[Show abstract][Hide abstract] ABSTRACT: This open-label pilot study aimed to investigate the efficacy of canakinumab in colchicine-resistant familial Mediterranean fever (FMF) patients.
Patients with one or more attacks in a month in the preceding 3 months despite colchicine were eligible to enter a 30-day run-in period. Patients who had an attack during the first run-in period advanced to a second 30-day period. At the first attack, patients started to receive three canakinumab 150 mg subcutaneous injections at 4-week intervals, and were then followed for an additional 2 months. Primary efficacy outcome measure was the proportion of patients with 50 % or more reduction in attack frequency. Secondary outcome measures included time to next attack following last canakinumab dose and changes in quality of life assessed by SF-36.
Thirteen patients were enrolled in the run-in period and 9 advanced to the treatment period. All 9 patients achieved a 50 % or more reduction in attack frequency, and only one patient had an attack during the treatment period. C-reactive protein and serum amyloid A protein levels remained low throughout the treatment period. Significant improvement was observed in both physical and mental component scores of the Short Form-36 at Day 8. Five patients had an attack during the 2-month follow-up, occurring median 71 (range, 31 to 78) days after the last dose. Adverse events were similar to those observed in the previous canakinumab trials.
Canakinumab was effective at controlling the attack recurrence in patients with FMF resistant to colchicine. Further investigations are warranted to explore canakinumab's potential in the treatment of patients with colchicine resistant FMF.
ClinicalTrials.gov NCT01088880 . Registered 16 March 2010.
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Fatigue is an important problem in inflammatory diseases and affects the quality of life (QoL). We aimed to evaluate the severity and impact of fatigue in Behçet's syndrome (BS) and to determine its association with type of organ involvement and gender.
One hundred and fifty-two BS, 51 rheumatoid arthritis (RA), 51 systemic lupus erythematosus (SLE), 51 ankylosing spondylitis (AS) patients and 65 healthy controls were evaluated by the fatigue severity scale, fatigue impact scale, fibromyalgia impact questionnaire (FIQ), RAPID3, SF-36 and Behçet's syndrome activity scale (the latter only in BS patients). We also analysed subgroups of BS patients with predominantly eye, vascular, joint and mucocutaneous involvement and did an additional gender analysis.
Fatigue severity and fatigue impact scores were similar among BS, RA, SLE and AS patients and significantly higher than that in healthy controls (F4df =8.51; p<0.001 and F4df = 8.67; p<0.001, respectively). The fatigue severity and fatigue impact scores were similarly high in BS subgroups with different types of organ involvement, and in both genders.
Fatigue is an important problem in BS, as it is in other inflammatory conditions. It is similarly severe in subgroups of patients with eye, vascular, joint and mucocutaneous involvement and in either gender. Fatigue is a candidate outcome measure for clinical trials, to assess the life impact of Behçet's syndrome.
Clinical and experimental rheumatology 10/2015; · 2.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives Behçet's syndrome (BS) is most active during young adulthood and may cause severe disability. We had previously observed a high frequency of work disability among our Behçet's patients in a cross-sectional study. This time we aimed to evaluate the sustainability of work among our patients who did have a job 5 years ago.
Methods We had surveyed work disability among 300 consecutive Behçet's syndrome patients who attended our clinic in 2009. We had observed that after excluding students, homemakers and retired patients, among the 149 work eligible patients 29 (21%) were unemployed and 120 were employed. We now evaluated those patients who did have a job 5 years ago regarding work loss and reasons for work loss, using a standard questionnaire. We also checked their hospital charts for new types of organ involvement that developed during these 5 years, and any new medications that were started.
Results Among the 120 patients who did have a job in 2009 (87 men, 33 women, mean age 36±8.6, disease duration 9.7±7.1 years, 48% with major organ involvement), we were able to contact 97 patients. Sixteen patients (16%) had lost their jobs during the previous 5 years. Nine of these (11%) were related with Behçet's syndrome and the rest were due to other causes (5 had retired, 1 had a baby, 1 was doing his military service). Among the 81 patients who were still working, 10 (10%) had to change their work place during the last 5 years and were unemployed for a mean of 6.7±5.3 months between these jobs.
