Patient perspectives on telemedicine use in rheumatology during the COVID-19 pandemic: survey results from the COVID-19 Global Rheumatology Alliance.

OBJECTIVE: The COVID-19 pandemic resulted in rapid adoption of telemedicine in rheumatology. We described perspectives of patients with rheumatic diseases related to telemedicine use. METHODS: An anonymous online survey for people with rheumatic diseases was launched in January 2021. We collected data on reasons for telemedicine use, perceived benefits, disadvantages and obstacles of telemedicine, perceived telemedicine effectiveness for different clinical tasks, level of satisfaction with telemedicine use, and future preferences for telemedicine. We summarized results with descriptive statistics and identified themes in free text responses to describe perspectives of telemedicine qualitatively. RESULTS: We received 596 complete responses (85% female and 47% 41-60 years old). During the COVID-19 pandemic, 78% (467/596) of respondents used telemedicine, and 61% (283/467) of telemedicine users reported that telemedicine was as effective or more effective than an in-person visit. Younger participants and those in North America reported effectiveness and satisfaction with telemedicine at higher frequencies. Participants reported similar effectiveness to in-person visits for making medication changes and discussing disease symptoms or complications. CONCLUSION: Most respondents found telemedicine at least as effective as in-person visits. Participants found telemedicine to be effective for specific scenarios, such as making medication changes and discussion of disease activity. Telemedicine may continue to be of importance in the care of patients with rheumatic diseases post pandemic, but likely for specific subsets of patients for specific visit indications. Key Points • Most patients with rheumatic disease found telemedicine as effective as in-person visits, particularly for some indications.

The clinical role of anakinra in the armamentarium against familial Mediterranean fever.

INTRODUCTION: Familial Mediterranean Fever (FMF) is the most common autoinflammatory disease that has mainly been treated with colchicine since 1972. A significant portion of patients do not respond to colchicine and require further treatment, mainly IL-1ß antagonists such as anakinra, canakinumab and rilonacept as IL-1ß has a crucial role in pathogenesis of FMF. This review summarizes the current approach to treating FMF and discovers the pharmacological and clinical utility of IL-1 blocking agents based on accumulated evidence with a focus on anakinra. AREAS COVERED: This review focuses on anakinra treatment in FMF. The data obtained from case reports, case series, retrospective studies and a Phase III trial are analyzed. Safety and efficacy profiles of anakinra are discussed. EXPERT OPINION: Anakinra is the cheapest anti-IL-1 agent used in the treatment of colchicine-resistant FMF. It is shown to be effective and safe when used in adjunct to colchicine however its short half-life and potential to cause injection site reactions limit its use.

Features predicting colchicine efficacy in treatment of children with undefined systemic autoinflammatory disease: A retrospective cohort study.

OBJECTIVE: Patients with undefined systemic autoinflammatory diseases (uSAIDs) are challenging to manage, as there are no guidelines or recommendations for targeted therapy. We aimed to evaluate the efficacy of empiric treatment with colchicine in our single-center uSAID population in the United States, as well as the patient characteristics associated with the most robust colchicine response. METHODS: Children with uSAID 18 years old at initial evaluation during 2000-2019 were included if they received 3 months of colchicine therapy. Data on demographics, clinical features, laboratory/ genetic studies, and treatment responses were collected. Most statistics were based on chi-square analyses for categorical data. Complete response to colchicine was defined as resolution of episodes or the presence of minor residual symptoms that did not require any further therapy. A partial response was defined as a decrease in the frequency, severity, or length of episodes but still necessitating additional therapy. Patients were considered nonresponders if they did not experience any improvement with colchicine at target therapeutic dosing. RESULTS: We identified 133 children diagnosed with uSAID who met our inclusion criteria. The median time to starting empiric colchicine was 5 months from the diagnosis of autoinflammatory disease. 92.5% (n = 123) of patients had a beneficial response to colchicine, including 46.6% (n = 62) partial responders and 45.9% (n = 61) complete responders. The presence of a nonurticarial rash was associated with an incomplete colchicine response (29.2% (n = 21) vs 13.1% (n = 8), P = .025). The presence of a heterozygous MEFV mutation in patients who did not fit Familial Mediterranean Fever diagnostic criteria (n = 25) appeared to be associated with a greater likelihood of complete colchicine response, although this was not statistically significant (62.5% (n = 14) vs 42.6% (n =11), P = .08). In MEFV mutation-negative patients, a nonurticarial rash was even more strongly associated with incomplete colchicine response, with an OR of 27.53 (CI [1.59-477], P = .023). The presence of oral ulcers also corresponded to incomplete colchicine response, although this did not reach clinical significance (38.9% (n = 28) vs 24.6% (n = 15), P = .08). There was no significant association between episode duration or frequency and colchicine response. CONCLUSION: Colchicine leads to clinical benefits in most children with uSAID. We, thus, recommend an early trial of colchicine in newly diagnosed patients with uSAID.

