scholarly journals Tuberculosis in biologic-naïve patients with rheumatoid arthritis - risk factors and tuberculosis characteristics

2021 ◽  
pp. jrheum.201251
Author(s):  
Johanna Karlsson Sundbaum ◽  
Elizabeth V. Arkema ◽  
Judith Bruchfeld ◽  
Jerker Jonsson ◽  
Johan Askling ◽  
...  

Objective To investigate risk factors and characteristics of active tuberculosis (TB) in biologics-naïve rheumatoid arthritis (RA) patients. Methods Population-based case-control study using the Swedish Rheumatology Quality Register, the National Patient Register and the Tuberculosis Register to identify RA cases with active TB and matched RA controls without TB 2001-2014. Clinical data were obtained from medical records. TB risk was estimated as adjusted (adj) odds ratios (OR) with 95% confidence intervals (CI) using univariate and multivariable logistic regression analyses. Results After validation of diagnoses, the study included 31 RA cases with TB, and 122 matched RA controls. All except three cases had reactivation of latent TB. Pulmonary TB dominated (84%). Ever use of methotrexate was not associated with increased TB risk (adj OR 0.8; 95% CI 0.3-2.0), whereas ever treatment with leflunomide (adj OR 6.0; 95% CI 1.5-24.6), azathioprine (adj OR 3.8; 95% CI 1.1-13.8) and prednisolone (adj OR 2.4 (95% CI 1.0-5.9) was. There were no significant differences of maximum dose of prednisolone, treatment duration with prednisolone before TB, or cumulative dose of prednisolone the year before TB diagnosis between cases and controls. Obstructive pulmonary disease was associated with an increased TB risk (adj OR 3.9; 95% CI 1.4-10.7). Conclusion Several RA-associated factors may contribute to the increased TB risk in biologics-naïve RA patients, making risk of TB activation difficult to predict in the individual patient. To further decrease TB in RA patients, the results suggest that screening for latent TB should also be considered in biologics-naïve patients.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 969.2-969
Author(s):  
J. Sundbaum ◽  
E. Arkema ◽  
J. Bruchfeld ◽  
J. Jonsson ◽  
J. Askling ◽  
...  

Background:The risk of tuberculosis (TB) has decreased in biologic disease modifying anti-rheumatic drugs (bDMARDs) treated rheumatoid arthritis (RA) patients, but remains unaltered 4-fold increased in bio-naïve RA patients compared to the general population in Sweden (1). In absolute numbers, most TB cases in contemporary RA patients occur in the group of bio-naïve patients. Knowledge about risk factors for TB and TB characteristics in bio-naïve RA patients is still limited.Objectives:To investigate risk factors for TB and TB characteristics in bio-naïve RA patients.Methods:Population-based case-control study. A national bio-naïve RA cohort was identified from the National Patient Register and the Swedish Rheumatology Quality Register. RA cases with TB were identified by linkage to the Swedish Tuberculosis Register (with mandatory TB registration) 2001-2014 (n=42). For each case, four matched RA controls without TB were identified. Clinical data were obtained from medical records. Univariate and multivariable logistic regression analyses were used to estimate risk for TB expressed as adjusted (adj) odds ratio (OR) with 95% confidence intervals (CI).Results:After review of the medical records and validation of diagnoses, 31 cases with RA and TB and 122 controls remained in the study. The TB cases had a median of 3 (1-6) reported TB risk factors, and almost 90% were born before 1950. Only one case was screened for TB (with negative result of tuberculin skin test). Active TB occurred at a mean of 15 years after RA diagnosis, and all except three cases were considered as reactivation of latent TB. Exposure to leflunomide (5 cases, 4 controls) (adj OR 6.02; 95% CI 1.47-24.65) and azathioprine (5 cases, 6 controls) (adj OR 3.85; 95% CI 1.06-13.79) were associated with increased risk for TB. Methotrexate, used in 67.7% of cases and 73.9% of controls, was not associated with increased risk of TB (adj OR 0.83; 95% CI 0.34-1.98). Exposure to corticosteroids was more common among cases than controls (74.2% vs 53.8%, p= 0.04), and was associated with an adj OR for TB of 2.44 (95% CI 1.00-5.92). No significant differences were identified between prednisolone-treated cases and controls in terms of maximum dose ever of prednisolone, treatment duration before TB, or cumulative dose of prednisolone during the last year before diagnosis of TB. Obstructive pulmonary disease was the only comorbidity linked to an increased TB risk (adj OR 3.94; 95% CI 1.45-10.69). Pulmonary TB dominated (84%) followed by TB lymphadenitis (19%). Treatment success was 94%, comparable to TB patients in general.Conclusion:Several RA-associated risk factors may contribute to increased TB risk in bio-naïve RA patients (treatment with leflunomide, azathioprine, or prednisolone and concomitant obstructive lung disease). We could not confirm previous findings of an association with the use of moderate to high doses of prednisolone (≥15 mg). TB risk seems difficult to predict with precision in the individual bio-naïve patient based on RA-associated risk factors. To further decrease the TB risk in RA patients TB screening should also be considered in the group of bio-naïve patients.References:[1] Arkema EV et al. Are patients with rheumatoid arthritis still at an increased risk of tuberculosis and what is the role of biological treatments? Ann Rheum Dis 2015;74:1212-17.Disclosure of Interests:Johanna Sundbaum: None declared, Elizabeth Arkema: None declared, Judith Bruchfeld: None declared, Jerker Jonsson: None declared, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma, Eva Baecklund: None declared


