Treatment Of Familial Mediterranean Fever Research Articles

The usefulness and reliability of English-language YouTube videos as a source of knowledge for patients with familial Mediterranean fever.

YouTube is increasingly being used as an educational tool and is a substantial source of information. This study aimed to assess the quality of the most viewed YouTube videos pertaining to familial Mediterranean fever (FMF). A search on YouTube was conducted on January 13, 2022, using the keywords: "familial Mediterranean fever treatment," "familial Mediterranean fever colchicine," and "familial Mediterranean fever colchicine opacalcium." Two rheumatologists independently evaluated the relevance and accuracy of the videos. Redundant or irrelevant videos were excluded. The educational value of YouTube videos was assessed using the Global Quality Scale (GQS). Comparative analyses of video parameters across different cohorts were performed. To assess the reliability and quality of the videos, a modified version of the DISCERN scale and the GQS were employed. Out of the 59 videos reviewed, 43 (72.9%) were of high quality, 10 (16.9%) were of medium quality, and 6 (10.2%) were of low quality. Upon comparing parameters among groups, no significant disparities were observed in terms of daily views, daily favorites, daily dislikes, or daily comments (p>0.05). GQS scores for usefulness and modified DISCERN scores showed significant differences among groups (p<0.001). Additionally, both GQS and modified DISCERN scores exhibited moderately negative correlations (r=-.450 and r=-.474, respectively) and high statistical significance (p<0.001 for both) with utility assessment. YouTube is a valuable repository of high-quality videos for FMF patients. Healthcare providers should guide their patients to high-quality video sources to supplement their educational material.

Drug metabolism and inflammation related distinct miRNA signature of colchicine resistant familial Mediterranean fever patients

ObjectiveColchicine is the primary treatment for familial Mediterranean fever (FMF). Although colchicine is safe and effective in FMF patients, around 5–10% of patients show resistance to the drug. This study investigates the possibility of a link between colchicine resistance and the distinct miRNA profiles in colchicine resistant FMF patients. MethodsDifferentially expressed miRNAs in colchicine resistant FMF patients were detected by Affymetrix 4.0 miRNA array analysis. These miRNAs were then categorized based on the role of their target genes in drug metabolism and inflammation related pathways. qRT-PCR was used to validate candidate miRNAs selected by Enrichr, a gene enrichment analysis system based on the relevance of possible target genes in drug metabolism pathways. Expression levels of these miRNAs’ potential target genes were investigated by qRT-PCR. Then, a colchicine resistant hepatoblastoma cell line (HEPG2) was established, and the differentially expressed miRNAs and genes identified in patients were also analyzed in this colchicine-resistant cell line. Results25 differentially expressed miRNAs were detected in colchicine resistant FMF patients. miR-183-5p, miR-15b-5p, miR-505-5p, and miR-125a-5p were identified to be associated with drug resistance and inflammatory pathways and thus chosen for further validation. miR-183-5p, miR-15b-5p, miR-505-5p miRNAs showed significantly differential expression in qRT-PCR.NFKB1, NR3C1, PPARα – drug absorption, distribution, metabolism, and excretion (ADME) genes were predicted to be targeted by these miRNAs. Among these targets, NFKB1 and NR3C1 were differentially over expressed in colchicine resistant FMF patients. These findings were validated in the colchicine resistant hepatoblastoma cell line (HEPG2). ConclusionThis is the first study evaluating the role of miRNAs in colchicine resistant patients with FMF. Their differential expression may result in resistance to standard colchicine treatment by affecting the expression of genes that take place in drug absorption, distribution, metabolism, and excretion (ADME) or nuclear receptors that regulate ADME genes, thus potentially playing a role in both drug metabolism and inflammation.

Familial Mediterranean Fever-Related Amyloidosis in Turkey: A Need for a Familial Mediterranean Fever Registry.