Late-onset familial mediterranean fever: single-center experience and literature review.

Familial Mediterranean fever (FMF) is a hereditary, autoinflammatory disease characterized by recurrent fever and serositis attacks. The disease onset occurs before 20 years of age in 90% of patients and rarely after the 4th decade. The aim of this study is to screen our FMF patient pool for patients with disease onset after age of 40 and to compare them to patients with early onset with regard to clinical and genetic features. The charts of 2020 patients registered in our FMF center in the years 2008-2017 were screened with regard to age of disease onset. Patients with disease onset after the age of 40 were considered as late-onset group (Group 1). The control group (Group 2) consisted of patients with a disease onset before the age of 20 who were randomly selected from the patient pool with twice the number of probands. Demographic, clinical and genetic data were recorded. Out of 2020 patients, the attacks of FMF had started after the fourth decade in 41 patients (2.02%), (Group 1). The male to female ratio was 1:1.7 in both groups. The delay of diagnosis was 5.6 ± 5.75 years in group 1, 10.7 ± 12.3 years in group 2. The only significant difference with regard to clinical features between two groups was the frequency of fever, which was present in 26 (63.4%) patients in group 1 and 67 (81.7%) in group 2 (p = 0.026). M694V mutation was more prevalent among early-onset group whereas exon 2 variants were more frequent in patients with late onset. The mean colchicine dose in the last 6 months was 1.38 ± 0.64 mg in group 1, and 1.61 ± 0.47 mg in group 2. FMF may start after 40 years of age in approximately 2% of the patients. Lower frequency of fever, lower daily colchicine dose and lower prevalence of exon 10 mutations point out that FMF patients with a disease onset after 40 years of age experience a milder disease compared to those with an onset before the second decade of life.

Rituximab as a glucocorticoid-sparing agent in idiopathic inflammatory myopathies: a retrospective single-center cohort study.

BACKGROUND: Idiopathic inflammatory myopathies (IIM) are essentially treated aiming to improve muscle function and extra muscular disease manifestations. Rituximab is potentially a glucocorticoid-sparing agent which was reviewed in multiple studies with small sample sizes due to the rarity of the disease. Higher statistical power can enhance the trustworthiness of alternative treatment modalities yielding the main objective of this study. METHODS: This retrospective study was conducted at a tertiary rheumatology center. Patients were diagnosed with an idiopathic inflammatory myopathy (dermatomyositis (DM), polymyositis (PM)) and were treated with rituximab to be included in this study. Parameters of disease activity including acute phase reactants, muscle enzyme levels, and disease-specific autoantibodies were analyzed. The primary study endpoint was the improvement of the patient symptoms. The secondary endpoint was the decrease in the creatinine kinase level. RESULTS: The study includes 26 patients (19 DM, 7 PM). The age of diagnosis was 42.04 ± 15.22 years; the follow-up duration was 64.84 ± 71.91 months. The mean corticosteroid dose decreased from 32.895 ± 24.399 to 8.44 ± 11.29 (p < 0.001). Other treatment methods were methotrexate (n = 18), intravenous immunoglobulin (IVIG) (n = 7), and cyclophosphamide (n = 2). Two patients were lost to follow-up. CONCLUSION: Rituximab is shown to be effective in treating myositis along with corticosteroids as well as a corticosteroid-sparing agent in retrospective studies and open-label clinical trials; however, lack of statistical power should be underlined. Long-term decrease in steroid use and decrease in disease activity markers hint the effective use of rituximab as a glucocorticoid-sparing agent as well as its safety with minimal side effects. Key Points • Long-term decrease in steroid use and decrease in disease activity markers hint the effective use of rituximab as a glucocorticoid-sparing agent as well as its safety with minimal side effects.

