Hakan Babaoglu

Efficacy and safety of interleukin-1 inhibitors in familial mediterranean fever patients complicated with amyloidosis

Abstract Background: Colchicine is the mainstay of the treatment of familial Mediterranean fever (FMF). However, 10% of FMF patients do not respond well to colchicine. Efficacy of interleukin (IL)-1 inhibitors in reducing attacks have been demonstrated in colchicine-resistant FMF (crFMF) patients recently. Colchicine is still the only approved drug for the prevention of amyloidosis in FMF and utility of IL-1 inhibitors in crFMF cases who already has amyloidosis remain to be elucidated. Herein, we evaluated efficacy and safety of IL-1 inhibitors in patients with crFMF-associated AA amyloidosis in a relatively large single center study. Methods: Medical records of FMF patients complicated with AA amyloidosis in our dedicated FMF center were retrospectively reviewed and those patients who ever treated with IL-1 inhibitors were enrolled into the study. Patient global, physician global assessments (on 0–10u2009cm visual analog scale), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum creatinine and 24-h urinary protein excretion values for each visit were recruited from computer-based hospital records. Treatment response of patients were assessed with clinical symptoms, serum albumin, CRP and ESR values. Renal outcome parameters were analyzed on those not receiving renal replacement therapy. Results: Seventeen patients were identified with crFMF-amyloidosis that ever treated with IL-1 inhibitors. Background colchicine therapy was continued in all patients in maximal-tolerated dose along with IL-1 inhibitors. All patients benefit from IL-1 antagonists assessed by patient and physician global assessments. Inflammatory markers, CRP and ESR, were significantly reduced in all and normalized in 12 out of 17 patients. More importantly, the amount of proteinuria was remarkably improved following IL-1 inhibitor therapy (1606u2009mg/day to 519u2009mg/day, pu2009=u2009.008). Both anakinra and canakinumab were well-tolerated without severe side effects. All patients were initially treated with anakinra but switched to canakinumab in seven patients (one leukopenia, four injection site reaction, two inefficacy). Conclusion: We evaluated the clinical and laboratory responses to IL-1 inhibitors in crFMF-associated amyloidosis patients. We found significant decreases in CRP, ESR and proteinuria after IL-1 inhibitor therapy. This study confirmed that IL-1 inhibitors are effective for controlling attacks and inflammatory activity in FMF patients complicated with AA amyloidosis. Moreover, they reduce or stabilize amount of proteinuria and preserve renal function in short-term follow-up. Prolonged prospective clinical trials are warranted to assess their long-term efficacy in this particular patient group.

Associations between Depressive Disorders and Inflammatory Rheumatic Diseases

Depressive disorders, are not only common but also among the leading causes of disability worldwide. They are associated with increased incidences of various other diseases. It has been shown that in patients with autoimmune diseases, when depression coexists, the quality of life is worse and medical treatment and management is compromised. Depression-like symptoms, such as fatigue and disinterest are also common in inflammatory rheumatic diseases and often associated with poor quality of life. Medical therapy targeting inflammation results in alleviation of these symptoms in many patients. Interestingly, there is cumulating evidence suggesting potential roles of inflammatory cytokines in the pathogenesis of major depression. Effects of some of the biological agents used in rheumatic diseases have been studied on depressive disorders. Results have been controversial and further studies are needed in this area. These findings suggest associations between depression and inflammatory rheumatic diseases and raise the possibility that treatment of one of them might influence the outcome of the other. We have reviewed the current literature on associations between depression and inflammatory rheumatologic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Sjögrens syndrome and ankylosing spondylitis.