Conclusions Work disability is an important problem among Behçet's syndrome patients. During a 5 year follow-up, 11% of patients lost their jobs due to their disease, and a further 11% had to interrupt work and change their work places. We were only able to evaluate work disability in this study, and work productivity is another important issue that needs to be studied among patients with Behçet's syndrome.
Disclosure of Interest None declared
Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):298.4-299. DOI:10.1136/annrheumdis-2015-eular.5822 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background BCG vaccination is thought to cause false positive PPD and concomitant medications to cause false negative PPD results when screening patients before starting TNF-alpha antagonists. Moreover it is assumed that INH is difficult to tolerate in this patient group. However there is a long time between BCG vaccination and TNF-alpha antagonist use in most of the rheumatology patients; there is no consistent data to show that medications cause negative PPD results; and INH is usually well tolerated by most of our patients.
Objectives To determine whether BCG vaccination causes false positive PPD, concomitant medications cause false negative PPD and whether INH is difficult to tolerate in these patients.
Methods We included adult patients who were prescribed a TNF-alpha antagonist for the first time between January 2010 and December 2012 in our clinic. Patients who had a history of active tuberculosis were excluded. BCG vaccination was determined by checking for BCG scars. We used logistic regression to analyse the determinants of a positive PPD (≥5 mm). The variables were having a BCG scar, each medication, age, gender, diagnosis and disease duration. We also evaluated the frequency of being able to complete 9 months of INH treatment and the reasons for discontinuation.
Results A TNF-alpha antagonist was started in 1229 patients (613 men, 616 women, mean age 39.53±13.82 years, disease duration 6.49±6.87 years). We excluded 136 patients who had previously used a TNF-alpha antagonist, 21 patients younger than age 18 and 41 patients who had previous tuberculosis treatment. Among the remaining 1031, an initial PPD test was available in 873, and QTF in 215 patients. At least one BCG scar was present in 757 patients. Multivariate regression analysis showed that BCG vaccination and male sex were associated with PPD positivity (OR=3.21, 95%CI 1.87-5.52, p<0.001; and OR=2.51, 95%CI 1.78-3.53, p<0.001 respectively), while azathioprine use was associated with a negative PPD (OR=0.50, 95%CI 0.27-0.93, p=0.029). 482/565 (85.30%) patients completed 9 months of treatment, 30 with interruptions and 34 with mild transaminase elevations not requiring interruption. 69 (12.21%) had to stop INH after 3.43±2.27 months. The reasons were hepatotoxicity in 31, non-willingness in 13, allergic dermal reactions in 6, nausea in 2, dizziness in 2, pregnancy in 1, shortness of breath in 1 and pancreatitis in 1 patient. Twelve patients stopped taking INH after their TNF-alpha therapy was stopped. Among the 31 who had to stop INH for transaminase elevation 7 were using concomitant methotrexate. None of the patients developed tuberculosis during our follow-up of up to 3 years.
Conclusions BCG vaccination may still be a cause of false positive PPD in candidates for treatment with TNF-alpha antagonists. Azathioprine seems to be associated with negative PPD. INH prophylaxis is generally well tolerated despite concomitant methotrexate.
Disclosure of Interest None declared
Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):702.1-702. DOI:10.1136/annrheumdis-2015-eular.6163 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background There is still controversy about the association of TNF-alpha antagonists with malignancies. Although recent meta-analyses suggest that the risk of malignancy with these agents is not increased, the suspicion still exists, at least as reflected by the current labeling information.
Objectives To survey the incidence of malignancy in patients treated with TNF-alpha antagonists for up to 13 years in a single center and to compare the results with the incidence of malignancy in the general population.
Methods The charts of the first consecutive 376 rheumatoid arthritis (RA) patients (307 women; 69 men; mean age 55.5±12.7 SD years) who were prescribed TNF-alpha antagonists between 2001 and 2009 were reviewed retrospectively. Information regarding the demographic and clinical features, duration of use each TNF-alpha antagonist, development time and type of malignancy and the outcomes of patients were recovered from patient charts. Patients were invited to the clinic if their current status was not known. Age and sex standardized cancer incidence rates in the general population used to calculate standardized cancer rates (SIRs) were obtained from the Turkish Ministry of Health, Public Health Institution, Department of Cancer.
