Regular Colchicine Treatment Research Articles

Assessment of vascular damage in children and young adults with Familial Mediterranean Fever.

Familial Mediterranean Fever (FMF) is the most frequent autoinflammatory disease. This study aimed to evaluate the risk of subclinical vascular damage in FMF children, and young adults, using both imaging and laboratory tests. Forty-five FMF patients (mean age 14.3 ± 9.5years, 33 children) and 44 healthy controls(mean age 13.3 ± 8.6years, 36 children) were included in the study. The patients were diagnosed according to Tel-Hashomer criteria, were positive for MEFV gene mutation, were treated with colchicine and were evaluated during an attack free-period. The arterial stiffness parameters studied were carotid-femoral pulse wave velocity (PWV), Augmentation Index (Aix), subendocardial viability ratio (SEVR) and carotid intima-media thickness (cIMT). Laboratory parameters, inflammation markers and lipid profile were also evaluated for all participants. There were no significant differences between patients and healthy individuals, as well as in our children population regarding PWV, SEVR, Aix and cIMT. However, significantly higher ESR, CRP and fibrinogen levels were detected in the total population of FMF patients and higher amyloid levels in FMF children, compared to controls. Atherogenic Index of Plasma was significantly higher both in the total patient population and in the subgroup of children, compared to controls. Furthermore, a significant positive correlation between Aix and CRP and a negative correlation between SEVR and ESR became apparent in the pediatric subgroup. Our study demonstrated no significant differences in vascular measurements between FMF patients and controls. The above could be attributed to the regular colchicine treatment, which seems to have a cardioprotective role against vascular damage.

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.

Evaluation of Bone Mineral Density in Prepubertal Children with Familial Mediterranean Fever

Objective: Familial Mediterranean Fever (FMF) is a hereditary autosomal recessive chronic periodic inflammatory disease, characterized by recurrent fever polyserositis and skin manifestations. The aim of this study was to investigate the bone mineral density (BMD) in prepubertal children with FMF and to determine the relationship between bone density and demographic, laboratory characteristics of the disease. Material and Method: Thirty two previously diagnosed, attack-free, prepubertal FMF patients who were receiving regular colchicine treatment were included in the study. Demographic and clinical data of patients, acute phase reactants, biochemical parameters of bone turnover, bone age, and L1-L4 vertebral mineral density were evaluated. The results of the patients were compared with values determined for healthy Turkish children. Results: All of the patients had z-scores which were greater than -2. Acute phase values and bone metabolism markers were within normal limits. No correlation was found between the aBMD Z-score and demographic data, acute phase reactants and bone metabolism markers. There was a negative correlation between delay in diagnosis and aBMD Z- score. Conclusion: Although aBMD Z-scores were normal in children with FMF the aBMD Z score was found to be lower in children who had had a delay in treatment. Early initiated colchicine therapy is important for optimal bone health in these patients.

The role of colchicine treatment on reproductive outcome in women with Familial Mediterranean Fever