On demand use of anakinra for attacks of familial Mediterranean fever (FMF)

To evaluate the efficacy of on-demand use of anakinra in patients with crFMF. The Gazi FMF cohort was established in the year 2010, and from that date, 689 patients with FMF diagnosed according to the Tel Hashomer criteria were registered. Attack type, duration, severity, and their impact on life were collected either by disease diaries or a mobile phone application (FMF AIDD, AppStore, and Playstore). A retrospective cohort analysis was made from records of patients who have ever been treated with IL-1 inhibitors. A total of 78 patients were treated with IL-1 inhibitors in our cohort. Among these, 15 patients were identified who received on-demand anakinra. Rationale for on-demand use was prominent prodrome or trigger for attacks and patient’s personal claim. Six patients were switched from regular use and nine were directly started as on-demand use. All were using background colchicine in maximum tolerated doses. None of the patients had evidence of persistently elevated acute phase reactants or proteinuria. The median duration of on-demand anakinra use was 6 (3–36)xa0months. Pre- and post- on-demand anakinra periods were compared. Patient reported attack severity (pu2009=u20090.002), duration (pu2009=u20090.001), frequency (pu2009=u20090.001), absenteeism (pu2009=u20090.002), and presenteeism (pu2009=u20090.002) were significantly improved. On-demand anakinra prevented progression of prodromes to full-blown attacks which was demonstrated by decrease in the rate of attack/prodrome ratio (pu2009=u20090.02). On-demand anakinra can be continued in ten subjects on long-term. On-demand anakinra significantly improved FMF attacks in certain patients which suggest this approach would be of benefit in daily practice in selected patients.

Should our approach to diuretic using in patients with gout change

We read with interest the recent article by Ranieri et al. [1]. The intention of the authors was to investigate the impact of diuretic therapy on the response of urate-lowering drugs (ULDs) in patients with gout. According to the results of this study, diuretic therapy did not impair response to ULDs. Also, there was no significant effect of diuretic use on the achievement of serum urate (SU) targets or on the maximum doses of ULDs. However, it is known that the European League Against Rheumatism (EULAR) has reported its concern in regard to the use of diuretics in patients with gout and recommends substitution of diuretic to losartan or calcium channel blockers if gout is diagnosed in a hypertensive patient receiving loop or thiazide diuretics [2]. For this reason, we believe that the results of this study, which reported the incompatibility with the recommendations of known and accepted organizations, should be interpreted carefully as it may bring a question mark to daily clinical practice. First, the retrospective design of the study led to the heterogeneity of the patient population. Given the baseline characteristics of enrolled patients, 137 (65.9%) patients in the allopurinol group and 30 (85.7%) in the febuxostat group had hypertension. In addition, 107 (51.4%) patients in the allopurinol group and 20 (57.1%) patients in the febuxostat group had dyslipidemia. But in this study, we did not find any information about the drugs used for hypertension and dyslipidemia which may have an effect on urate metabolism. A large epidemiological study reported that calcium channel blockers and losartan are associated with a lower risk of incident gout among patients with hypertension [3]. It is well known that fenofibrate and statins have uricosuric properties [4, 5]. Second, in the study, alcohol use and dietary habits of patients may directly affect the SU levels. But there is no detailed information on alcohol use and dietary habits of patients. All of these factors may have affected the results of the study. Lastly, given diuretic indications, 63% of patients using diuretics had pure hypertension without heart failure or chronic kidney disease. In these patients, although there are alternative anti-hypertensive drugs, the reason for the continuation of diuretics after diagnosis of gout is a matter to be discussed. In conclusion, the results of this study, which can change our clinical practice, consisting of a retrospective and heterogeneous population, should be interpreted with caution. We believe that, as the authors emphasize, there is a need for prospective well-designed studies about the effects of diuretics on the necessary doses of ULDs to achieve the targeted SU level.