Amyloidosis has been well known since Rudolph Virchow named the condition in the 19th century. Most physicians were aware of the association between amyloidosis to chronic suppurative conditions and multiple myeloma. However, familial Mediterranean fever, although probably as ancient as the Galenic era, was appropriately identified only in the 21st century. The nomenclature was variable throughout history, but the name "FMF" has been universally adopted since the report from Heller and colleagues in 1958. In 1967, Sokmen and Ozdemir of Ankara University published a report on 194 patients, of whom 64 had amyloidosis. Familial Mediterranean fever constituted the cause in half of the cases. Goldfinger and Ozkan demonstrated efficacy of colchicine for treatment of familial Mediterranean fever in 1972, and further studies revealed that colchicine is also efficient for prevention of amyloidosis. However, since then, several single-center and multicenter amyloid A amyloidosis studies from Turkey have been published. Almost invariably, familial Mediterranean fever is the most common cause of systemic amyloidosis. No downward trends in percentages have been observed. Recent studies have shown that cases of amyloidosis in patients with familial Mediterranean fever are decreasing. Also, cases of amyloidosis in conjunction with suppurative conditions are on the decrease worldwide. However, according to registry data from the Turkish Society of Nephrology, the percentage of incident hemodialysis patients with amyloidosis is not decreasing. The question arises: Why is a complication that is 98% preventable still causing end-stage renal disease? We believe the lack of a stable and comprehensive registry for familial Mediterranean fever, including associated cases of amyloidosis, is the reason we cannot properly answer this question. In this work, we use a historical approach to present why a familial Mediterranean fever registry is direly needed.

A score for predicting colchicine resistance at the time of diagnosis in familial Mediterranean fever: data from the TURPAID registry.

Colchicine forms the mainstay of treatment in FMF. Approximately 5-10% of FMF patients are colchicine resistant and require anti-IL-1 drugs. We aimed to compare the characteristics of colchicine-resistant and colchicine-responsive patients and to develop a score for predicting colchicine resistance at the time of FMF diagnosis. FMF patients (0-18 years) enrolled in the Turkish Paediatric Autoinflammatory Diseases (TURPAID) registry were included. The predictive score for colchicine resistance was developed by using univariate/multivariate regression and receiver operating characteristics analyses. A total of 3445 FMF patients [256 (7.4%) colchicine-resistant and 3189 colchicine-responsive) were included (female:male ratio 1.02; median age at diagnosis 67.4 months). Colchicine-resistant patients had longer, more frequent attacks and were younger at symptom onset and diagnosis (P < 0.05). Fever, erysipelas-like erythema, arthralgia, arthritis, myalgia, abdominal pain, diarrhoea, chest pain, comorbidities, parental consanguinity and homozygosity/compound heterozygosity for exon 10 MEFV mutations were significantly more prevalent among colchicine-resistant than colchicine-responsive patients (P < 0.05). Multivariate logistic regression analysis in the training cohort (n = 2684) showed that age at symptom onset, attack frequency, arthritis, chest pain and having two exon 10 mutations were the strongest predictors of colchicine resistance. The score including these items had a sensitivity of 81.3% and a specificity of 49.1%. In the validation cohort (n = 671), its sensitivity was 93.5% and specificity was 53.8%. We developed a clinician-friendly and practical predictive score that could help us identify FMF patients with a greater risk of colchicine resistance and tailor disease management individually at the time of diagnosis.

The use of Anakinra in a patient with a combination of two autoinflammatory diseases: Familial Mediterranean fever and gout

Along with familial Mediterranean fever (FMF), it is now considered an autoinflammatory disease and gout. The commonality of the basic mechanisms of inflammation underlying the pathogenesis of FMF and gout predetermines the possibility of using similar therapies aimed at stopping and preventing seizures (colchicine and IL-1 inhibitors). A clinical case is presented describing the presence of a combination of FMF and gout in a patient. The patient was prescribed anakinra, which proved to be effective both as a treatment for FMF and gout. The appointment of an IL-1 inhibitor fully justified expectations: already after the first injection of anakinra, the intensity of swelling and pain in the joints decreased in the patient.