Öz&#x0D; Amaç: Bu çalışma, Ailevi Akdeniz Ateşi (AAA) tanısı alan ve kolşisin tedavisi verilen kadınların üreme sonuçlarını karşılaştırmak amacıyla planlandı.&#x0D; Gereç ve Yöntem: AAA tanılı 40 infertil kadın kolşisin tedavisi alıp almadığına bakılmaksızın iki gruba ayrıldı. 29 AAA hastası düzenli kolşisin tedavisi alırken, 11 hasta kolşisin tedavisi almıyordu. Hastalara tüp bebek kliniğimize başvurmadan önce AAA tanısı kondu. Tüm hastalar, hormonal profili, semen analizi ve histerosalpingografi (HSG) dahil olmak üzere baseline kısırlık incelemesine tabi tutuldu. Katılımcılara standart antagonist protokole göre ovulasyon stimülasyonu başlandı. Çalışmamızın birincil sonuç ölçütleri, klinik gebelik yüzdesi, abortus oranları, devam eden gebelik, canlı doğum ve term doğum oranları olarak belirlendi.&#x0D; Bulgular: HSG'de üç tür problem tespit ettik; (i) peritubal adezyon (ii) periovaryan adezyon ve (iii) hidrosalpinks. HSG'deki anormal bulgular nedeniyle 11 hastaya laparoskopi yapıldı. Kolşisin grubunda 8 olguda adezyon, kolşisin verilmeyen hastalarda ise 3 olguda adezyon tespit edildi. Kolşisin grubunda 8 vakada hidrosalpinks tespit edilirken, kolşisin almayanlarda sadece 1 vakada tespit edildi. Douglas poşundaki asit her iki grupta da ultrasonografi veya laparoskopi ile tespit edildi. Kolşisin almayan hastalarda, kolşisin alan hastalara göre klinik gebelik anlamlı derecede yüksek bulundu. Düşük oranları açısından iki grup arasında anlamlı fark yoktu. Kolşisin grubunda erken doğum oranları anlamlı olarak düşük bulunurken, zamanında doğum oranları kolşisin grubunda kontrol grubuna göre anlamlı olarak yüksek bulundu.&#x0D; Sonuç: Term gebeliklerin sayısı üzerindeki olumlu etkisi dışında, kolşisin tedavisinin üreme sonuçları üzerinde herhangi bir olumsuz etkisi tespit edemedik.&#x0D; &#x0D; Abstract&#x0D; Aim: This study was planned to compare the reproductive outcome of women diagnosed with Familial Mediterranean Fever (FMF) who were given colchicine treatment and those who were not. &#x0D; Material and Method: Forty infertile women with FMF were divided into two groups whether they received colchicine treatment or not. While 29 FMF patients received regular colchicine treatment 11 patients did not receive colchicine treatment. The patients were diagnosed with FMF before applying to our IVF clinic. All patients were subjected to full infertility work-up, including hormonal profile, semen analysis and hysterosalpingography (HSG). All women with FMF were treated according to a standard antagonist protocol. The primary outcome measures were the percantage of clinical pregnancy (CPR), miscarraige rates, ongoing pregnancy, live birth and term birth rates. &#x0D; Results: We detected three types of problems in HSG; (i) peritubal adhesion (ii) periovarian adhesion and (iii) hydrosalpinx. Eleven patients underwent laparoscopy due to abnormal findings in HSG. Adhesion was detected in 8 cases in the colchicine group, while adhesion was detected in 3 cases in the patients who were not given colchicine. Hydrosalpinx was detected in 8 cases in the colchicine group, while it was detected in only one case in those who did not take colchicine. Ascites in the Douglas pouch was detected ultrasonographically or by laparoscopy in both groups. The CPR was found to be significantly higher in patients who did not receive colchicine compared to patients who received colchicine. There was no significant difference between two groups in terms of miscarraige rates. While preterm birth rates were found to be significantly lower in the colchicine group term birth rates were significantly higher in colchicine group compared to control group. &#x0D; Conclusion: Except for the positive effect on the number of term pregnancies we could not detect any negative effect of the colchicine treatment on the reproductive outcome.

Is colchicine more effective to prevent periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis episodes in Mediterranean fever gene variants?

Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is the most frequent repetitive fever syndrome in childhood. It is characterized by fever episodes lasting for approximately 3-6 days, once every 3-8 weeks. Clinical and laboratory data for PFAPA syndrome patients between January 2010 and December 2014 followed up at a tertiary pediatric care hospital were reviewed. Four hundred children (256 male, 144 female; mean age at diagnosis, 4.2 ± 2.2 years), were enrolled in the study. During the episodes, mean leukocyte number was high (12 725/mm3 ) with predominant neutrophils. The mean number of monocytes was 1256/mm3 , and 90.2% had monocytosis. Serum amyloid A and C-reactive protein were high in 84.6% and in 77.8% of the patients, respectively. Mediterranean fever (MEFV) gene heterozygous mutation was identified in 57 of the 231 patients (24.7%) in whom genetic analysis had been performed. The most frequent mutation was heterozygous M694V (10%, n = 23). Extension of between-episode interval following prophylaxis was noted in 85% of those on regular colchicine treatment (n = 303). In the colchicine group, between-episode interval was prolonged from 18.8 ± 7.9 days (before colchicine treatment) to 49.5 ± 17.6 days on prophylactic colchicine therapy; also, prophylactic treatment was more effective in reducing episode frequency in patients with MEFV gene variant (n = 54, 96%) than in those without (n = 122, 80%; P = 0.003). This study has involved the largest number of PFAPA syndrome patients in the literature. It is particularly important to assess and to demonstrate the high rate of response to colchicine prophylaxis in PFAPA syndrome patients, especially those with MEFV variant. On blood screening, neutrophilia associated with monocytosis and low procalcitonin could contribute to diagnosis.

Efficacy of interleukin-1 targeting treatments in patients with familial mediterranean Fever.

Herein, we reported our experience in colchicine-resistant familial Mediterranean fever (FMF) patients who are treated with anti-interleukin-1 (IL-1) drugs. A retrospective review of medical records of anti-IL-1 recipients was performed. The main clinical characteristics of these patients and the evolution after anti-IL-1 were recorded. There were 20 patients (11 male [M] and 9 female [F]). Despite regular colchicine treatment, median number of attacks per month and per year was 1 (1-4) and 12 (4-50), respectively. Twelve patients were receiving anakinra, and eight patients were treated with canakinumab. The number of monthly and yearly attacks after IL-1 treatment was significantly decreased after the biologic agent (p < 0.05). One patient did not respond to the treatment, and one patient developed serious infection during anti-IL-1. We also observed a significant decrease in proteinuria in the amyloidosis complicated FMF patients. Anti-IL-1 targeting drugs seem safe and effective therapies in colchicine-resistant FMF.

THU0461 Evaluation of Various Endothelial Biomarkers and T Helper-17 Cytokines in Patients with Familial Mediterranean Fever

BackgroundFamilial Mediterranean fever (FMF) is a hereditary autoinflammatory disease that affects the populations with certain ethnic backgrounds. It is characterized by self-limiting febrile attacks of polyserositis. In recent years, some...

Evaluation of circulating endothelial biomarkers in familial Mediterranean fever

The aim of this was to evaluate some of the vascular biomarkers and cytokines related with atherosclerosis in regularly treated and attack-free familial Mediterranean fever (FMF) patients. Forty (21 males [M] and 19 females [F], 31 [15-58] years) FMF patients and eighteen healthy controls (11 M and 7 F, 35.5 [19-46] years) with no known cardiovascular (CV) risk factors were included. All patients were receiving regular colchicine treatment, and examinations were performed during attack-free periods. Serum samples were used for the determination of high-sensitive C-reactive protein (hs-CRP), tissue factor (TF), tissue plasminogen activator (t-PA), osteoprotegerin (OPG), interleukin-6 (IL-6), IL-17, and IL-23. Plasma samples were used for the determination of asymmetric dimethylarginine (ADMA) and thrombomodulin (TM). Age, sex distribution, waist circumference, body mass index, smoking status, and serum lipids were similar between the patients and controls (P > 0.05). The concentrations of (hs-CRP) and IL-17 were significantly higher in FMF patients compared with controls (P < 0.05). On the other hand, IL-6 and IL-23 levels were not different between the groups (P > 0.05). ADMA, OPG, and TM concentrations were significantly lower in the patients' group compared to those of controls (P < 0.05). However, vWF, TF, and t-PA levels were similar between the groups (P > 0.05). FMF patients receiving regular colchicine therapy during inactive disease state had significantly lower levels of vascular injury parameters.