2018 ◽  
Vol 109 (2) ◽  
pp. 96-101 ◽  
Author(s):  
C. Odensten ◽  
K. Strigård ◽  
M. Dahlberg ◽  
U. Gunnarsson ◽  
P. Näsvall

Background: Parastomal hernia is common, but there are few population-based studies showing the frequency and outcome of parastomal hernia repair in routine surgical practice. The aim of this study was to identify patients undergoing surgery for parastomal hernia in Sweden and to define risk factors for complication and recurrence. Methods: A broad search of the Swedish National Patient Register 1998–2007 for all possible parastomal hernia repairs using surgical procedure codes. Records of all patients identified were reviewed and those with a definite parastomal hernia procedure were included and analyzed. Results: A total of 71 patients were identified after review of the records. The most common reason for surgery was cosmetic and the most frequent method was relocation of the stoma. Parastomal hernia recurrence rate was 18% during follow-up of a minimum 2 years. Overall, a surgical complication occurred in 32%. Possible risk factors were analyzed including emergency surgery versus planned, gender, age, indication for surgery, and method of surgery; none of which was significant. Conclusion: The frequency of parastomal hernia procedures was much lower than suggested by previous studies. The number of procedures per surgeon was even lower than expected. No specific risk factor could be identified. Parastomal hernia auditing in the form of a nationwide quality register should be mandatory. Centralization should be considered.


2018 ◽  
Vol 77 (7) ◽  
pp. 970-972 ◽  
Author(s):  
Anna Karin Hedström ◽  
Lars Klareskog ◽  
Lars Alfredsson

IntroductionSmoking has consistently been associated with increased risk of developing rheumatoid arthritis (RA). The aim of this study was to estimate the influence of passive smoking on the risk of developing anti-cyclic citrullinated peptide antibodies (ACPA)-positive and ACPA-negative RA.MethodsA population-based case–control study using incident cases of RA was performed in Sweden, and the study population in this report was restricted to include never-smokers (589 cases, 1764 controls). The incidence of RA among never-smokers who had been exposed to passive smoking was compared with that of never-smokers who had never been exposed, by calculating the OR with a 95% CI employing logistic regression.ResultsNo association was observed between exposure to passive smoking and RA risk (OR 1.0, 95% CI 0.8 to 1.2 for ACPA-positive RA, and OR 0.9, 95% CI 0.7 to 1.2, for ACPA-negative RA). No suggestion of a trend between duration of passive smoking and RA risk was observed.DiscussionsNo association was observed between exposure to passive smoking and RA risk, which may be explained by a threshold below which no association between smoke exposure and RA occurs.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 322-322
Author(s):  
B. Samhouri ◽  
R. Vassallo ◽  
S. Achenbach ◽  
V. Kronzer ◽  
J. M. Davis ◽  
...  