Adherence to Colchicine During Pregnancy in Familial Mediterranean Fever Patients: Reasons for Cessation and Outcomes from a Single-Centre Experience

Abstract Objective To evaluate the adherence to colchicine treatment during pregnancy and lactation in our Familial Mediterranean fever (FMF) patients and investigate the reasons for non-adherence and consequences. Methods Adult female FMF patients who were followed up in our rheumatology clinic and had a history of pregnancy after the diagnosis of FMF were consecutively enrolled to this cross-sectional study between November 2021 and June 2022. Only pregnancies occurring after the diagnosis of FMF were evaluated. Patients who did not stop using FMF treatment after pregnancy were considered to adhere to treatment. Results In 50 patients, a total of 88 pregnancies and 58 live births were observed after the diagnosis of FMF. 37 (74%) had at least one completed pregnancy, and 13 (26.0) were pregnant during the study. Among the 37 patients, 34 had at least one live birth. No significant differences were observed when rates of patients with a history of at least one live birth, abortus, Cesarean section (C/S), preterm labor, stillbirth, intrauterine anomaly, congenital malformation and fetal growth retardation were compared between colchicine users and non-users. 60% of the patients adhered to colchicine treatment during pregnancy and 73.4% did so while breastfeeding. The most common reason for colchicine cessation was concerns regarding potential harm to the fetus (70%), followed by the presumption that colchicine is contraindicated in pregnancy (15%) as well as absence of FMF attacks (10%). The most common source of the patients’ opinion was a physician (60%). Conclusions Both patients and attending physicians should be informed to be more adherent to colchicine to avoid adverse outcomes and FMF-related complications.

Budget impact analysis of anakinra in the treatment of familial Mediterranean fever in Italy

ABSTRACT Introduction: Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease that significantly reduces occupational productivity and quality-of-life in affected patients. Italy has an estimated FMF prevalence of 1 in 60,000 people. While colchicine is the primary treatment for FMF, biologics are administered to intolerant and non-responder patients. Anakinra and canakinumab are the only biologics approved and reimbursed for FMF in Italy. Both medicines have demonstrated efficacy in FMF patients yet differ in treatment costs. This study aimed to perform a budget impact analysis (BIA) following anakinra’s reimbursement for FMF treatment, considering pharmaceutical costs from the Italian National Healthcare Service (NHS) perspective. Methods: A ‘Reference scenario’ (all patients treated with canakinumab) was compared to an ‘Alternative scenario’, with increased anakinra market shares. The target population was estimated based on the Italian population, epidemiological and market research data. Drugs costs were estimated based on Summary of Product Characteristics and net ex-factory prices. Sensitivity analyses were implemented to test results’ robustness. Results:The base case analysis showed an overall cumulative expenditure of €30,586,628 for ‘Reference scenario’ and € 16,465,548 for ‘Alternative scenario’. A cumulative savings of €14,121,080 (46.2%) was calculated over 3 years as a result of the reimbursement and increasing uptake of anakinra. The sensitivity analyses, even considering a discount of 50% for canakinumab, confirmed the base case results. Conclusions: Anakinra’s introduction, in FMF treatment, provides a financially sustainable option for Italian patients, with savings increasing according to greater use of anakinra.

The relationship between nutrition, inflammation and colchicine resistance in familial Mediterranean fever

Aim: Familial Mediterranean fever (FMF) is an autoinflammatory and genetic disease associated with chronic inflammation. Colchicine is the gold standard treatment for FMF, although some patients respond partially. Factors such as heavy exercise, cold exposure, stress, recent infection or surgery have been associated with the occurrence of attacks. Recently, nutrition is thought to be involved in the pathogenesis of autoimmune and autoinflammatory diseases. Therefore, we aimed to investigate the relationship between nutrition, inflammation and colchicine resistance by considering the nutritional status of FMF patients.&#x0D; Material and Method: The study included 59 patients and 67 healthy individuals who were matched for gender, age and body mass index (BMI). Clinical, anthropometric, and biochemical measurements were obtained. Three-days, 24-hour diet records were recorded in the nutrient database program (BeBiS software program), the amounts of macro and micronutrient contents were determined and the Diet Inflammatory Index (DII) score was calculated and compared between groups.&#x0D; Results: Statistically, the diets of FMF patients were found to be higher in omega-6, carbohydrate percentage and salt content, and lower in terms of lactose, fat percentage, monounsaturated fatty acids, retinol and biotin compared to controls. There was no correlation between DII and acute phase reactants and colchicine dose.&#x0D; Conclusion: The course of FMF can be affected by environmental factors, as well as its genetic background. Nutrition is a new and interesting topic in this regard and may contribute to inflammation and disease activity in FMF patients.

