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Could tocilizumab be used in familial Mediterranean fever? A systematic review

Updated: Jan 22

First author : P. Mertz

Review: Rheumatology



Could tocilizumab be used in Familial Mediterranean Fever?
Could tocilizumab be used in Familial Mediterranean Fever ?

Abstract:


Introduction:

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease characterized by recurrent fever and serosal inflammation. Although colchicine is the primary treatment, around 10% of FMF patients do not respond to it, necessitating alternative therapies. Biologic treatments, such as IL-1β, TNF-α and IL-6 inhibitors, have been considered. However, the accessibility and cost of IL-1β inhibitors may limit their use in certain regions. Tocilizumab (TCZ), an IL-6 receptor inhibitor, offers an alternative, but its efficacy in FMF is not well-documented.


Results:

After selection, 14 articles were included: two double-blind RCTs, two retrospective studies and 10 case reports. Multicentre double-blind RCTs reported mixed results in FMF patients without AA amyloidosis due to genetic/classification heterogeneity of the available studies, possible misdiagnosed FMF patients and study design. Retrospective studies suggest that TCZ may benefit FMF patients with established renal AA amyloidosis, potentially preventing progression and managing flares more effectively. TCZ showed a safe profile with no specific adverse events, but data on its use during pregnancy or breastfeeding are lacking. There was no available data on the use of TCZ in paediatric FMF.


Conclusion:

This review summarizes the current state of research, safety and efficacy of TCZ in FMF. While IL1β inhibitors remain the first choice for colchicine-resistant or intolerant FMF patients, TCZ might be of interest in some selected FMF patients with established AA amyloidosis and resistance to colchicine and interleukin 1 inhibitors.




Waldenstrom macroglobulinaemia with AA amyloidosis reveals a B-cell-restricted NLRP2 variant

First author: Terré et al.

Link to article: DOI: 10.1111/bjh.19383


Waldenstrom macroglobulinaemia with AA amyloidosis

Summary

Waldenström macroglobulinemia (WM) is a rare malignant hematopathy characterized by lymphoplasmacytic lymphoma (LPL) secreting IgM. Some patients with WM exhibit chronic inflammation, sometimes complicated by AA amyloidosis, which involves the deposition of insoluble fibrils derived from serum amyloid A (SAA) protein. However, the underlying mechanism of this inflammation remains poorly understood.


We report the case of an 86-year-old female patient with WM complicated by AA amyloidosis. Whole-exome sequencing (WES) revealed a somatic mutation in NLRP2 restricted to B cells. We investigated the functional consequences of this mutation.


The analyses showed that the NLRP2 p.Asp121Gly mutation leads to a reduction in ASC aggregation, a marker of inflammasome activation. In a WM model, the loss of NLRP2 resulted in an increased secretion of CCL-5, a cytokine promoting IL-6 production by stromal cells. IL-6 is a key factor in the induction of SAA, and our results suggest that the NLRP2 mutation may have contributed to the development of AA amyloidosis in this patient.


These findings highlight the importance of somatic mutations in inflammatory regulation and the need for further studies to clarify the role of NLRP2 in the pathophysiology of inflammatory WM (IWM).





Acute tubulointerstitial nephritis and renal amyloidosis: A rare complication of Atezolizumab

Updated: Dec 11, 2024

First author: Naqib Ullah

Journal: Cureus

Reference : DOI : 10.7759/cureus.49533


Article sur Néphrite tubulointerstitielle aiguë et amylose rénale

Introduction:

Lung cancer is the second most common malignancy. The two types of lung cancer are small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Among current treatments, anti-PD-1 or anti-PD-L1 agents (checkpoint inhibitors (PKIs): pembrolizumab and atezolizumab) represent adjuvant therapy in lung cancer. The most frequently reported adverse events with ICPs are diarrhea, pneumopathy and drug-induced hepatitis.


The authors report here the case of a 70-year-old man who received Atezolizumab as adjuvant therapy and developed nephrotic-like proteinuria, revealing AA amyloidosis and atezolizumab-induced interstitial nephritis.



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