SARS-CoV-2 Infection and COVID-19 Outcomes in Rheumatic Diseases: A Systematic Literature Review and Meta-Analysis.

OBJECTIVE: The relative risk of SARS-CoV-2 infection and COVID-19 disease severity among people with rheumatic and musculoskeletal diseases (RMDs) compared to those without RMDs is unclear. This study was undertaken to quantify the risk of SARS-CoV-2 infection in those with RMDs and describe clinical outcomes of COVID-19 in these patients. METHODS: We conducted a systematic literature review using 14 databases from January 1, 2019 to February 13, 2021. We included observational studies and experimental trials in RMD patients that described comparative rates of SARS-CoV-2 infection, hospitalization, oxygen supplementation/intensive care unit (ICU) admission/mechanical ventilation, or death attributed to COVID-19. Methodologic quality was evaluated using the Joanna Briggs Institute critical appraisal tools or the Newcastle-Ottawa scale. Risk ratios (RRs) and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated, as applicable for each outcome, using the Mantel-Haenszel formula with random effects models. RESULTS: Of the 5,799 abstracts screened, 100 studies met the criteria for inclusion in the systematic review, and 54 of 100 had a low risk of bias. Among the studies included in the meta-analyses, we identified an increased prevalence of SARS-CoV-2 infection in patients with an RMD (RR 1.53 [95% CI 1.16-2.01]) compared to the general population. The odds of hospitalization, ICU admission, and mechanical ventilation were similar in patients with and those without an RMD, whereas the mortality rate was increased in patients with RMDs (OR 1.74 [95% CI 1.08-2.80]). In a smaller number of studies, the adjusted risk of outcomes related to COVID-19 was assessed, and the results varied; some studies demonstrated an increased risk while other studies showed no difference in risk in patients with an RMD compared to those without an RMD. CONCLUSION: Patients with RMDs have higher rates of SARS-CoV-2 infection and an increased mortality rate.

Effects of vitamin supplements on clinical cardiovascular outcomes: Time to move on! - A comprehensive review.

BACKGROUND & AIMS: Vitamin supplementations have increasingly been advertised on media and reported to be widely used by the general public to improve cardiovascular health. Due to the COVID-19 pandemic, people have become more interested in ways to improve and maintain their health. Increased awareness of people on healthy lifestyle is translating into inquisition regarding dietary supplements. AIM: First, focus on the most commonly used vitamin supplements and comprehensively review the evidence for and against recommending them to patients to improve and/or maintain cardiovascular health. Second, illustrate how the interest in studies shifted over time from Vitamin A, E, C, and B to Vitamin D and observational studies led to randomized controlled trials. METHODS: A thorough PubMed search with the phrase: "Vitamin supplements and cardiovascular health" was performed. In the present review, focus was maintained on the evidence for the use of vitamin supplements in the prevention of major cardiovascular events and/or the maintenance of cardiovascular health by comprehensively reviewing all previous studies indexed in PubMed. Studies with clinical 'hard' end-points were included only. RESULTS: A total of 87 studies met the inclusion criteria and were reviewed in the present article. High-quality evidence suggesting benefits for the use of vitamin supplements to maintain or improve cardiovascular health in people is minimal to non-existent. CONCLUSIONS: Vitamin supplementation does not improve clinical cardiovascular outcomes in general population. Counseling on the importance of maintaining a healthy lifestyle with adequate and nutritious food intake seems more appropriate to improve and maintain cardiovascular health.

Hydroxychloroquine for the treatment of COVID-19 and its potential cardiovascular toxicity: Hero or villain?

