scholarly journals A case of effective use of interleukin 6 inhibitors in patients with ankylosing spondylitis with secondary amyloidosis

2021 ◽  
Vol 15 (4) ◽  
pp. 38-42
Author(s):  
Sh. F. Erdes ◽  
D. G. Rumyantseva ◽  
E. M. Agafonova ◽  
M. M. Urumova ◽  
A. S. Starkova ◽  
...  

Ineffectiveness of interleukin 6 inhibitors (iIL6), tocilizumab (TCZ) and sarilimumab in ankylosing spondylitis (AS) was shown in randomized clinical trials. However, there is ample evidence that IL6 is actively involved in the pathogenesis of this disease. In addition, the efficacy of iIL6 in patients with secondary AA-amyloidosis was established.Objective: to analyze the results of TCZ administration in AS, complicated by secondary AA-amyloidosis.Patients and methods. The analysis included 6 patients with AS with secondary AA-amyloidosis. All patients were HLA-B27 positive male. The average age of patients was 44±9.2 years, the average age of the disease onset was 16.3±7.9 years, the average duration of AS was 26.0±7.5 years. All 6 patients had pathomorphologic confirmed secondary AA-amyloidosis: all had kidney affection, 5 patients also had gastrointestinal tract affection and 2 had heart affection. As a first biological drug TCZ was prescribed in 2 patients, and 4 patients had previously received one or more inhibitors of tumor necrosis factor α. The average duration of TCZ treatment was 27.6 [3.0; 36.0] months.Results and discussion. During TCZ therapy, the level of CRP (M±σ) significantly decreased: from 81.1±74.5 to 1.2±0.8 mg/L (p<0.05), as well as daily proteinuria (Me [25th ; 75th percentile]): from 1.8 [1.0; 2.1] to 0.2 [0.1; 0.3] g/day (p<0.05) and AS activity indices – BASDAI (M±σ): from 6.2±1.6 to 3.3±0.9 (p<0.05 ); ASDAS-CRP (M±σ) from 4.6±1.1 to 2.04±0.7 (p<0.05). Positive dynamics was also noted in relation to a decrease in the number of patients with inflammatory back pain, arthritis and coxitis. A case of clinical and laboratory remission of AS on TCZ treatment is described. Conclusion. The presented data show that in certain clinical situations iIL6 can be highly effective in AS.

2021 ◽  
Vol 8 ◽  
Author(s):  
Per Eriksson ◽  
Johan Mölne ◽  
Lina Wirestam ◽  
Christopher Sjöwall

Historically, secondary amyloidosis has been a feared complication of chronic inflammatory conditions. The fibril protein AA derives from the acute phase reactant serum amyloid A (SAA). Long-term elevation of SAA levels remains a major risk factor for the development of AA amyloidosis in rheumatic diseases, and the prognosis may be unpredictable. Nowadays, with increased availability of effective biological agents, the incidence of AA amyloidosis seems to be declining. Still, genetically predisposed subjects with slowly progressive disease and mild symptoms combined with ongoing systemic inflammation may be at risk. Interleukin-6 (IL-6) is one of the drivers of SAA release and effectiveness of the humanized anti-IL-6 receptor antibody tocilizumab (TCZ) for the treatment of AA amyloidosis has been observed in some rheumatic conditions. Herein, we report two male subjects with longstanding ankylosing spondylitis (AS) complicated by renal amyloidosis who received TCZ with rapid and beneficial effects regarding inflammation and proteinuria. To the best of our knowledge, the use of TCZ in AS patients with this extra-articular manifestation has not previously been described. The paper includes histopathology, clinical follow-up, and longitudinal data of the two cases along with a comprehensive review of relevant literature. Mechanisms behind amyloid-mediated tissue damage and organ dysfunction are discussed. Altogether, our data highlight that blocking IL-6 signaling may represent a promising therapeutic option in patients with renal AA amyloidosis.


2020 ◽  
Vol 22 (1) ◽  
pp. 22-30
Author(s):  
Esteban Emiliani ◽  
Adrian Jara ◽  
Andres Koey Kanashiro

Background: Kidney stones are one of the oldest known and common diseases in the urinary tract with a prevalence that varies from 1% to 20%. Many phytotherapic and herbal medicines for kidney stones have been described for their treatment and prevention. Objective: The objective of this study is to perform a comprehensive review of several phytotherapic and herbal medicines published including clinical and animal studies. Results: Phytotherapy may influence the risk of recurrence in calcium oxalate and uric acid stones. The most solid evidence suggest that Phyllanthus niruri is one of the most studied components that appear to interfere with the calcium oxalate crystallization, reduced hyperoxaluria and hiperuricosuria and increased shock wave lithotripsy efficacy due to reduced crystallization without significant adverse effects, also Theobromine have shown to reduce the crystallization of uric acid in patients and appears to be a promising supplement to treat such stones. Conclusion: Many phytoterapic and herbal agents have been studies to treat and present urolithiasis, most of them only with studies of small number of patients or in animal models. Further randomized clinical trials are needed to evaluate the effect of these agents in kidney stones.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1612.2-1613
Author(s):  
J. M. Bello-Gualtero ◽  
O. J. Calixto ◽  
G. Salguedo ◽  
Y. M. Chamorro-Melo ◽  
C. A. Camargo Rodríguez ◽  
...  