Tocilizumab for the Treatment of Familial Mediterranean Fever-A Randomized, Double-Blind, Placebo-Controlled Phase II Study.

Background: The purpose of this trial was to evaluate the effectiveness and safety of the IL-6 receptor antibody Tocilizumab (TCZ) in the treatment of Familial Mediterranean Fever (FMF). Methods: This was a randomized, double-blinded, placebo-controlled phase II trial in adult patients with active FMF and an inadequate response or intolerance to colchicine (crFMF). The physician’s global assessment of disease activity (PGA), based on a five-point scale for six symptoms, was used as a clinical score, which had to be >2 at screening, together with elevated c-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) and serum amyloid A (SAA) levels, to be eligible for inclusion. Patients were randomized 1:1 to either receive monthly TCZ or a placebo over a period of 24 weeks. The primary endpoint was the number of patients achieving an adequate response to treatment at week 16, defined as a PGA of ≤2 and normalized ESR or CRP and normalized SAA. Results: We randomized 25 patients with a median age of 31 years. At week 16, an adequate treatment response was achieved by two patients in the TCZ and none of the patients in the placebo arm (p = 0.089). SAA levels normalized with TCZ, but not with the placebo (p = 0.015). Conclusion: In this first randomized, placebo-controlled study in patients with active crFMF, more patients in the TCZ arm experienced a response to treatment in comparison to those receiving the placebo. As the prevention of amyloidosis is a major treatment goal in FMF, the normalization of SAA in TCZ-treated patients is essential. These findings have to be confirmed in a larger trial.

The Characteristics of Pediatric Patients with Familial Mediterranean Fever Treated with Anti-Interleukin-1 Treatment.

Objective:Interleukin-1 inhibitors are effective agents used in colchicine resistance or intolerance during the treatment of familial Mediterranean fever. This study aims to review the characteristics of patients treated with interleukin-1 inhibitors and their long-term follow-up in a large pediatric cohort of familial Mediterranean fever patients.Materials and Methods:The study was conducted in a pediatric rheumatology reference center. The patients treated with interleukin-1 inhibitors for at least 6 months were included and compared to other patients with familial Mediterranean fever. Clinical and laboratory characteristics of the cohort were recorded.Results:Among 542 patients with familial Mediterranean fever, 6.1% (n = 33) were treated with interleukin-1 inhibitors. Colchicine resistance was the reason in 82.8% and renal amyloidosis in 17.2% of the patients. Patients with interleukin-1 inhibitors had earlier disease onset and higher frequencies of acute arthritis, chest pain, and erysipelas-like erythema with pathogenic exon 10 mutations of the MEFV gene (all P < .04). All patients diagnosed with renal amyloidosis also received interleukin-1 inhibitors. Six patients were switched from anakinra to canakinumab or vice versa to control ongoing disease activity. Attack frequency was reduced in all patients. Conclusion:Interleukin-1 inhibitors are used in a relatively small number of pediatric patients with familial Mediterranean fever. Patients presenting with earlier disease onset, acute arthritis, chest pain, and erysipelas-like erythema and carrying pathogenic exon 10 mutations of the MEFV gene may show a higher need for interleukin-1 inhibitors. In pediatric familial Mediterranean fever patients who are resistant to colchicine, interleukin-1 inhibitors seem to be highly effective agents.

A single‐center COVID‐19 vaccine experience with CoronaVac and BNT162b2 in familial Mediterranean fever patients