A variety of treatment modalities have been investigated since the beginning of the Coronavirus Disease-19 (COVID-19) pandemic. The use of antimalarials (hydroxychloroquine and chloroquine) for COVID-19 treatment and prevention has proven to be a cautionary tale for widespread, off-label use of a medication during a crisis. The investigation of antimalarials for COVID-19 has also been a driver for a deluge of scientific output in a short amount of time. In this narrative review, we detail the evidence for and against antimalarial use in COVID-19, starting with the early small observational studies that influenced strategies worldwide. We then contrast these findings to later published larger observational studies and randomized controlled trials. We detail the emerging possible cardiovascular risks associated with antimalarial use in COVID-19 and whether COVID-19-related outcomes and cardiovascular risks may differ for antimalarials used in rheumatic diseases.

Soluble TREM-1 Levels in Familial Mediterranean Fever Related AA-Amyloidosis.

Objectives: Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) is a monocyte and neutrophil receptor functioning in innate immunity. TREM-1 activity has been studied in various autoimmune diseases such as RA and SLE but there is no data in autoinflammatory pathologies. We studied soluble TREM-1 (sTREM-1) activity in Familial Mediterranean Fever (FMF) cases to evaluate the clinical role of TREM-1 in amyloidosis. Methods: The study includes 62 patients with FMF (42 with amyloidosis) who are regular attendees of a tertiary center for autoinflammatory diseases. For control purposes, 5 patients with AA amyloidosis secondary to other inflammatory diseases, and 20 healthy individuals were also included. Soluble TREM-1 levels were measured using enzyme-linked immunosorbent assay (ELISA). All FMF patients were in an attack-free period during the collection of the blood samples.Results: Soluble TREM-1 levels were found to be significantly higher in the FMF amyloidosis group compared to FMF without amyloidosis group and healthy controls (p = .001 and 0.002). Nevertheless, this difference between sTREM-1 levels was not found among FMF amyloidosis and other AA amyloidosis groups (p = .447) as well as between only FMF patients and healthy controls (p = .532). Soluble TREM-1 levels were found in correlation with creatinine and CRP in the FMF patient group regardless of their amyloidosis diagnosis (r = 0.314, p = .013; r = 0.846, p < .001).Conclusion: TREM-1 seems to be related to renal function rather than disease activity in FMF. Its role as an early diagnostic marker of amyloidosis in FMF complicated with AA amyloidosis should be tested in larger patient groups.

Anakinra treatment in patients with familial Mediterranean fever: a single-centre experience.

OBJECTIVES: Anakinra is proven to be effective in controlled trials in terms of attack frequency and subclinical inflammation in colchicine-resistant patients. The objective of this study was to review the patients followed in our single centre with FMF who received anakinra because of insufficient colchicine response. METHODS: The study was conducted at a tertiary rheumatology centre experienced in autoinflammatory diseases. The patients were treated for at least 1 month with anakinra. Patients with amyloidosis and pregnancy were not included. Attack frequency, patient global assessment scales of disease severity and acute phase reactants were recorded before and throughout anakinra treatment. Criteria of treatment termination were side effects, disease remission, inadequate response, pregnancy plan and non-compliance. RESULTS: One hundred and six patients diagnosed with FMF were treated with anakinra; 45.92% of the patients had a homozygous M694V mutation; 83 of the 98 patients tested for MEFV carried at least one copy of M694V. Attack frequency decreased while on anakinra treatment; in fact, no attacks were observed in 75 patients. Visual analogue scale score decreased from 7.49 (2.03) to 3.08 (2.82) (P = 0.001). Currently, 71 patients are still on anakinra treatment. Treatment of 34 patients was discontinued (32%). Insufficient response and side effects were the most common reasons for treatment discontinuation. All of the side effects observed were reversible and the patients alleviated after treatment cessation. In four patients, leukopenia was observed. CONCLUSION: In patients who were refractory to colchicine, anti-IL-1 agent anakinra was shown to be effective and safe. The effectiveness of anakinra stems from preventing attacks and increasing the quality of life.

Inflammatory hypothesis of atherogenesis: Will colchicine be added to the armamentarium in the prevention of coronary artery disease?