Results The mean duration of follow-up was 67.6±17.7 SD months from the start of the first TNF-alpha antagonist to the end of 2013. During this time, 30 (7.9%) patients had died, 132 (35.1%) were still on TNF-alpha antagonists, 67 (17.8%) were using another biologic, 138 (36.7%) were no longer using any biologics and 10 (2.6%) were lost to follow-up. The main reasons of death were cardiovascular causes in 7 patients, sepsis in 5 and malignancies in 4. In 10 (2.6%) patients cause of death was unknown. A total of 8 patients had developed malignancies (2.12% [95% CI 0.66-3.58]). These were solid cancers in 6 (breast =1, lung =1, gastric =1, rectum =1, colon =1, unknown primary=1), hematologic cancers in 2 (acute leukemia=2). Since there were patients who were lost to follow-up and those who died of unknown causes, we calculated SIRs according to three different scenarios. If we assume that none of the patients who were lost to follow-up or whose cause of death was unknown, had a malignancy, the SIR would be 0.78 (95% CI 0.34-1.42). If we assume that all of the patients who were lost to follow-up (n=10) had a malignancy, but none of the patients whose cause of death was unknown had a malignancy, the SIR would be 1.7 (95% CI 1.04-2.0). Finally if we assume all patients who were lost to follow-up or whose reason of death was unknown (n=20) had a malignancy the SIR would be 2.7 (95% CI 1.8-3.8).
Conclusions Our data indicate that an increased incidence of cancer, as compared to the general population, cannot be ruled out among RA patients enrolled in a TNF – alpha antagonist registry. This uncertainty is compounded by the fact that the comparisons we make here are between the incidence in a cohort of practically cancer free patients at the time of cohort entry and a general population incidence in which no such restriction is present.
Disclosure of Interest None declared
Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):1040.2-1040. DOI:10.1136/annrheumdis-2015-eular.4337 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background Juvenile spondyloarthropathies (JSpA) are a group of chronic childhood rheumatic diseases which emerge especially before 16 and after 6 years-old. While enthesitis and oligoarthritis are the major signs of the early period, axial skeletal involvement and sacroiliitis are the late period signs. Although the diagnosis of the spondyloarthropathy is easy in adults, it is quite difficult in children.
Objectives To determine clinical and demographical features of the JSpA cases that is followed-up in our department, and to evaluate treatment modalities and long term complications of disease together with the side effects of the drugs.
Methods 107 children (21 female, 86 male) that admitted to our clinic with the diagnosis of JSpA between January 2005-December 2014 were involved in our study. Enthesitis related arthritis and Juvenile Ankylosing Spondylitis were included under the topic of JSpA. Clinical and laboratory variables were obtained from patient records.
Results While the mean age of the disease onset and diagnosis were 11,4±3 years (range 3 -17 years) and 12,4±2,8 years (range 5-18 years) respectively, the mean duration of follow-up period was 2,7±2,5 years (range 2 months-12 years). Lower extremity arthritis (n=83, 77,6%), hip pain (n=63, 58,9%) and inflammatory low back pain (n=47, 43,9%) were the major clinical findings. The most seen involvement of the lower extremity was ankle joint arthritis (n=60, 72,3%) followed by enthesitis (n=76, 71%) and tarsitis (n=30, 28%). Axial skeletal involvement was noted in 57% (n=61) of patients and mean inflammatory low back pain duration was 8,3±6,9 months (range 1-24 months). Magnetic resonance imaging could be studied in 77 patients (72%) that imaging results of 52 children (48,6%) were consistent with sacroiliitis. Lumbar movement limitation in Schober's test was seen in 42 cases (39.3%). Family history of spondylitis in 29 children (27.1%) and familial Mediterranean fever (FMF) in 4 cases. Furthermore, 5 patients diagnosed as FMF and treated with colchicine. Uveitis was seen in 11 children (10.3). Cardiological, pulmonary and renal investigations were normal of the whole study. HLA-B27 tissue antigen was positive in 73.8% (n=79) of the patients. First line therapies were methotrexate in 51 cases (47.5%) and sulphasalazine in 40 cases (37.4%). Anti-TNF alpha agents were used in 51 patients (47,7%) that were resistant to first line therapy. In the last medical visits we evaluated the patients in the terms of treatment modalities; 60.7% (n=65) of cases were noted as using drugs and in remission, 12.1% (n=13) gave up drugs and in remission, 16.8% (n=18) as minimally active and 6,5% (n=7) as active.