AimTo determine frequency of adverse events and attacks related to vaccination in recipients of CoronaVac and BNT162b2 in familial Mediterranean fever (FMF) patients, and to search whether history of prior COVID‐19 or a booster dose increases occurrence of adverse events/attacks.MethodsFMF patients were surveyed for administration of any COVID‐19 vaccine and vaccine‐related adverse events or FMF attacks. Demographic, clinical, vaccine‐related data, history of COVID‐19 infection before or after vaccination, adherence to FMF treatment during vaccination were collected.ResultsA total of 161 vaccinated FMF patients were included. Ninety‐three patients out of 161 had reported suffering from an adverse event/attack after a vaccine dose. There were 54.7% of BNT162b2 recipients who reported any adverse event after any vaccine dose in comparison to 29.9% of CoronaVac recipients (P < .001). There were 22.2% of BNT162b2 recipients who reported suffering from a FMF attack within 1 month after vaccination in comparison to 19.4% of CoronaVac recipients (P = .653). When patients with or without adverse event/attack were compared, no significant differences were observed in means of demographics, comorbid diseases, disease duration, total vaccine doses, or treatments adhered to for FMF. Rates of adverse events/attacks were similar between patients with and without prior COVID‐19. In booster recipients, adverse events/attacks were most frequent after the booster dose.ConclusionsA considerable number of FMF patients suffered from vaccine‐related adverse events/attacks, particularly with BNT162b2. No serious events or mortalities due to vaccination were detected. Demographics, clinical characteristics and prior history of vaccination did not significantly affect these results. We observed an increased rate of adverse events/attacks with booster dose administration.

The Preferential Use of Anakinra in Various Settings of FMF: A Review Applied to an Updated Treatment-Related Perspective of the Disease.

Familial Mediterranean fever (FMF), the most frequent monogenic autoinflammatory disease, is manifested with recurrent and chronic inflammation and amyloid A (AA) amyloidosis, driven by overproduction of interleukin 1 (IL-1) through an activated pyrin inflammasome. Consequently, non-responsiveness to colchicine, the cornerstone of FMF treatment, is nowadays addressed by IL-1- blockers. Each of the two IL-1 blockers currently used in FMF, anakinra and canakinumab, has its own merits for FMF care. Here we focus on anakinra, a recombinant form of the naturally occurring IL-1 receptor antagonist, and explore the literature by using PubMed regarding the utility of anakinra in certain conditions of FMF. Occasionally we enrich published data with our own experience. To facilitate insights to anakinra role, the paper briefs some clinical, genetic, pathogenetic, and management aspects of FMF. The clinical settings of FMF covered in this review include colchicine resistance, AA amyloidosis, renal transplantation, protracted febrile myalgia, on- demand use, leg pain, arthritis, temporary suspension of colchicine, pediatric patients, and pregnancy and lactation. In many of these instances, either because of safety concerns or a necessity for only transient and short-term use, anakinra, due to its short half-life, is the preferred IL-1 blocker.

Down-regulated Th17 cells in a patient with familial Mediterranean fever associated with amyloid A amyloidosis in the treatment of canakinumab.

Autoinflammatory diseases are innate immune-mediated inflammatory disorders, unlike autoimmune diseases, which are characterised by abnormalities in adoptive immunity, although autoimmune and autoinflammatory diseases have certain similar clinical features. Familial Mediterranean fever (FMF), the most common monogenic autoinflammatory disease, is associated with mutations in the MEFV gene that encodes pyrin, which results in inflammasome activation and uncontrolled production of interleukin (IL)-1β. Regular use of colchicine, the primary drug for FMF treatment, prevents febrile attacks and reduces the long-term risk of subsequent complications of amyloid A (AA) amyloidosis. However, a minority of FMF patients develop colchicine resistance, and anti-IL-1β treatment with canakinumab, which is a genetically modified human IgG subclass type 1 (IgG1) monoclonal antibody specific for human IL-1β, was beneficial in inhibiting inflammation in such patients. Here, we present a patient with FMF associated with AA amyloidosis, who was treated with canakinumab and demonstrated down-regulated Th17 cells and activated Th17 cells (from 21.4% to 12.8%, and from 1.45% to 0.83%, respectively) in peripheral blood, as shown by immunophenotyping via multicolour flow cytometry and by disease activity and improved laboratory inflammatory surrogate markers-C-reactive protein (CRP) and serum AA protein (SAA). CRP had values within normal limits, but SAA did not (Spearman's rank correlation coefficient; ρ = 0.133). We report that SAA and IL-1β may differentiate Th17 cells from CD4+-naïve T cells, and we discuss interactions between autoinflammation and autoimmunity as a model based on this case, through modes of action with IL-1β and SAA. This report is the first demonstrating that an IL-1β antagonist may reduce Th17 cells in FMF as a therapeutic option.

The Effects of Colchicine on the Histopathological Findings of Celiac Disease During Familial Mediterranean Fever Treatment.

