Background:
Even though corticosteroids and cDMARDs are effective for inducing remission in patients with Adult-Onset Still Disease (AOSD), relapse is common. Hence, maintaining the clinical ...stability is challenging. Almost all of the patients face side effects because of high dose steroid treatment. Biological DMARDs have been reported to be effective in refractory patients.
Objectives:
We aimed to evaluate the patients’ outcomes who were diagnosed with AOSD and treated with at least one bDMARDs in our tertiary center.
Methods:
Patients with AOSD who were followed in our clinic between 2007 and 2020 were screened retrospectively. For the diagnosis of AOSD, all of the patients fulfilled Yamaguchi criteria. The demographic characteristics, baseline and post-treatment clinical findings and outcomes were reported.
Results:
Twenty-eight patients (21 F, 7 M) were screened (Figure 1). The mean disease duration of the first bDMARD was 21,76 ± 28,05 months (mean ± SD). The mean duration of bDMARD treatment was 37,04 ± 30,75 months. The reasons for starting a bDMARD were systemic symptoms (%80) and chronic arthritis (%20). All of the patients used methotrexate (MTX) except one. This patient had macrophage activation syndrome during diagnosis and was treated with cyclosporine. All of the patients were treated with corticosteroids (34,28 ± 26,70 mg/d) and a cDMARD at initiation (22 of them MTX, 1 of them azathioprine, 2 of them cyclosporine and 1 of them IVIg). Anakinra was the most preferred biologic as a first-line treatment modality (TNF inhibitors=5, tocilizumab=4). The main reason for switching was loss of efficacy (8/22). Tocilizumab was the most used agent in 2
nd
line and canakinumab was in 3
rd
line. Twenty-two patients were in remission at last visit. Also, 15 patients were steroid-free, 14 patients were MTX-free. Patient global visual analogue scale, acute phase reactants and daily steroid dose were reduced significantly at last visit compared to the initial visit (Table 1).
Table 1.
Comparison of important laboratory findings and the mean steroid dose
Clinical finding
At initiation of bDMARD
mean ± SD
At the last visit
mean ± SD
PG-VAS
9.8 ± 0.8
2.3 ± 2.3
ESR (mm/h)
34,28 ± 33,95
18.82 ± 11.60
CRP (mg/l)
70,76 ± 67,80
13.44 ± 27.33
Ferritin (ng/mL)
1662 ± 1239
275.7 ± 381.4
Daily steroid dose (prednisolone, mg/d)
34.28 ± 26.70
5.60 ± 8.60
Figure 1.
Presenting signs and the symptoms of the patients
bDMARD treatment was terminated in 5 patients due to complete remission (n=2) and side effects (1 of them pneumonia, 1 of them EBER (+) Hodgkin Lymphoma and 1 of them tuberculosis). Six patients experienced local injection site reaction, none of them stopped treatment. Also, one patient died while she was in remission under anakinra treatment with an unknown cause.
Conclusion:
The most common presenting symptoms in our cohort were fever and salmon-colored rash. Tocilizumab is an alternative treatment modality in cases with chronic arthritis and IL-1 inhibitors are an alternative for systemic course of disease. bDMARDs, especially IL-1 inhibitors are highly effective for refractory patients with AOSD.
Disclosure of Interests:
None declared
Background:
The importance of patient involvement in healthcare research is increasingly emphasized. Patients participate as research partners in designing studies and development of management ...recommendations, measurement tools and outcome measures. However, ensuring representation of the general patient population by specific patient groups may be challenging for multisystem diseases with heterogenous phenotype.
Objectives:
We aimed to evaluate whether patients with Behcet syndrome (BS) participating in a patient convention represent the actual patient population attending the clinic.
Methods:
A questionnaire was applied to 104 BS patients (Meeting group) attending the patient convention which was held during the Cerrahpasa Behcet Disease Symposium in Istanbul in February 2020. Patients had been invited to the convention through posters, advertisement on our website and social media. The questionnaire was conducted with a keypad given to the patients and it consisted of 21 items including age, gender, education level, working status, disease duration, BS manifestations, and treatment. The same questionnaire was filled by 97 consecutive patients (Clinic group) who attended our rheumatology outpatient clinic for their routine controls. Chi-square test was used to compare the groups.
