of potential CAPS patients in China.…”

“…NLRP3 novel mutations and comparison with pediatric CAPS, pediatric compared with adult Chinese, and Western CAPS. describe other symptoms except for neurological involvement(29). K129R, Q703K, V70M, P38S, and D29V did not describe neurological involvement, so they were excluded from the denominator(30).…”

Single-cell transcriptomic analysis in two patients with rare systemic autoinflammatory diseases treated with anti-TNF therapy

“…Some studies have reported increased NFkB activation and defective autophagy as potential pathogenic mechanisms (16)(17)(18). In our previous study, we observed a good response to TNF inhibitors in CAPS patients (19). Whether there are other pathways involved in the pathogenesis of SAIDs, and what the underlying mechanisms are in response to TNF blocking therapy, remain to be elucidated.…”

Single-cell Transcriptomic Analysis of Systemic Autoinflammatory Diseases with Anti-TNFα Therapy

“…Some studies have reported increased NFκB activation and defective autophagy as potential pathogenic mechanisms (Bachetti et al, 2013; Hua et al, 2018; Nedjai et al, 2008). In our previous study, we observed a good response to TNFα inhibitors in CAPS patients (Wu et al, 2021). Whether there are other pathways involved in the pathogenesis of SAIDs, and what the underlying mechanisms are in response to TNFα blocking therapy, remain to be elucidated.…”