C-reactive protein is more suitable than Serum Amyloid A to monitor crises and attack-free periods in Systemic Auto-Inflammatory Diseases

Abstract

Background: With their broad presentations and no global biomarker to discriminate crises and attack-free periods, Systemic Auto-Inflammatory Diseases (SAID) are difficult to manage. This study assessed Serum Amyloid A (SAA), C-reactive protein (CRP) and serum calprotectin as potential biomarkers to monitor patients with SAID.

Method: SAA (already studied in Familial Mediterranean Fever (FMF)), CRP and serum calprotectin were measured on SAID adult patients from Juvenile Inflammatory Rheumatism (JIR) cohort during their follow-up visits between 2020 and 2022. Crises and attack-free periods were clinically determined.

Results: 96 measures, mainly from FMF (43 %) and Unclassified SAID (USAID) (37 %) patients were included. Using ROC curves, a threshold with sensitivity and specificity of/over 75 % was determined for SAA (9 mg/L) and CRP (9 mg/L) but not for serum calprotectin, not investigated further. With this threshold, the results were similar in FMF and USAID patients' subgroups. SAA and CRP showed a positive correlation with crises and attack-free periods in SAID patients (r = 0.4796, p < 0.001 and r = 0.5525, p < 0.001, respectively) as in FMF and USAID patients, with no significant difference between both markers in diagnosis value and ROC curves Area Under Curve (AUC) (p = 0.32). Only the CRP results were not influenced by obesity.

Conclusion: SAA and CRP can discriminate crisis and attack-free periods in our cohort of SAID patients mainly composed of FMF and USAID patients. However, only CRP can be used regardless of body mass index. It is the first report of common biomarkers for all SAID, including USAID patients, with CRP widely accessible in routine worldwide.

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Canakinumab treatment real world evidence in 3 monogenic periodic fever syndromes in 2009-2022: an interim analysis using the French JIR cohort database

First author: Isabelle Koné-Paut et al.

Link to article: DOI: 10.1186/s13075-024-03316-7

Abstract

Background: Our study aimed to provide real-world evidence on the treatment patterns, effectiveness and safety of canakinumab in France in 3 monogenic periodic fever syndrome: Familial Mediterranean Fever (FMF), Mevalonate Kinase Deficiency (MKD), and Tumor necrosis factor Receptor Associated Periodic Syndrome (TRAPS).

Methods: This study used the JIR cohort, a multicentre international registry created in 2013 to collect data on patients with juvenile inflammatory rheumatic diseases. French patients diagnosed with FMF, MKD or TRAPS and treated with canakinumab were included in this study.

Results: 31 FMF, 26 MKD and 7 TRAPS patients received canakinumab during the study period. Most of them initiated canakinumab at the recommended dose of 2 mg/kg or 150 mg, but less than half of FMF and MKD patients initiated it at the recommended frequency (every 4 weeks). Two years after initiation, the rate of patients still on treatment was 78.1% in FMF, 73.7% in MKD, and 85.7% in TRAPS patients. While the dose per injection remained globally the same over the course of the treatment, some adjustments of the dose intervals were observed. Six patients had a severe adverse event reported. Of those, three were possibly related to canakinumab.

Conclusion: This interim analysis showed a good maintenance of canakinumab treatment 2 years after initiation and confirmed its safety profile in real-life practice in France in patients diagnosed with FMF, MKD and TRAPS. The high variety of dose and interval combinations observed in canakinumab treated patients let suppose that physicians adapt the posology to individual situations rather than a fixed treatment plan.

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Frequency of AA amyloidosis has decreased in Behçet’s syndrome: a retrospective study with long-term follow-up and a systematic review: Amyloidosis in Behçet’s syndrome

First author : G Karatemiz

Review : Rheumatology

Reference :  DOI :  doi.org/10.1093/rheumatology/keac223

Link to article https://academic.oup.com/rheumatology/article/62/1/9/6601421

Introduction:

Inflammatory rheumatic diseases are a classic cause of inflammatory amyloidosis (AA). Behçet's disease is a multi-systemic vasculitis that affects vessels of all calibres. Although uncommon in Behçet's disease, AA amyloidosis is at high risk of mortality and is one of the main causes of renal failure in Behçet's disease. The authors' aim was to determine the frequency of AA amyloidosis in patients with Behçet's disease, and identify clinical and therapeutic demographics.

Methods:

Patients with Behçet's disease complicating with AA amyloidosis in Turkey were included. The primary endpoints were end-stage renal disease and death. The prevalence of AA amyloidosis was estimated separately for patients registered between 1976 and 2000 and those registered between 2001 and 2017, to determine whether there was a change in frequency.

A systematic review of the literature on cases of AA amyloidosis complicating Behçet's disease accompanied this study.

Results:

Between 1976 and 2017, a cohort of patients with Behçet's disease (n=9410) was followed of whom, 27 (0.29%) developed AA amyloidosis.

Between 1976 and 2000, a cohort of 3,820 patients with Behçet's disease was followed; 24 patients (0.62%) developed AA amyloidosis.

Between 2001 and 2017, of the 5590 patients followed for Behçet's disease, 3 developed AA amyloidosis (0.054%).

The incidence of AA amyloidosis increased from 0.62% to 0.054% (P < 0.0001).

Co-morbidities that may be associated with amyloidosis were tuberculosis (n= 2), FMF

FMF (n=1) and spondyloarthritis (n=1). MEFV gene sequencing had been performed in 2 patients showing no pathogenic variant, and one of them was heterozygous for the M680I mutation.

Prior to the diagnosis of AA amyloidosis, 19 patients (70%) were on colchicine, 15 patients were on immunosuppressants and 2 on corticosteroids only. At the time of amyloidosis diagnosis, 12 patients were off treatment, 8 were using an immunosuppressant (5 AZA, 2 CYC and 1 MTX), and 2 were using CS only.

Outcome:

Fourteen patients (52%) died after a median follow-up of 3 years (IQR: 7.75), 3 were lost to follow-up and 10 (37%) were still alive after a median follow-up of 11 years

(IQR: 16). The reasons for death were infections in 5 cases, complications related to end-stage renal failure in 5 cases, subarachnoid haemorrhage, gastric adenocarcinoma, cirrhosis associated with amyloidosis and iatrogenic intestinal perforation in one case each. Nine (64%) of the 14 patients who died had developed end-stage renal disease (ESRD).

Overall, 15/27 patients (55.5%) developed ESRD after a median follow-up of 3.5 years (IQR: 5.25) after diagnosis of AA amyloidosis. Five patients underwent renal transplantation.

A systematic review of the literature revealed 82 cases in 42 publications. The main characteristics of the patients were a predominance of males and a high frequency of vascular involvement. One third of patients died within 6 months of diagnosis of AA amyloidosis (table 1).

Discussion and conclusion:

According to the results of this study, the frequency of AA amyloidosis in patients with Behçet's disease appears to be decreasing. Male patients with major organ involvement, particularly vascular involvement, appear to be more likely to develop AA amyloidosis. Although AA amyloidosis rarely complicates Behçet's disease, its occurrence is observed in younger patients and it appears to worsen the overall prognosis of the disease.

Caractéristiques démographiques et cliniques de nos 27 patients BS et de ceux identifiés par la revue systématique

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