Results:
Table 1 shows demographic and disease characteristics of the patient groups. The groups were similar in terms of sex and education level. There were more men in both groups, probably reflecting the more severe disease course among men in BS. There were significantly more patients who were >40 years of age and had a disease duration more than 20 years in the Meeting group. Although there were more patients who had a job in Clinic group, the difference was not significant. Central nervous system involvement, vascular involvement, genital ulcers, erythema nodosum, and arthritis were significantly more common in patients in the Meeting group compared with those in the Clinic group. The frequency of eye involvement, gastrointestinal involvement and papulopustular lesions were similar in the two groups. Cyclophosphamide use was significantly more common in Meeting group compared to the Clinic group.
Table 1.
Demographics, clinical characteristics, and treatments
Meeting Group
(n=104)
(n/N, %)
Clinic Group
(n=97)
(n, %)
P
Oral aphthous ulcers
88/97(91)
94(97)
0.13
Genital ulcers
86/104(83)
68(70)
0.045
Erythema nodosum
77/103(75)
47(48)
0.0003
Papulopustular skin lesions
69/103(67)
75(77)
0.09
Arthritis
78/102(77)
46(47)
<0.0001
Eye involvement
51/103(50)
53(55)
0.48
Vascular involvement
42/98(43)
25(26)
0.036
CNS involvement
14/103(14)
2(2)
0.016
GI involvement
14/97(14)
6(6)
0.10
Prednisolone - still using
30/104(29)
34(35)
0.37
Prednisolone - ever used
88/104 (85)
72(74)
0.08
Colchicine - still using
43/100 (43)
46(47)
0.57
Colchicine - ever used
86/100(86)
74(76)
0.10
AZA - still using
45/100 (45)
41(42)
0.77
AZA - ever used
81/100 (81)
74(76)
0.49
CYC - still using
1/96(1)
0(0)
NS
CYC - ever used
16/96(17)
7(7)
0.048
bDMARDs - still using
20/101(20)
26(27)
0.31
bDMARDs - ever used
28/101(28)
32(33)
0.44
* Adjusted
P
-values by Bonferroni correction were <0.001.
BS: Behcet Syndrome, CNS: Central nervous system, GI: Gastrointestinal, AZA: Azathioprine, CYC: Cyclophosphamide; bDMARDs: Biologic disease-modifying anti-rheumatic drugs; NS: non-significant
Conclusion:
Patients in the Meeting group had more severe disease compared to the Clinic group. Patients with all types of involvement were adequately represented in the Meeting group.
Disclosure of Interests:
None declared
BackgroundDespite methotrexate and steroid treatment, in cases of Adult-onset Still’s disease (AOSD) it is usually difficult to maintain clinic stability. In refractory cases, Anakinra treatment has ...been reported to be efficacious.1 ObjectivesIn this retrospective review, it is aimed to evaluate the AOSD cases treated with anakinra in our centre.MethodsFourteen AOSD patients (11 female,3 male) who were being followed in our outpatient clinic were reviewed retrospectively. The demographic characteristics, pre- and post-treatment clinical findings were reported.ResultsThe mean follow-up period of the patient population was 33.5±30.07 months (mean ±SD). Initial prednisolone dose was 37.3 mg/day. Except for one, all of our patients were exposed to methotrexate before being treated with anakinra. This patient was being treated with cyclosporine instead, since she had concomitant Macrophage Activation Syndrome. The other medications, the patients were previously treated with, were Etanercept (n=2), Tocilizumab (n=3), Infliximab (n=1) and Adalimumab (n=1).All patients were on 100 mgs of Anakinra, daily, except for the one treated with 200 mg/day. The mean duration of Anakinra therapy was 11.4 months. Among 7 patients in whom anakinra therapy was terminated, 1 had drug induced urticaria, 1 was primary irresponsive, 4 were secondary irresponsive and the other had severe pneumonia. Primary irresponsiveness is the lack of response to the therapy since the drug was first introduced, whereas in secondary irresponsiveness the case responds to the medication for a while and starts to flare again after asymptom-free period on the medication. Among 14, 7 of our patients are still on 100 mg/d Anakinra.The mean level of C reactive protein (CRP) measures was reduced from 64.38±61.95 mg/L