Chronic inflammation promotes the development and progression of atherosclerosis. Despite aggressive risk reduction, patients with coronary artery disease have a significant residual risk of myocardial infarction and cardiovascular death related in part to ongoing inflammation within coronary vasculature. In this review, we summarize the clinical trials that provide evidence for the inflammatory hypothesis of atherogenesis. Additionally, we describe studies suggesting colchicine may be able to reduce residual inflammatory risk via the NLRP3 pathway. Given its tolerable side effect profile, safety, and low cost, colchicine holds promise as an anti-inflammatory agent in primary and secondary prevention of coronary disease.

Familial Mediterranean Fever: Clinical State Of The Art.

As the inflammation research improves year by year, so does our understanding of the autoinflammatory conditions. Over the past years, the number of monogenic autoinflammatory conditions snowballed thanks to our understanding of basic immunology and genetics. Familial Mediterranean Fever (FMF), being the entrance to this fascinating world, still has clinical relevance as it enables us to understand our approach to these patients, treatment modalities, and pathological mechanisms. This review can be used as a tool for clinicians already working with FMF patients to update themselves on recent scientific literature.

Safety and efficacy of anti-interleukin-1 treatment in 40 patients, followed in a single centre, with AA amyloidosis secondary to familial Mediterranean fever.

OBJECTIVE: The main devastating complication of FMF is AA amyloidosis. Approximately 10-15% of the patients are either intolerant or have an insufficient response to colchicine treatment. The most promising alternative treatment approach is anti-IL-1 agents. The aim of this study was to evaluate the efficacy and safety of anti-IL-1 therapy in FMF amyloidosis. METHODS: Forty-four patients with amyloidosis who had been treated with anti-IL-1 agents, anakinra and/or canakinumab, were assessed retrospectively for efficacy and safety. Five patients were on haemodialysis and four had received a renal transplant. RESULTS: The mean duration of anti-IL-1 treatment was 21.4 (18) months. Among 35 patients who were not on dialysis, renal function was maintained or improved in 79.4% but deteriorated in 20.6%. Patients with creatinine levels below 1.5 mg/dl at onset benefitted more from IL-1 inhibition with regard to their kidney functions and acute phase reactants. No additional side effects were observed in patients with renal replacement treatments. The major side effect of anakinra was injection-site reaction observed in four patients. CONCLUSION: Anti-IL-1 agents are well tolerated and effective in the treatment of amyloidosis secondary to FMF, including patients on dialysis and renal transplant recipients. This approach may improve the lifespan of transplanted kidneys in FMF patients.

The Prevalence of Familial Mediterranean Fever and Behçet's Disease: A Cross-Sectional Study.

OBJECTIVES: This study aims to investigate the coexistence of familial Mediterranean fever (FMF) and Behçet's disease (BD). PATIENTS AND METHODS: This cross-sectional study was conducted between May 2009 and August 2009. The study included 14,881 randomized children (7,741 males, 7,140 females; mean age 13.0 years; range, 12 to 14 years) from sixth to eighth grades, in 72 primary schools in the center of Turkey's Sivas province. Of these children, 985 were randomly selected and interviewed with their parents. During these interviews, the family trees up to second-degree relatives were drawn. The presence of a diagnosis of FMF or BD was questioned. Patient history, physical examination, eye examination, and pathergy test were performed when needed. The methods of this study were reported in accordance with the STrengthening the Reporting of OBservational studies in Epidemiology guidelines. RESULTS: Nine hundred and eighty-five students, 978 mothers, 953 fathers, and 1,876 relatives (4,792 in total) were included in the study. The ratio of consanguineous marriage ratio was 13.6%. Only 30 patients (0.6%) were diagnosed with FMF, while three (0.06%) were diagnosed with BD. In patients with FMF, consanguineous marriage was statistically significant (p=0.015). In terms of low back, heel, and joint pain and morning stiffness, there was a statistically significant difference between patients with and without FMF (p<0.05). Of the three BD patients, one had concomitant FMF. CONCLUSION: The prevalence of FMF in Sivas province was higher than Turkey's prevalence; however, the prevalence of BD was lower. According to these findings, it is not easy to conclude that the two diseases share a common pathogenesis.