Background:Spondyloarthritis refers to a family of diseases, of which ankylosing spondylitis and non-radiographic axial spondyloarthritis are responsible for axial impairment. Previously, the only treatment available were NSAIDs, which control activity and stop radiological progression, but at the expense of increased adverse effects, such as cardiovascular risk, dyspepsia and chronic renal failure. For the past 2 decades, biological therapy has been available, which means an increase in care costs.Objectives:The objective of this study is to perform a budget impact analysis of biologic therapy.Methods:To do a budget impact analysis from the perspective of the payer, comparing biological therapy with coventional therapy for the treatment of spondyloarthritis. Demographic characterization of the population attended at the Central Military Hospital. Time horizon from 2012 to 2018, taking the activity count according to the hospital’s billing and the prices of the activities of the state body SISMED. Exchange rates at the end of 2018.Results:The patients attended were 117, mostly men (63, 25%), average age 46, 4 years (SD 13), with disease diagnosis time of 9, 8 years (SD 9, 6). In the budget impact analysis, it is observed that 25% of patients were on DMARDs therapy, 22% with NSAIDs and 96% with biologic therapy. The average year/patient cost with NSAIDs alone would be EUR 381, with DMARDs only EUR 9,318 and, if only biological therapy was used, EUR 423. Within the total number of patients, the average annual cost, including the possibility of combining these drugs, amounted to EUR 5,403Conclusion:Including biological therapy in the care of patients with spondyloarthritis can increase up to 24 times the annual cost per patient. This increase is not only due to higher market value, it also relates to the need for more medical procedures and diagnostic follow-up tests.References:[1]Strömbeck, et al. Cost of Illness from the Public Payers’ Perspective in Patients with Ankylosing Spondylitis in Rheumatological Care. J Rheumatol 2010;37;2348-2355.Disclosure of Interests:None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1629.2-1629
Author(s):  
K. Ben Abdelghani ◽  
Y. Gzam ◽  
A. Fazaa ◽  
S. Miladi ◽  
K. Ouenniche ◽  
...  

Background:Axial spondyloarthritis (ax-SpA) is a chronic rheumatic disease that mainly affects men. However, the female form of ax-SpA remains insufficiently studied.Objectives:The aim of this study was to determine the clinical characteristics, the disease activity and the functional impact of female ax-SpA in comparison with male ax-SpA.Methods:This is a retrospective study including patients diagnosed with ax-SpA fulfilling the criteria of the Assessment of SpondyloArthritis international Society (ASAS) 2009.Clinical parameters, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Bath ankylosing spondylitis disease activity index (BASDAI) and Bath ankylosing spondylitis functional index (BASFI) were compared between groups of female and male ax-SpA.Results:Two hundred ax-SpA patients were included with 31% of female (n=62) and a mean age of 43,3 ± 11,2 years.The mean age at onset of symptoms was 31,8 ± 8,9 years for women and 25,3 ± 9,1 years for men (p <0,0001). The mean age at diagnosis was 36,4 ± 9,6 years for women and 31,7 ± 10,4 years for men (p = 0,003). Ax-SpA with juvenile onset was noted in 1,7% of women and 12,1% of men (p = 0,02). Male ax-SpA were significantly more smokers (46.8% vs 5.4%; p <0.001). The mean duration of morning stiffness was 11,3 ± 9,2 minutes for women versus 21,6 ± 19,3 minutes for men (p = 0,005).The mean ESR was 42,4 ± 29,8 mm for women and 28,3 ± 23,4 mm for men (p = 0,001). Radiographic sacroiliitis was present in 69,3% of women versus 84,7% of men (p = 0,01). The use of anti-TNF alpha was less frequent in women (29% vs 48,5%; p = 0,01).Our study didn’t found a statistically significant difference in peripheral manifestations, extraarticular manifestations, CRP, BASDAI and BASFI between the two groups.Conclusion:Female ax-SpA seems to have a better prognosis than male with older age in disease onset, less inflammation, less radiographic sacroiliitis and less use of biological treatments.References:[1]Rusman T, et al. Curr Rheumatol Rep. 2018; 20(6).[2]Siar N, et al. Curr Rheumatol Rev. 2019;Disclosure of Interests:None declared