to 34.3±24.3 mg/L with Anakinra therapy(p=0.003). Similarly, mean Erythrocyte Sedimentation Rate (ESR) was dropped to 33±22 mm/h from 59±35 mm/h by the help of the therapy(p<0.001). Among patients who primarily responded Anakinra therapy the mean Ferritin measures dropped to 427.25 ng/ml from 910 ng/ml (p=0.006). On the other hand, the Ferritin level was not significantly reduced in patients who did not respond Anakinra.The mean Patient reported Global Visual Analogue Scale (PG-VAS) score was also decreased to 3.83±4.7 from 9.5±0.07 following the therapy(p<0.001). Unfortunately, one of our 7 patients who were followed in remission under Anakinra died of an unknown etiology.ConclusionsAdult-onset Still’s disease is a challenging disorder, lacking a sufficient long-time clinical control. In order to obtain a full remission, various efforts have been spent so far. One of these approaches is to treat refractory cases with Anakinra, an IL-1 blocking agent. According to our clinical experience we state that, anakinra has a relatively high efficacy in controlling refractory cases.Reference1 Ortiz-Sanjuán F, et al. Efficacy of Anakinra in RefractoryAdult-OnsetStill’sDisease: MulticenterStudyof 41 PatientsandLiteratureReview. Medicine(Baltimore)2015Sep;94(39):e1554.Disclosure of InterestNone declared
BackgroundIn Adult-onset Still’s disease (AOSD), cases refractory to typical DMARDs, Canakinumab (an anti-IL-1ß monoclonal antibody) has been reported to be effective in a limited number of ...refractory cases.1 ObjectivesThe aim of this retrospective study was to represent AOSD patients treated with Canakinumab in 3 centres.MethodsThe follow up data of 10 AOSD patients (8 female, 2 male), who were followed up in outpatient clinics of 3 tertiary centres were reviewed retrospectively. The initial characteristics and follow up findings were reported.ResultsThe mean timespan between the initial diagnosis and Canakinumab treatment 45.2±29 months (mean ±SD). Before the onset of Canakinumab therapy, all patients were exposed to methotrexate, 1 to leflunomide, 8 to Tocilizumab and 8 to Anakinra. As for the biologic agents, 3 patients were also treated beforehand with Infliximab, 2 with Adalimumab, 2 with Etanercept and 2 with Rituximab. Canakinumab therapy was initiated in all patients with the indication of refractory disease under other medications, except for the one in whom neutropenia became evident under anakinra. The mean number of Canakinumab injections was 9.3±8. The mean follow-up period of patients treated with Canakinumab was 43.1±33 months. Seven out of 10 patients are still being treated with Canakinumab of 150 mg/month and one of 150 mg/every 2 months. One patient had a single injection and was fully controlled. The mean ferritin measure of 9 patients was reduced from 1292.3±1530 ng/ml to 354±530.2 ng/ml following the Canakinumab therapy (p=0.035). The mean of patient-reported global visual analogue scale (PG-VAS) scores was reduced from 7.4±2.4 to 2.3±2.2 with Canakinumab (p<0.001). Mean Erythrocyte sedimentation rate (ESR) was reduced from 44.2±35.1 to 22.7±26.5 with the help of Canakinumab therapy (p=0.005). Six patients are still on prednisolone at a maximum dose of 10 mg/day. The indication of therapy termination in the remaining 1 patient was the diagnosis of tuberculosis at 9th month of the treatment despite isoniazid prophylaxis. The patient was also treated with multiple biological agents beforehand, therefore it is not easy to conclude that treatment with Canakinumab induces tuberculosis flares.ConclusionsCanakinumab treatment seems to be effective in refractory AOSD patients who were previously treated with various agents. We state that an IL-1 blocking agent, Canakinumab is a relatively safe and effective alternative in managing refractory AOSD cases. On the other hand, randomised controlled trials are needed to further investigate the role of Canakinumab in these cases as well as its use as the first choice of biologic agents.Reference1 Kontzias A, Efthimiou P. The use of Canakinumab, a novel IL-1β long-acting inhibitor, in refractory adult-onset Still’s disease. Semin Arthritis Rheum2012;42(2):201–5.Disclosure of InterestNone declared