The Effect of Regular Colchicine Treatment on Biomarkers Related with Vascular Injury in Newly Diagnosed Patients with Familial Mediterranean Fever

We aimed to evaluate some of the vascular biomarkers in newly diagnosed, colchicine naive familial Mediterranean fever (FMF) patients. Our primary aim was to investigate the effect of regular colchicine treatment on these variables. Twenty-four (12 males [M] and 12 females [F], 33.3 ± 13.4years) newly diagnosed FMF patients were included in the study. These patients were started on colchicine treatment following the initial assessment and were studied again no earlier than 2months. Five patients were lost to follow-up, and assessment of the on-treatment patients was performed on the remaining 19 patients (8 M and 11 F, 33.6 ± 11.8years). There were 19 healthy subjects (11 M and 8 F, 32.2 ± 7.2years) who served as a control group. Cellular adhesion molecules (CAMs; soluble intercellular adhesion molecule-1 [sICAM-1] and soluble CD146 [sCD146]), plasminogen activator inhibitor-1 (PAI-1), fetuin-A and hs-CRP were studied. Examinations were performed on attack-free periods. The levels of hs-CRP, fetuin-A, sICAM-1, and PAI-1 were significantly higher in newly diagnosed patients compared to those of controls (P < 0.05). All studied parameters were significantly downregulated after regular colchicine therapy (P < 0.05). Comparison of on-treatment data with controls showed that the levels of the vascular biomarkers, except sCD146, were similar between the groups (P > 0.05). On-treatment sCD146 was found significantly lower than the controls (P < 0.05). In regression analysis, none of the independent variables in the model significantly predicted the vascular biomarkers (P > 0.05). Administration of therapeutic doses of colchicine markedly reduces vascular injury parameters and normalizes the values in FMF.

Increased levels of circulating Annexin A5 in Familial Mediterranean fever

BackgroundFamilial Mediterranean fever is a genetic autoinflammatory disease most commonly affecting the ethnic groups originating from around the Mediterranean Sea. Apoptosis plays an important role in down-regulation of the inflammatory response by reducing the lifespan of activated immunocompetent cells. Thus, increased apoptosis may be associated with pathogenesis of familial Mediterranean fever.MethodsIn the present study we determined the serum levels of apoptotic marker, Annexin A5, in familial Mediterranean fever patients, within an attack and attack-free, in comparison to healthy subjects and assessed the influence of colchicine treatment on this parameter. In addition, in all study subjects serum levels of C-reactive protein and interleukine-1β, and the total leukocyte count were also determined.ResultsOur results demonstrated that pathogenesis of familial Mediterranean fever is characterized by the increased levels of circulating Annexin A5, which is higher in patients within the attack and which associate with the increased levels of C-reactive protein and interleukine-1β and total leukocyte count.ConclusionsThe results obtained indicate elevated rates of apoptosis of subpopulations of leukocytes involved in autoinflammation and recurrent episodes of fever in familial Mediterranean fever. It was also revealed that regular colchicine treatment sufficiently decreases the rate of apoptosis in familial Mediterranean fever patients by affecting the intensity of autoinflammatory reactions.

MEFV gene compound heterozygous mutations in familial Mediterranean fever phenotype: a retrospective clinical and molecular study