Familial mediterranean fever (FMF) and Celiac Disease (CD) are both autoinflammatory and autoimmune diseases with common clinical features affecting the gastrointestinal system. Familial mediterranean fever may coexist with CD. Inflammatory cells and cytokines are up-regulated within the intestinal mucosa of patients with CD. In this perspective, lymphocyte infiltration to the lamina propria of the small intestinal mucosa is a critical pathological sign. In the present study, we aimed to find out whether the treatment of an FMF patient with colchicine affects the pathological signs of concomitant developed CD on the same patient. We retrospectively reviewed the medical records of 147 patients with FMF who were followed up in our center between 2015 and 2020. Of the 147 patients with FMF, 3 patients also had CD. In this report, we presented these 3 cases. The findings obtained in this study suggest that pathological findings may be misinterpreted in autoimmune diseases, such as CD, when patients administer anti-inflammatory treatments, such as colchicine.

Diagnosis and treatment of familial Mediterranean fever (periodic disease)

Diagnosis and treatment of familial Mediterranean fever (periodic disease)

Abstracts from the ISSAID 2021 Periodic Congress

Abstracts from the ISSAID 2021 Periodic Congress

The Assessment of Selected miRNA Profile in Familial Mediterranean Fever.

Familial Mediterranean fever (FMF) is the most prevalent autoinflammatory disease. Typical findings are recurrent fever attacks with serositis, skin rash, and synovitis. FMF is caused by mutations in the MEFV gene, encoding pyrin protein. Pyrin functions in innate immunity and triggers inflammation via inflammatory mediators' production and acts as the primary regulatory component of the inflammasome. On the other hand, various miRNAs play crucial roles in the pathogenesis of different types of cancers and immune-related and neurodegenerative diseases. However, their association with FMF is still unclear. Therefore, in this study, we assessed the roles of selected thirteen miRNAs associated with immune functions. We recruited genetically diagnosed 28 FMF patients and 28 healthy individuals. The expression profiling of the miRNAs was determined by qRT-PCR and normalized to SNORD61. Our analysis revealed that miR-34a-5p, miR-142-3p, miR-216a-5p, miR-340-5p, miR-429, and miR-582-5p were upregulated, whereas miR-107, miR-569, and miR-1304-5p were downregulated in the FMF patients. Among them, miR-107 was found to be the most remarkable in M694V homozygous mutants compared to other homozygous mutants. During clinical follow-up of the patients with M694V mutation, which is closely related to amyloidosis, evaluation of mir-107 expression might be crucial and suggestive. Our results showed that miRNAs might serve a function in the pathogenesis of FMF. Further studies may provide novel and effective diagnostic and therapeutic agents that target examined miRNAs. Targeting miRNAs in FMF seems to be promising and may yield a new generation of rational therapeutics and diagnostic or monitoring tools enabling FMF treatment.

Dimethylaminoparthenolide (DMAPT) as an alternative approach for treatment of Familial Mediterranean Fever (FMF).

Objective(s): Familial Mediterranean Fever (FMF) is a hereditary auto-inflammatory disorder that is caused by mutations in the Mediterranean fever (MEFV) gene and is associated with an increase in pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and interleukin-18 (IL-18), leading to excess inflammation. Colchicine is a common drug widely used for treatment of FMF attacks, but about 5–15% of the patients show resistance to the regular colchicine treatment. In this study, we used dimethylamino-parthenolide (DMAPT), as a small molecule inhibitor of Nuclear factor-κB (NF-κB), NLR family Pyrin domain containing 3 (NLRP3), and cysteine-aspartic acid protease 1(Caspase-1) on FMF-derived peripheral blood mononuclear cells (PBMCs).Materials and Methods:The effects of DMAPT and colchicine on metabolic activity and apoptosis of FMF-derived PBMCs were evaluated by MTT and Annexin V/PI assays, respectively. Also, the expression levels of NF-κB, NLRP3, MEFV, CASP1, and IL-1β mRNA were investigated using a TaqMan real-time PCR, and the protein levels of IL-1β, IL-18, and IL-37 were assessed via an enzyme-linked immunosorbent assay (ELISA) in LPS/ ATP-stimulated PBMCs.Results:DMAPT decreased the expression levels of NFκB (0.38±0.096, P<0.0001), NLRP3 (0.39±0.12, P<0.001), MEFV (0.384±0.145, P<0.001), CASP1 (0.48±0.13, P=0.0023), and IL-1β (0.09±0.09, P<0.0001) and reduced the secretion levels of IL-1β (8.92±5.3 vs. 149.85±20.92, P<0.0001), IL-18 (135±32.1 vs. 192±22.18, P=0.01), and IL-37 (27.5±6.3 vs. 78.19±14.3, P<0.0001) as compared to untreated cells.Conclusion:Given the obtained results in comparison with previous research, the future clinical development of DMAPT could result in the expansion of new anti-inflammatory therapeutics for FMF disorder.