BackgroundLupus nephritis(LN) can be a cause of morbidity and mortality in a significant portion of patients. The treatment of lupus nephritis can be challenging in some patients who are resistant to ...conventional immunosuppressive treatment.ObjectivesRituximab is a promising agent for treating resistant LN patients. We evaluated the response of LN patients who were treated with rituximab treatment in our clinic retrospectively.MethodsWe evaluated LN patients who were followed and treated with at least one course of rituximab in our clinic between 2010-2022. LN was confirmed by renal biopsy. Creatinine clearence, serum creatinine, 24- hour proteinuria and Systemic Lupus Erythematosus- Disease Activity Index- 2000 (SLE-DAI-2K) were analyzed before and after Rituximab treatment. Primary end point was current prednisolone dose ≤5 mg and 24-hour proteinuria ≤ 500mg. Also, we evaluated the side effect of rituximab.ResultsForty seven patients (34 F, 13 M) were treated with rituximab. All patients had active lupus nephritis at initiation. Mean of disease duration was 10.44 ± 6.9 years. All patients were initally treated with high dose steroids. The other medications, the patients were previously treated with, were cyclophosphamide (n= 35), mycophenolate mofetil (n= 31), azathioprine (n= 6), cyclosporine (n= 2). Patients received an average of 4.1 ± 3.68 courses of rituximab (Table 1).The median value of pre-treatment proteinuria was 3050 (1370, 5175) mg/day. The median value of proteinuria after the final course was 747 (396, 1500) mg/day (p< 0.01). Serum creatinine level was changed from 0.94 ± 0.59 to 0.98 ± 0.68 (p= 0.53). Mean serum creatinine clearence was increased from 102.01 ± 43.2 to 109.1 ± 51.3 (p=0.28). Mean SLE-DAI-2K was reduced from 16.3 ± 6.2 to 7.2 ± 4.8 (p< 0.01). While initial steroid dose was 24.13 ± 18.47 mg/day, steroid dose at last rituximab course was 7.5 ± 5.8 mg/day (p< 0.01). End stage renal disease was developed in 3 (%6) patients.For primary end point of view, currrent prednisolone dose ≤ 5mg and 24-hour proteinuria ≤ 500 mg were achieved in %53.1, %36.1 of patients respectively. Both criteria was met by %25.5 of patients.During the treatment, 2 patients had serum reaction, 3 had pneumonia, 3 had herpes zoster. Three patients had hippogamaglobulinemia and treated with intravenous immunoglobulin. No one was died of lupus nephritis.ConclusionIn lupus nephritis patients resistant to conventional therapy, rituximab can be tried as an alternative treatment choice. In our single center, most of the patients were class IV nephritis whom we observed the efficacy of rituximab. Generally, the side effects were acceptable. Rituximab could be a good option as a steroid reducing agent and exhibit a favorable clinical response in these patients.Table 1.Characteristics of patientsAge, mean ± SD years42.3 ± 11.1Gender, n (%) Female Male34 (64.2) 13 (24.5)Disease duration, mean ± SD, years10.44 ± 6.9*ISN/RPS Classification, n (%) Class II Class III Class IV Class V Class III+V Class IV+V5 (10.6) 7 (14.8) 16 (34) 6 (12.7) 7 (14.8) 6 (12.7)RTX treatment courses mean ± SD4.1 ± 3.68Previous treatments, n Cyclophosphamide Mycophenolate mofetil Azathioprine Cyclosporine35 31 6 2*ISN/RPS Classification: International Society of Nephrology/Renal Pathology Society ClassificationREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.
Background:
The European League Against Rheumatism (EULAR) recommends pneumococcal 13-valent (PCV13) and 23-valent vaccines in patients with rheumatic diseases (1). Adverse reactions to 23-valent ...pneumococcal vaccine were previously reported in patients with Behçet Syndrome (BS) (2). These were proposed to be associated with the pathergy phenomenon which may be observed in patients with BS.
Objectives:
To determine the frequency of adverse reactions to PCV13 in patients with BS who were candidates for TNF inhibitor treatment, together with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) patients as controls.