Inconsistency between supplement and article

In their recent article in the Annals of the Rheumatic Diseases , van der Heijde D et al 1 evaluated the effect of certolizumab pegol (CZP) on radiographic progression in patients with ankylosing spondylitis and non-radiographic axial spondyloarthritis (nr-axSpA). They suggested that CZP-treated patients …

SAT0611 Canakinumab use in adult familial mediterranean fever patients: a large single centre experience

Background IL-1 blocking agents have been shown to be effective in the prevention of attacks in colchicine resistant FMF (crFMF) patients. Canakinumab is FDA approved long acting recombinant IL-1 receptor antagonist for use in crFMF patients which is available for off label use in Turkey. Herein, we aimed to share our real life single centre experience for use of canakinumab in adult crFMF patients. Methods Data was derived from Gazi FMF cohort which was established in year 2010. From that date patients with FMF who were diagnosed according to the Tel Hashomer criteria were registered. Co-morbidities, detailed attack characteristics, type, duration, severity, treatments, laboratory parameters and impact of FMF on their life in terms of quality of life and work productivity were recorded either by FMF diary or a mobile phone application (FMF AIDD free to download from AppStore and android market). A retrospective cohort analysis was made from records of patients who were treated with canakinumab. Results Eighteen adult crFMF patients (%61 female) treated with canakinumab were enrolled in this study. The median age was 3124–58 years and the median disease duration was 2816–40 years. All patients harbour homozygous or compound heretozygos exon 10 MEFV mutations. Treatment reasons for canakinumab were colchicine resistance (n=14) and amyloidosis (n=4). In three patients canakinumab was initiated directly, while in 15 it was switched from anakinra (seven was allergic to anakinra, one patient had significant leukopenia, in six fail to control attacks). The median duration of canakinumab use was 8 (min 1- max 22) months. In two patients canakinumab was used as 300u2009mg/monthly, and in remaining as 150u2009mg/monthly. Pre- and post-canakinumab periods of patients were compared (Table). Patient reported attack severity (p≤0.01), duration (p≤0.01), frequency (p≤0.01), C-reactive protein (CRP) (p≤0.01) and erythrocyte sedimentation rates (p≤0.01) were significantly improved while serum creatinine and alanine aminotransferase (ALT) levels remained same (p=0.2, p=0.35, respectively). Canakinumab achieved complete disease remission in 5 patients. Side effects requiring discontinuation of canakinumab were observed in none of patients. Table. Comparison of attack characteristics of 18 Adult crFMF patients before and after canakinumab Colchisine Colchicine+canakinumab P Attack severity, VAS 8,5 (5–10) 3,5 (0–10) <0,01 Attack duration, hours 108 (48–144) 24 (0–96) <0,01 Attack frequency* 6 (1–10) 1 (0–3) <0,01 CRP, mg/L 35,8 (3,8–85,0) 4,2 (2,45–55) <0,01 ESR, mm/h 38 (11–67) 12 (3–44) <0,01 Serum creatinine 0,66 (0,40–3,00) 0,70 (0,43–3,00) 0,20 ALT 20 (10–55) 19 (9–70) 0,35 Treatment duration, months 204 (48–456) 8 (1–22) *Attack frequencies adjusted for 3u2009months intervals. VAS: visual analogue scale, CRP: C-reactive protein, ALT: alanine aminotranspherase, ESR: erythrocyte sedimentation rate Conclusions Canakinumab is effective in the prevention of attacks with a favourable safety profile. Disclosure of Interest None declared

AB0472 Impact of disease on family and social life in women with systemic lupus erythematosus (SLE)