2014 ◽  
Vol 04 (02) ◽  
pp. 136-139
Author(s):  
Deepak Hegde ◽  
Ballal Arjun ◽  
Vinay Kumar C. ◽  
H. Ravindranath Rai

Abstract:Ankylosing spondylitis (AS) is a chronic inflammatory disease that affects especially males in the second and third decades of life.1 The main clinical symptom is inflammatory back pain typically occurring at night and morning stiffness improving after exercise.1 Apart from syndesmophytes and ankylosis of the spine resulting in rigidity, in longstanding ankylosing spondylitis, also focal destructive 1 discovertebral lesions (Andersson lesions) can occur.1 The case we present here is of a 35 year old male patient who presented to us with the symptoms of pain of upper back and both shoulders for 6 years. Pain was followed with stiffness of the neck and shoulder. Radiography of the dorsolumbar spine revealed squaring of the vertebra, syndesmophytes, calcification of the anterior spinal ligament, end plate irregularity at D10-D11 level, ill defined sclerosis with fracture of the ankylosed spine, features consistent with Andersson lesion type III. He underwent posterior spinal fusion with good functional outcome.


Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 136 ◽  
Author(s):  
Levent Kilic ◽  
Abdulsamet Erden ◽  
Yusuf Sener ◽  
Berkan Armagan ◽  
Alper Sari ◽  
...  

Secondary amyloid A (AA) amyloidosis is a late and serious complication of poorly controlled, chronic inflammatory diseases. Rheumatoid arthritis (RA) patients with poorly controlled, longstanding disease and those with extra-articular manifestations are under risk for the development of AA amyloidosis. Although new drugs have proven to be significantly effective in the treatment of secondary AA amyloidosis, no treatment modality has proven to be ideal. To date, only in small case series preliminary clinical improvement have been shown with rituximab therapy for AA amyloidosis secondary to RA that is refractory to TNF-α inhibitors (TNF-i) therapy. In these case series, we assessed the efficacy and safety of rituximab therapy for patients with RA and secondary amyloidosis. Hacettepe University Biologic Registry was developed at 2005. The data of the RA patients who were prescribed a biological drug were recorded regularly. Patients with biopsy proven AA amyloidosis patients were screened. Of 1022 RA patients under biologic therapy, 0.7% patients had clinically apparent histologically confirmed amyloidosis. Four of seven patients who were prescribed rituximab at least one infusion enrolled to those case series. Two of four patients showed significant clinical improvement and one of them also had decrease in proteinuria and the other one had stable renal function and proteinuria. The main goal for the treatment of AA amyloidosis is to control the activity of the underlying disorder. In this study, we showed that rituximab may be an effective treatment in RA patients with amyloidosis who were unresponsive to conventional disease modifying anti-rheumatic drugs (DMARDs) and/or TNFi.


Acta Medica ◽  
2021 ◽  
pp. 1-6
Author(s):  
Selcan Demir ◽  
Müşerref Kasap Cüceoğlu ◽  
Yelda Bilginer

Objective: Enthesitis-related arthritis is a subtype of juvenile idiopathic arthritis category, characterized by enthesitis, arthritis, and the risk of axial involvement. We aimed to summarize the demographics, clinical, and laboratory findings of enthesitis-related arthritis patients and to identify the distinguishing features of enthesitis-related arthritis patients with HLA B27 positive compared to the patients who were HLA B27 negative. Materials and Methods: This retrospective study included patients with Enthesitis-related arthritis who followed up between 2015 and 2018. Demographical, clinical, and laboratory data were retrospectively reviewed from the patient files and computerized medical charts. Results: A total of 72 patients diagnosed with enthesitis-related arthritis were included in the study. The male/female ratio was 2.1/1. Fifty-three (73%) of them presented with peripheral arthritis. The most commonly affected joint was knee (81.1%), followed by the ankle (43%), hips (32%), and wrist (5%). HLA B27 was positive in 36 (50%) patients. During follow-up, the number of patients who developed enthesitis-related arthritis -associated uveitis was 8 (11.1%). During follow-up, 56 patients with inflammatory back pain and/or sacroiliac tenderness underwent spinal MRI. Ten (17.8%) patients had only thoracal and/or lumbar involvement, 18 (32%) had only sacroiliitis, and 9 (16%) patients had both of them on spinal MRI. In comparison with HLA-B27-negative children, HLA-B27-positive patients were more likely to have enthesitis (16 (44.4%) vs 8 (22.2%), p=0.046), MRI proven sacroiliitis (19 (52.7%) vs 8 (22.2%), p=0.031), MRI proven spinal involvement (13 (36.1%) vs 6 (16.6%), p=0.031), and uveitis (8 (100%) vs 0(0%), p=0.014). During follow up, 65/72 (90.2 %) of them needed disease-modifying antirheumatic drugs (DMARD), and 51/72 (70.8%) needed anti-tumor necrosis factor-α (TNF-α) therapy. Conclusion: We found that patients who were HLA-B27- positive had significantly more enthesitis, MRI-proven sacroiliitis, MRI-proven spinal involvement, and acute anterior uveitis, in comparison to patients who were HLA B27 negative. It is crucial to carefully assess those patients with concern for enthesitis-related arthritis to determine the expected prognosis and make therapeutic decisions appropriately.