Methods:
All of our patients who are candidates for TNF inhibitor therapy have been offered vaccination with PCV13 since 2016. We surveyed all patients with BS, AS and RA who were vaccinated with PCV13 in our infectious diseases outpatient clinic since 2016. Patients’ charts were reviewed and additionally patients were telephoned to identify any adverse local or systemic reactions. Local reactions were defined as redness, swelling, pain, and limitation of arm movement. Systemic reactions were defined as fever, headache, chills, rash, vomiting, joint pain, and muscle pain.
Results:
A total of 88 patients with BS, 143 patients with AS and 133 patients with RA had been vaccinated in our infectious diseases outpatient clinic. Among these, 55/88 (62%) patients with BS, 86/143 (60%) patients with AS and all 98/143 (68%) patients with RA could be contacted. Twenty-one of 55 (38%) patients with BS, 18/86 (20%) patients with AS and 27/98 (27%) patients with RA reported at least one local and/or systemic reaction after vaccination. Patients with BS reported more systemic reactions than the other two groups (48%, 12%, 23% respectively). On the other hand local reactions were less common among patients with BS (52%, 88%, 77% respectively). The local reactions were confined to erythema at injection site, pain and difficulty in moving among patients with AS and RA while 2 patients with BS had severe papulopustular skin lesions at injection site, in addition to erythema, pain and difficulty in moving. Both of these patients were pathergy positive at the time of the diagnosis.
Conclusion:
Severe papulopustular skin lesions at PCV13 injection site were observed only, but rarely, in patients with BS. Possibility of recall bias due to the retrospective nature of our study and the lack of other vaccines as controls are limitations of our study. Whether the skin lesions are caused by the skin pathergy reaction needs to be studied prospectively, as the pathergy status at diagnosis may be changed by the time these patients become candidates for TNF inhibitor treatment.
References:
1Furer V, Rondaan C, Heijstek MW, Agmon-Levin N, van Assen S, Bijl M, Breedveld FC, D’Amelio R, Dougados M, Kapetanovic MC, van Laar JM, de Thurah A, Landewé RB, Molto A, Müller-Ladner U, Schreiber K, Smolar L, Walker J, Warnatz K, Wulffraat NM, Elkayam O. 2019 update of EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis. 2020 Jan;79(1):39-52. doi: 10.1136/annrheumdis 2019-215882. Epub 2019 Aug 14. PubMed PMID: 31413005.
2Saeidinejad M, Kardash S, Connell L. Behcet’s disease and severe inflammatory reaction to 23-valent pneumococcal polysaccharide vaccine: a case report and review of literature. Scott Med J. 2018 Sep 25:36933018801215. doi: 10.1177/0036933018801215. Epub ahead of print PubMed PMID: 30253703.
Disclosure of Interests:
Berna Yurttas: None declared, Sitki Safa Taflan: None declared, Nese Saltoglu: None declared, Gulen Hatemi Grant/research support from: BMS, Celgene Corporation, Silk Road Therapeutics – grant/research support, Consultant of: Bayer, Eli Lilly – consultant, Speakers bureau: AbbVie, Mustafa Nevzat, Novartis, UCB – speaker
ObjectivesTo assess the colchicine compliance in patients diagnosed with Familial Mediterrenean Fever (FMF) related amyloidosis in our center.MethodsFourty one patients (18 male/23 female) were ...questioned with regards to colchicine compliance by using retrospective scanning of patient data.ResultsThe mean age at the symptomatic onset of FMF was 7.13±5.24 years. The mean age at the time of the FMF diagnosis was 21.21±14.85 years. The mean age at the initiation of colchicine treatment was 21.42±14.75 years and the mean age at time of the diagnosis of amyloidosis was found 29.57±12.14 years. Mean duration of the disease was 31.702±11.84 years and the duration of delayed diagnosis was 14.35±13.84 years. Maximum dose of colchicine was 2,103±0,673 mg/day. Compliance of colchicine treatment was poor in FMF related amyloidosis during their follow-up (11/25, %44), rates of skipped doses were also high (17/25, %68). Compliance rates were high in patients in whom FMF and amyloidosis were diagnosed simultaneously (12/13, %93), rates of skipped doses were also low (2/13, %14). One of the patients diagnosed with FMF after the diagnosis of amyloidosis was compliant, two of them were non-compliant; with regards to skipping doses, two patients were found to be compliant and therefore never skipped doses while one was skipping doses. The compliance to colchicine was high in all FMF patients once amyloidosis was evident (31/41, %75), and rates of skipped doses were also low (12/41, %30). In five FMF patients, amyloidosis was observed despite their compliance to treatment.ConclusionsThe overall delay of diagnosis in FMF patients with amyloidosis was found to be high. Particularly the FMF patients who were diagnosed with amyloidosis during their follow up were found to have lower rates of compliance. There were also a group of patients who were diagnosed with amyloidosis despite adequate and convenient colchicine treatment. It was emphasized that not only the early diagnosis and adequate treatment, but also the close follow up is important in managing FMF patients.Disclosure of InterestNone declared
Background
Behçet syndrome (BS) is a unique vasculitis that can affect arteries and veins of all sizes. Thrombosis is an important component of vascular involvement in BS. Although several studies ...were conducted to highlight the mechanism of thromboinflammation in BS, it is still not fully understood.