Background Systemic lupus erythematosus (SLE) is a chronic connective tissue disease with involvement of various organ systems and characteristically has a higher incidence in women than men1. The disease, as well as its treatment, could have significant effects on the quality of life of lupus patients. Objectives Here, we aimed to investigate the impact of SLE on quality of the social and family life of women. Methods One hundred and twenty women diagnosed with SLE were included in the study. A questionnaire including questions about family and social relations were applied and demographic information, educational status, marital status, organ involvement and treatment data were obtained. The results of this study are preliminary and the study is still ongoing. Results One hundred and twenty patients were studied. The average age was 37 (± 10). 77 patients were married, 29 patients were single, 12 patients were divorced and 2 patients were widows. 29% of the patients were employed. 10,8% of the patients declared having difficulty in accepting their illnesses. 94,8% of the married patients had nuclear families. Relationship with partners and family members detoriated in 15,5% of the married patients after the diagnosis of SLE. 10,7% of single patients ended their serious relationships and 28,6% developed negative thoughts about marriage after the diagnosis of SLE. 17,6% of the married patients were exposed to verbal or physical violence by their partners. 33% of the patients declared having worse social life compared to prior to diagnosis and 20,7% declared having poor relations with their friends due to their disease. 34.5% of the patients stated that they received psychological counseling after their diagnosis. No significant relationship was found between family problems, social activities, age and educational level. Conclusions Systemic lupus erythematosus is a connective tissue disease affecting various organ systems and leading to various comorbidities. Our results suggest that family and social relations detoriate in lupus patients due to their illness independent of their age and educational level. Over one third of the patients received psychological counseling after diagnosis. Moreover, results of this study suggest that having a diagnosis of lupus has substantial impact on the marital considerations. References Hochberg, Marc C. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis & Rheumatology 40.9 (1997): 1725–1725. Disclosure of Interest None declared

FRI0320 Predictive value of platelet to lymphocyte ratio in renal involvement in patients with granulomatosis with polyangiitis

Background Granulomatosis with polyangiitis (GPA) is a granulomatous necrotizing vasculitis with high morbidity and mortality. Anti-neutrophil cytoplasmic antibody (ANCA) is a rvaluable diagnostic marker, however its titer lacks predictive value for the severity of organ involvement. Platelet to lymphocyte ratio (PLR) and mean platelet volume has been regarded as a potential marker in assessing systemic inflammation. Objectives We aimed to investigate PLR and MPV as inflammatory marker in patients with GPA. Methods GPA patients and age-sex matched healthy controls were included. Demographic, clinical and laboratory information were extracted from medical records. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood cell (WBC), platelets (PLT), lymphocyte and neutrophils counts and glomerular filtration rate (GFR) were recorded. PLR was calculated. Disease activity was assessed with Birmingham Vasculitis Activity Score for WG vasculitis (BVAS/WG). Results 56 patients with GPA and 53 healty controls were included. Clinical characteristics and laboratory findings of the study population are shown in Table 1. ESR, CRP, MPV and PLR were significantly higher in patients with GPA than controls. PLR positively correlated with ESR and CRP (r:0.389, p:0.005 and r:0.512 p<0.001, respectively). In contrast, MPV negatively correlated with ESR and CRP (r:-0.308, p:0.028 and r:-0.337 p:0.014, respectively). There were no significant correlation between PLR, MPV and BVAS/WG. Patients with renal involvement had statistically significantly higher PLR than patients without renal involvement (303.01±287.33 vs177.98 + 75.43, p: 0.020 respectively). Moreover PLR negatively correlated with glomerlar filtration rate (r:-0.266 and p:0.009). Receiver operating characteristic curve of PLR, ESR and CRP for differentiating renal involvement is presented in Figure 1. Area Under Curves (AUCs) for PLR, CRP and ESR were 0.703 (95% confidence interval [CI], 0.558–0.849, p=0.016), 0.577 (95% CI: 0.416–0.738, p=0.362), 0.508 (95% CI: 0.337–0.678, p=0.929), respectively. The cutoff level of PLR was 204 (sensitive 65.6%, specifity 62.5%, positive predictive value 70%, negative predictive value 57.7%). Patients with alveolar hemorrhage tended to have higher PLR but this difference did not reach statistically significance (266.60 + 182.90 vs 240.61 + 252.43 p=0.382, respectively). Conclusions Results suggest that PLR exhibit favorable diagnostic performance in predicting renal involvement in patients with GPA. Disclosure of Interest None declared