Familial Mediterranean fever (FMF) is an autosomal-recessive inherited inflammatory disease caused by mutations in the MEFV gene that encodes pyrin/marenostrin. It is characterized by recurrent short episodes of fever, abdominal pain and serositis affecting mainly Mediterranean and Middle Eastern populations. We determined the frequency of the compound heterozygous mutations which has been rarely reported. The present study not only investigated clinical features of child-onset FMF patients with compound heterozygous mutations but also determined whether there is a phenotype-genotype correlation in the same patient population. The medical records of 66 heterozygous patients with FMF were retrospectively reviewed and assessed. Patients were investigated regarding the mutation type, clinical characteristics at the time of inflammatory attacks such as fever, abdominal pain, arthritis, chest pain, erysipelas-like erythema and oedema, epidemiological data, consanguinity, severity score and family history of FMF and amyloidosis. The most frequent mutation was M694V, identified in 32% of the alleles examined, followed by E148Q in 20.6%, V726A in 17% and M680I in 14.5%, respectively. Consequently, we determined that P369S (n = 10; 8%) was the most frequent rare mutation in Turkish FMF patients. Frequency of the other rare mutations were R761H (3%), F479L (3%), A744S (1.5%) and K695R (0.7%). Fever was seen in 96.5%, abdominal pain in 98.5%, arthralgia in 85%, chest pain in 45.5% and erysipelas-like lesions in 23%. None of these patients had amyloidosis, but 16 had a family history of chronic renal failure, 44% had vomiting and 35% had diarrhoea during the attack. Although regular colchicine treatment was effective in 83% of the patients, the percentage of patients that did not start colchicine therapy was 18%. In addition, the patients were divided into four groups according to the presence of the mutation types and we compared genotype-phenotype correlations. We suggest that regular colchicine therapy may be administered to symptomatic patients with MEVF gene compound heterozygous mutations, regardless of the mutation type.

Selective Serotonin Reuptake Inhibitors Reduce the Attack Frequency in Familial Mediterranean Fever

Familial Mediterranean Fever (FMF) is characterized by recurrent acute attacks of fever and serositis, and colchicine is the primary treatment. The pathogenesis of the disease has not been fully understood. Resistance to colchicine remains to be a problem in up to 30% of the patients and yet there seems to be no alternative treatment. In this study our objective was to investigate whether a selective serotonin re-uptake inhibitor (SSRI) could affect the attack frequency and acute phase response in FMF patients who were unresponsive to colchicine. We retrospectively evaluated the hospital files of 11 colchicine-unresponsive FMF patients who had been treated with SSRIs. According to the records and re-evaluation of the patients, the total number of the FMF attacks was calculated before and after the SSRI, adjunct to colchicine. The laboratory values including erythrocyte sedimentation rate, C-reactive protein, fibrinogen and white blood cell counts were also noted before and after the SSRI treatment from their hospital files. The mean attack frequency before adding SSRI to colchicine was 8.09 +/- 3.53 per 6 months, and at the end of this period there was a great decline in the number of mean attack frequency (0.36 +/- 0.50 attacks per 6 months) (p < 0.001). Acute phase reactants were significantly decreased after SSRI treatment (p < 0.001). All of the colchicine-unresponsive patients had depression and 3 of those patients also had fibromyalgia. SSRIs appear to be useful adjuncts in the management of FMF patients who continue to have attacks despite regular colchicine treatment.

Rhabdomyolysis in a Patient Treated with Colchicine and Atorvastatin

To report a case of severe rhabdomyolysis that developed after administration of atorvastatin to a patient receiving regular colchicine treatment. A 45-year-old man with nephrotic syndrome and amyloidosis presented with dyspnea, altered mentation, and severe fatigue. He had been taking colchicine 1.5 mg/day for amyloidosis for 3 years without adverse effects. Atorvastatin 10 mg/day was prescribed for hypercholesterolemia one month prior to admission. After 2 weeks of atorvastatin treatment, he began to experience myalgia and reduced muscle strength. The creatinine and creatine kinase concentrations on admission were 8.1 mg/dL and 9035 U/L, respectively. The patient was diagnosed with rhabdomyolysis with the findings of myoglobinuric, oliguric acute renal failure, and more than 50-fold elevated creatine kinase concentration. His muscle strength improved after withdrawal of atorvastatin and colchicine. However, he died because of nosocomial pneumonia that developed during his hospital stay. The Naranjo probability scale indicated that atorvastatin and colchicine were probable causes of rhabdomyolysis. Atorvastatin and colchicine have well-known myotoxic adverse effects. Despite atorvastatin's proven safety, its use with certain drugs, such as colchicine, makes it a potential myotoxic drug. This might be because concomitant administration of P-glycoprotein substrates, such as statins, and colchicine, which is a P-glycoprotein inhibitor, modifies pharmacokinetics by increasing bioavailability and organ uptake of the substrates, leading to more adverse reactions and toxicities. We recommend checking the creatine kinase level one week after prescribing 2 or more potentially myotoxic drugs concomitantly, after dose increase of a myotoxic drug, or after prescribing a new drug to a patient already using other myotoxic agents.