Objectives
We performed a systematic review and meta-analysis of studies investigating thrombotic, fibrinolytic, and endothelial factors in BS.
Methods
We searched PubMed and EMBASE with the keyword “Behcet*” in four languages (English, German, French and Turkish) from their inception up to April 2020. Titles and/or abstracts of all studies were screened independently by two reviewers (GGO and BY) and conflicts were solved by a third reviewer (GH). Studies comparing BS patients with and without thrombosis and studies comparing BS patients with thrombosis and patients with thrombosis due to other causes were analyzed separately. The pooled odds ratios (OR) with 95%CI were calculated for binary outcomes and standardized mean differences (MD) were calculated for continuous outcomes using RevMan 5.3. We categorized the factors into 4 groups based on acting mechanism 1- those that decrease anticoagulant activity 2- those that increase procoagulant activity 3- those that decrease the activity of fibrinolytic system 4- pathogenetic/endothelial factors.
Results
Of 15548 articles, 15157 were excluded due to duplication and inappropriate study design after reviewing titles and abstracts. Full text review of the remaining 391 articles yielded 103 papers meeting our predetermined inclusion criteria.
Factors significantly associated with BS thrombosis compared to BS without thrombosis were high frequency of factor V Leiden mutation (15 studies, OR 2.55, 95%CI 1.66-3.93), high homocysteine level (14 studies, MD: 4.27, 95%CI 2.31-6.22), high protein C level (5 studies, SMD: 0.80, 95%CI 0.15-1.45) and high alpha1-antitrypsin level (1 study, MD: 3.00, 95%CI 0.15-5.85) in Group 1; high factor 8 level (4 studies, MD: 17.17, 95%CI 7.79-6.55), high thrombin level (1 study, MD: 35.90, 95%CI 12.40-59.40), high neutrophil/lymphocyte ratio (2 studies, MD: 1.37, 95%CI 0.24-2.50) and high platelet/neutrophil complex level (1 study, MD: 10.50, 95%CI 0.76-20.24) in Group 2; high TAFI activity (1 study, MD: 28, 95%CI 4.12-51.88) in Group 3; high VEGF level (2 studies, SMD: 1.63, 95%CI 0.21-3.05), high CEC concentration (2 studies, SMD: 1.00, 95%CI 0.22-1.77), high MCP-1 level (1 study, MD: 74.16, 95%CI 61.29-87.03), high anti-C1q level (1 study, MD: 9.11, 95%CI 0.51-17.71), high platelet microaggregate formation (1 study, MD: 75.00, 95%CI 7.62-142.38), high frequency of P-selectin glycoprotein ligand 1 gen polymorphism (heterozygous (AB+AC+BC)) (1 study, OR: 1.88, 95%CI 1.07-3.31), high ADMA level (1 study, MD: 0.16, 95%CI 0.08-0.24), high sICAM-1 level (1 study, MD: 59.30, 95%CI 3.35-115.25) and low brachial artery flow-mediated (endotelium-dependant) dilatation (1 study, MD: -3.22, 95%CI -5.18--1.26) in Group 4.