Conclusions Initial signs of JSpA are usually lower extremity arthritis and enthesitis in children that is quite different from adults. JSpA should be strongly suspected in the case of a boy that is older than 6 years-old with lower extremity arthritis and the family history of spondyloarthropathy. Afterwards, axial skeletal evaluation must be investigated immediately and in order to prevent this complication true and efficient therapy must be started.
Disclosure of Interest None declared
Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):390.2-390. DOI:10.1136/annrheumdis-2015-eular.6017 · 10.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background The use of TNF-alpha inhibitors is associated with an increased risk of tuberculosis (TB) and all guidelines recommend discontinuation of TNF-alpha inhibitors if active TB develops. However discontinuation of treatment can result in flare of the underlying disease and there is fairly limited data about the safety of re-administration of biologics.
Objectives To determine the safety of re-administration of biologic agents in patients who had developed active TB during anti TNF-alpha treatment.
Methods The charts of 21 patients (11 men, 10 women; mean age 38.4±13.2 SD years and mean disease duration 10.6±7.8 SD years at the time of TB development) who developed active TB (8 pulmonary, 13 extrapulmonary) during anti TNF-alpha treatment (15 with infliximab, 3 with adalimumab and 3 with etanercept) in our clinic between 2001 and 2013 were reviewed retrospectively. Patients were invited to the clinic if their current status was not known. The mean follow-up between re-administration of biologics and the end of our survey was 38.1±28.5 SD months.
Results Among the 21 patients who developed TB during anti TNF-alpha treatment, 1 patient with miliary TB died during the first month of anti-TB treatment. A biologic agent was restarted in 15 of the 20 remaining patients (75%). The first re-administrated biologic agent was etanercept in 6 patients (4 AS, 1 RA, 1 Behçet's syndrome), adalimumab in 1 AS patient, golimumab in 1 AS patient, rituximab in 5 patients (4 RA, 1 Takayasu), and interferon-alpha in 2 Behçet's patients. Biologic treatment was reinitiated while anti-TB treatment was ongoing in 3 patients (etanercept in 1 Behçet's patient at month 3, rituximab in 2 RA patients at month 4), and a median of 3.5 months (IQR: 0.6-22.2 months) after the completion of anti TB treatment in 12 patients. In 6 patients treatment was switched to another biologic (infliximab, adalimumab, golimumab, abatacept, rituximab and canakinumab in 1 patient each) due to lack of efficacy.
One of these 15 patients developed TB again and another patient died with gastric cancer. The patient who developed TB again was a Behçet's patient who had initially used infliximab. He had developed pulmonary TB on the 18th month of infliximab and infliximab was stopped. At the third month of anti TB treatment, etanercept was started due to severe sight-threatening uveitis and anti-TB treatment was completed to 6 months. Etanercept was continued for 15 months and then was replaced with canakinumab due to inadequate response. He developed tuberculous meningitis while receiving the 3rd dose of canakinumab in combination with methotrexate, cyclosporine and steroids. He received another 9 months of anti-TB treatment and is currently stable on IFN-alpha therapy for 16 months.
Conclusions Biologic agents, including TNF-alpha antagonists, can be reinitiated in patients who had previously developed TB under anti TNF treatment. Careful follow-up for TB reinfection is required.
Disclosure of Interest None declared
Annals of the Rheumatic Diseases 06/2015; 74(Suppl 2):472.1-472. DOI:10.1136/annrheumdis-2015-eular.2512 · 10.38 Impact Factor