Hypercoagulability: interaction between inflammation and coagulation in familial Mediterranean fever

Familial Mediterranean fever (FMF) patients in clinical remission are reported to have increased baseline inflammation. Normal function of the natural anticoagulant pathways is particularly needed in diminishing inflammatory responses. In the presence of subclinical inflammation, natural anticoagulant response may be exaggerated. We aimed to observe the anticoagulant-procoagulant status in attack-free FMF patients. Twenty-seven FMF patients diagnosed in accordance with Tel-Hashomer criteria, and 26 healthy controls were included. All patients were attack-free under regular colchicine treatment. Amyloidosis, autoimmunity, accompanying liver and renal disease, and vasculitis were excluded. Predisposing factors for thrombosis were not present. Acute phase reactants (APRs), anticardiolipin antibody positivity, prothrombin time (PT), activated prothrombin time, thrombin time (TT) and d-dimer, protein C activity, activated protein C resistance, free protein S, antithrombin, lupus anticoagulant, human prothrombin fragment F 1 + 2, and human thrombin/antithrombin III complex were analyzed for all subjects. APRs were comparable with controls. Autoimmune markers were negative in all. Anti-streptolysin titers were significantly different than the control group. PT, TT, protein C activity, and F 1 + 2 levels were significantly different from those of healthy controls. Shortened PT and TT, decreased protein C activity vs increased levels of F 1 + 2 suggested a hypercoagulable state in our patients. The hypercoagulable state detected in FMF patients suggests that screening with abnormal coagulation tests may be beneficial for tracing the future consequences of subclinical inflammation in these patients. Studies covering larger groups of patients are needed to verify the currently observed hypercoagulable status in FMF.

Classical pathway complement activity in Familial Mediterranean fever

Objectives: The present study emphasizes the important role of the immune reactions in the pathogenesis of Familial Mediterranean fever. In the present study, the total hemolytic activity of the complement and the activities of individual complement components, C1, C2, C3, and C4, were determined in the blood serum of 32 patients with FMF and 28 healthy subjects. Design and methods: Hemolytic assay was applied, measuring THAC and individual complement components' activities. The patients were divided into 3 groups upon the regularity of colchicine therapy: patients receiving regular, irregular and not receiving colchicine treatment for at least 1 year. Results: No significant changes in the hemolytic activities of the C1, C2, C3, and C4 complement components were found between the healthy subjects and those FMF patients, who were receiving regular colchicine treatment. Conclusions: Our data obtained have raised a number of important questions relevant to FMF pathogenesis and once again confirms the efficiency of regular colchicine treatment.

The efficacy of interferon alpha on colchicine-resistant familial Mediterranean fever attacks: a pilot study

About a quarter of familial Mediterranean fever (FMF) patients have recurrent painful attacks of polyserositis despite regular colchicine treatment. There is no known alternative drug for colchicine-resistant cases. We had previously observed a patient with FMF whose painful attacks disappeared during the 6 month period of interferon alpha (IFN) treatment for his chronic hepatitis B. The objective of the present study was to investigate the possible beneficial effect of IFN on these episodes. Twenty-one consecutive attacks in seven adult patients with FMF were treated at early onset with IFN, the dosage being 3-10 million I U s.c. Eighteen of the 21 attacks could be halted in a mean time of 3.05 h, while the intensity of abdominal pain remained very low. Observed side-effects were generally mild and acceptable. IFN may be a useful adjunct for the treatment of colchicine-resistant attacks in FMF patients.