Factors that were associated with BS thrombosis compared to thrombosis due to other causes including JAK-2 mutation, circulating endothelial cells, activated protein C resistance, tPA, and PAI were assessed in 1 study each. Among these, tPA levels (MD: -6.00, 95%CI -10.99--1.01), APCR (OR: 0.09, 95%CI 0.01-0.73) and JAK-2 mutations (OR: 0.01, 95%CI 0.00-0.06) were significantly less in patients with BS thrombosis compared to patients with thrombosis due to other causes.
Conclusion
Several factors were identified that may potentially be associated with thrombosis in BS. However, the cut-offs used for defining the normal level for these factors, time of blood collection (during acute or chronic stage of thrombosis, use of anticoagulants) and the type of thrombosis (arterial, venous, or cerebral sinus) were not uniform across the studies. Studies investigating these factors together, in a large number of patients, and together with appropriate controls are needed to confirm these results.
Disclosure of Interests
None declared
Background:
Oral ulcers, the hallmark lesion of Behçet’s syndrome (BS) can be disabling and impair eating, drinking and speaking. Despite recent advances in systemic medications for the treatment of ...oral ulcers, some patients do not achieve complete remission. Topical agents may help such patients by decreasing the pain and duration of oral ulcers. Pentoxyfilline (PTX) is a methylxanthine derivative that inhibits phosphodiesterase and is thought to have immunomodulatory effects in addition to improving blood flow which is its main reason for use in peripheral vascular disorders.
Objectives:
The aim of this study is to assess the efficacy and safety of PTX gel for oral ulcers in patients with BS. We also aimed to explore the best tools for the assessment of treatment response to topical agents in randomized controlled trials (Clinicaltrial.gov ID: NCT 03888846).
Methods:
This was an open-label, randomized, parallel group study comparing PTX gel in addition to colchicine (PTX-COL) with colchicine alone (COL). Patients with BS who were treated with colchicine and not using any other systemic medications for BS, having at least one oral ulcer that appeared during the last 48 hours were included. PTX 5% gel with a dose of 1000 mg/day was applied in 4 divided doses per day for 14 days. Patients were contacted daily for 14 consecutive days. Photographs were taken every 24 - 48 hours and graphical processing software was used to calculate the area of the index ulcer. Duration of the index ulcer, time to start of index ulcer shrinkage, time to 50% reduction in oral ulcer pain on a 10 mm visual analog scale (VAS), change from baseline in the area of the index ulcer over time, total number of oral ulcers and adverse events were evaluated.
Results:
A total of 41 patients were randomized, 39 patients (18 in the PTX-COL group and 21 in the COL group) completed the study and 2 patients in PTX-COL group withdrew from the study due to unacceptable dysgeusia and nausea. Mean duration of index ulcer, time to start of index ulcer shrinkage, time to 50% reduction in oral ulcer pain, and number of patients with no detectable ulcers on day 4 in each group were lower in the PTX-COL group as presented in the Table. Change from baseline in the area of index ulcer and pain score over time is shown in the Figure. There were no serious adverse events. Fifteen (75%) patients reported nausea, 11 (55%) reported dysgeusia and 2 reported vomitting in the PTX-COL group, while 2 patients (10%) reported nausea in the COL group.
Conclusion:
This pilot phase 2 open label, randomized controlled study supports the hypothesis that topical PTX in addition to colchicine accelerates the healing of BS oral ulcers compared to colchicine alone. A phase 3 controlled study with a higher number of patients is planned with improving the taste for tolerability of the product.