2011 ◽  
Vol 139 (suppl. 1) ◽  
pp. 33-35 ◽  
Author(s):  
Petar Bilic ◽  
Ana Ivanis ◽  
Domagoj Vidovic ◽  
Vlado Jukic

Introduction. Psychiatric treatment in developed countries has significantly changed in the last few decades, with a significant shortening of the duration of hospitalization. Numerous West European countries are undertaking health system reforms to improve treatment efficiency. Objective. The aim of the study was to present the structure of hospitalized patients according to diagnostic categories of International Classification of Diseases and Related Health Problems - 10th Revision (ICD-10), and average duration of hospitalization from 2001 till 2010. Methods. Data was collected from hospital medical charts for the period from 2001 till 2010 on the number of hospitalized patients, diagnosis and duration of hospitalization. Results. Number of hospitalized patients increased by 27% (6309 vs. 8032). Average duration of hospitalization decreased for 45.1% (72.3 vs. 39.7 days), while the number of hospitalized patients decreased from 1284 (20.4%) in 2001 to 995 (12.4%) in 2010, the number of patients hospitalized because of depressive disorder increased from 309 (4.9%) in 2001 to 994 (12.4%) in 2010. The number of patients hospitalized because of enduring personality changes increased from 104 (1.7%) in 2001 to 449 (5.6%) in 2010. Conclusion. In the last decade the number of hospitalized patients suffering from schizophrenia at the Psychiatric Clinic Vrapce decreased, while the number of those suffering from depression and enduring personality change increased. The number of hospitalizations in the observed period increased overall. Observed changes can be explained by new therapeutic approaches, but also by objective social and economic factors and organization of the healthcare system.


2017 ◽  
Vol 177 (6) ◽  
pp. R287-R296 ◽  
Author(s):  
Wilmar M Wiersinga

About 5%–10% of hypothyroid patients on T4 replacement therapy have persistent symptoms, despite normal TSH levels. It was hoped that T4 + T3 combination therapy might provide better outcomes, but that was not observed according to a meta-analysis of 11 randomized clinical trials comparing T4 monotherapy with T4 + T3 combination therapy. However, the issue is still subject of much research because normal thyroid function tests in serum may not necessarily indicate an euthyroid state in all peripheral tissues. This review evaluates recent developments in the field of T4 + T3 combination therapy. T4 monotherapy is associated with higher serum FT4 levels than in healthy subjects, and subnormal serum FT3 and FT3/FT4 ratios are observed in about 15% and 30% respectively. T4 + T3 combination therapy may mimic more closely thyroid function tests of healthy subjects, but it has not been demonstrated that relatively low serum FT3 or FT3/FT4 ratios are linked to persistent symptoms. One study reports polymorphism Thr92Ala in DIO2 is related to lower serum FT3 levels after thyroidectomy, and that the D2-Ala mutant reduces T4 to T3 conversion in cell cultures. Peripheral tissue function tests such as serum cholesterol reflect thyroid hormone action in target tissues. Using such biochemical markers, patients who had a normal serum TSH during postoperative T4 monotherapy, were mildly hypothyroid, whereas those with a TSH 0.03–≤0.3 mU/L were closest to euthyroidism. Peripheral tissue function tests suggest euthyroidism more often in patients randomized to T4 + T3 rather than that to T4. Preference for T4 + T3 combination over T4 monotherapy was dose-dependently related to the presence of two polymorphisms in MCT10 and DIO2 in one small study. It is not known if persistent symptoms during T4 monotherapy disappear by switching to T4 + T3 combination therapy. The number of patients on T4 + T3 therapy has multiplied in the last decade, likely induced by indiscriminate statements on the internet. Patients are sometimes not just asking but rather demanding this treatment modality. It creates tensions between patients and physicians. Only continued research will answer the question whether or not T4 + T3 combination therapy has true benefits in some patients.


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