Amyloidosis and Glomerular Diseases in Familial Mediterranean Fever.

Familial Mediterranean fever (FMF) is a genetic autoinflammatory disease with autosomal recessive transmission, characterized by periodic fever attacks with self-limited serositis. Secondary amyloidosis due to amyloid A renal deposition represents the most fearsome complication in up to 8.6% of patients. Amyloidosis A typically reveals a nephrotic syndrome with a rapid progression to end-stage kidney disease still. It may also involve the cardiovascular system, the gastrointestinal tract and the central nervous system. Other glomerulonephritis may equally affect FMF patients, including vasculitis such as IgA vasculitis and polyarteritis nodosa. A differential diagnosis among different primary and secondary causes of nephrotic syndrome is mandatory to determine the right therapeutic choice for the patients. Early detection of microalbuminuria is the first signal of kidney impairment in FMF, but new markers such as Neutrophil Gelatinase-Associated Lipocalin (NGAL) may radically change renal outcomes. Serum amyloid A protein (SAA) is currently considered a reliable indicator of subclinical inflammation and compliance to therapy. According to new evidence, SAA may also have an active pathogenic role in the regulation of NALP3 inflammasome activity as well as being a predictor of the clinical course of AA amyloidosis. Beyond colchicine, new monoclonal antibodies such as IL-1 inhibitors anakinra and canakinumab, and anti-IL-6 tocilizumab may represent a key in optimizing FMF treatment and prevention or control of AA amyloidosis.

Canakinumab is effective in patients with familial Mediterranean fever resistant and intolerant to the colchicine and/or anakinra treatment.

As an autosomal recessive autoinflammatory disease, treatment of Familial Mediterranean fever (FMF) has still gaps. Clinical studies are proving the safety and efficacy of colchicine in patients with FMF. However, there are very limited data on colchicine-resistant patients treated with canakinumab. This study presents the real-life experience of two rheumatology clinics choosing canakinumab in adult patients with FMF resistant to standard therapy. Treatment-resistant FMF patients with validated diagnoses enrolled from two rheumatology clinics. A special database was generated for the study and patients' demographic characteristics, FMF attack characteristics, adverse events seen during treatment, family history, MediterraneanFeVer (MEFV) mutations, and laboratory results recorded. Patients with missing dates were excluded from the analysis. PRAS score is used to assess the disease activity. A total of thirty colchicine and/or anakinra-resistant patients were enrolled to study. Twenty-one patients were female (70%) and the average disease duration was 21years. The time from colchicine to anakinra was 4.27years and the time to canakinumab was 1.52years. Abdominal pain (100%), fever (93.3%), chest pain (56.7%) were the most prevailed findings. Morning stiffness, myalgia, low back pain, chest pain was the predominant musculoskeletal findings. Median colchicine dose was 2mg/day (min-max 0.5-3mg/day). The most common side effect during anakinra treatment, apart from treatment unresponsiveness, was injection site reactions. Before canakinumab treatment, the mean number of attacks was 8.3 in the 24weeks, 4.33 in the third month of canakinumab treatment, and 1.56 at the last visit (p < 0.001). Also, the mean duration of attacks was 67.20h before canakinumab treatment, this period decreased to 18.27h after six months of canakinumab treatment (p < 0.001). Canakinumab is effective and tolerable to reduce attacks in resistant patients with FMF. Laboratory findings and clinical observation reveals that canakinumab can be another treatment option for colchicine and/or anakinra non-responders. Further studies with larger patients are required to validate recent findings with canakinumab.