Disclosure of Interests:
Gulen Hatemi Grant/research support from: BMS, Celgene Corporation, Silk Road Therapeutics – grant/research support, Consultant of: Bayer, Eli Lilly – consultant, Speakers bureau: AbbVie, Mustafa Nevzat, Novartis, UCB – speaker, Berna Yurttas: None declared, Zekayi Kutlubay: None declared, Tim Cote Employee of: Silk Road Therapeutics is in Washington, DC, USA, Şemsi Burak Derkunt Employee of: Silk Road Therapeutics is in Washington, DC, USA, Yusuf Yazici: None declared, Hasan Yazici: None declared
BackgroundTocilizumab may be an alternative for patients with Behçet’s Syndrome (BS) refractory to conventional immunosuppressives and TNF inhibitors.ObjectivesWe aimed to report our experience with ...tocilizumab in patients with BS.MethodsWe identified BS patients who were treated with tocilizumab for eye, nervous system and arterial involvement, and amyloidosis, using our hospital’s electronic medical records. Demographic and clinical features, previous therapy, treatment response, outcomes, and adverse events were retrieved from patient charts.ResultsA total of 12 patients with BS (M/F: 9/3, mean age 44.4±10.3 years) were treated with tocilizumab for uveitis (n=6), parenchymal nervous system involvement (n=2), aortitis (n=2) and amyloidosis (n=2) between 2014-2022. Previous treatment modalities and treatment response for uveitis are shown in Table 1. Only 2 of the 6 patients with uveitis obtained remission with tocilizumab. Both patients with neurological involvement were refractory to tocilizumab treatment. They had previously used colchicine, steroids, azathioprine, interferon-alpha, infliximab, and adalimumab. Additionally, one had used cyclophosphamide and the other methotrexate and mycophenolate mofetil. One of the patients with amyloidosis was unresponsive and underwent kidney transplantation. The other had improvement in proteinuria, but she developed Crohn disease and infliximab was started. One patient with aortitis had used steroids, colchicine, azathioprine, cyclophosphamide, infliximab and the other had used steroids, colchicine, azathioprine, interferon-alpha and methotrexate. Both patients with aortitis obtained remission. One of them discontinued tocilizumab voluntarily, and the other due to dyslipidemia. Overall, tocilizumab was discontinued in 10/12 patients after 10.1±7.8 months. Adverse events were increased mucocutaneous lesions in one and dyslipidemia in another patient.ConclusionBS patients with aortitis benefitted from tocilizumab. However, our experience with tocilizumab in patients with eye and nervous system involvement was not as favorable as reported in previous case series. This may be partly due to the long disease duration before tocilizumab and the patient’s ‘being difficult-to-treat patients, refractory to several previous biologics including TNF inhibitors and interferon-alpha.References1Akiyama M, Kaneko Y, Takeuchi T. Effectiveness of tocilizumab in Behcet’s disease: A systematic literature review. Semin Arthritis Rheum. 2020 Aug;50(4):797-804.Table 1.Demographic and clinical features, previous and concomitant treatment in refractory Behçet’s uveitis patients treated with tocilizumab.NoSex/AgeUveitis duration before TCZ (year)Previous therapyIndicationsConcomitant medicationsNumber of attacksVA (before TCZ)VA (after TCZ)Response to TCZ treatmentRLRL1M/304cs, aza, CsA, ifn, inx, ada, czp, tacinductioncs, aza, CsA31/10CF at 3 mCF at 0.5 m2/10active2F/4415Cs, aza, CsA, ifn, inx, ada, mmf, czpinductioncs, CsA, mmf3TD4/10TD9/10active3*M/4518cs, aza, CsA, ifn, inxinductionAnti-tuberculosis01/101/101/102/10remission4¥M/351cs, aza, adaContraindication for TNF inhibitorscs, mmf010/1010/1010/1010/10remission5M/423cs, aza, CsA, ifn, inx, mmf, adainductioncs11/101/101/10HMactive6M/424colchicine, cs, aza, CsA, inx, anr, ifn, chlorambucilinductioncs55/10HM8/10LPactivecs: corticosteroids, aza: azathioprine, CsA: cyclosporine A, ifn: interferon alpha, inx: infliximab, ada: adalimumab, czp: certolizumab, tac: tacrolimus, mmf: mycophenolate mofetil, anr: anakinra, tcz: tocilizumab, VA: visual acuity, CF: counting fingers, m: meter, TD: terminal disease, HM: hand motion, LP: light perception, R: right, L: left*: The patient had pulmonary tuberculosis under infliximab treatment and was switched to tocilizumab. While uveitis was in remission, tocilizumab was discontinued due to the development of tuberculous lymphadenitis.¥: The patient had interstitial lung disease under infliximab treatment and was switched to tocilizumab.Acknowledgementsnone.Disclosure of InterestsNone Declared.
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