Background:Rheumatoid arthritis (RA) is a systemic inflammatory disease of the joints and other organs, including the lungs.1 Interstitial lung disease (ILD) is a lung injury pattern associated with significant symptom burden and poor outcomes in RA.2 Better understanding of its risk factors could help with disease prevention and treatment.Objectives:Using a population-based cohort, we sought to ascertain the incidence and risk factors of RA-associated ILD (RA-ILD) in recent years.Methods:The study included adult residents of Olmsted County, Minnesota with incident RA between 1999 and 2014 based on the 1987 ACR classification criteria.3 Study subjects were followed until death, migration, or 4/30/2019. ILD was defined by the presence of bilateral interstitial fibrotic changes (excluding biapical scarring) on chest computed tomography (CT). In the absence of chest CT imaging, a physician’s diagnosis of ILD in conjunction with chest X-ray findings suggestive of ILD and a restrictive pattern on pulmonary function testing (defined as a total lung capacity less than the lower limit of normal) was considered diagnostic of ILD. Evaluated risk factors included age, sex, calendar year, smoking status, body mass index (BMI) and presence/absence of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). Cumulative incidence of ILD was adjusted for the competing risk of death. Cox models were used to assess the association between potential risk factors and the development of RA-ILD.Results:In Olmsted County, 645 residents were diagnosed with RA between 1999 and 2014. Seventy percent of patients were females, and 30% were males; median age at RA diagnosis was 55.3 [IQR 44.1-66.6] years, and most patients (89%) were white. Fifty-three percent of patients were never-smokers, and 64% had seropositive RA. Forty percent were obese (i.e., BMI ≥30 kg/m2); median BMI was 28.3 [IQR 24.3-33.0] kg/m2.In the cohort, ILD was identified in 73 patients. The ILD diagnosis predated RA diagnosis in 22 patients (3.4%) who were excluded from subsequent analyses. Final analyses included the remaining 623 patients with no ILD preceding, or at the time of RA diagnosis. Over a median follow-up interval of 10.2 [IQR 6.5-14.3] years, 51 patients developed ILD. Cumulative incidence of ILD, adjusted for the competing risk of death, was 4.3% at 5 years; 7.8% at 10 years; 9.4% at 15 years; and 12.3% at 20 years after RA diagnosis (Figure 1).Age, and history of smoking at RA diagnosis correlated with the incidence of ILD; adjusted hazard ratios (HRs) were 1.89 per 10-year increase in age (95% confidence interval 1.52-2.34) and 1.94 (95% confidence interval 1.10-3.42), respectively. On the other hand, sex (HR: 1.21; 95% CI: 0.68-2.17), BMI (HR: 0.99; 95% CI: 0.95-1.04), obesity (HR: 0.89; 95% CI: 0.50-1.58), and seropositivity (HR: 1.15; 95% CI: 0.65-2.03) did not demonstrate significant associations with ILD.Conclusion:This study provides a contemporary estimate of the occurrence of ILD in a well-characterized population-based cohort of patients with RA. Our findings of a lack of association between sex, obesity and seropositivity with ILD may indicate a change in established risk factors for ILD and warrant further investigation.References:[1]Shaw M, Collins BF, Ho LA, Raghu G. Rheumatoid arthritis-associated lung disease. Eur Respir Rev. 2015;24(135):1-16. doi:10.1183/09059180.00008014[2]Bongartz T, Nannini C, Medina-Velasquez YF, et al. Incidence and mortality of interstitial lung disease in rheumatoid arthritis - A population-based study. Arthritis Rheum. 2010;62(6):1583-1591. doi:10.1002/art.27405[3]Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569-2581. doi:10.1002/art.27584Figure 1.Cumulative incidence of ILD in patients diagnosed with RA between 1999 and 2014, adjusted for the competing risk of death. Abbreviations. ILD: interstitial lung disease; RA: rheumatoid arthritis.Disclosure of Interests:Bilal Samhouri: None declared, Robert Vassallo Grant/research support from: Research grants from Pfizer, Sun Pharmaceuticals and Bristol Myers Squibb, Sara Achenbach: None declared, Vanessa Kronzer: None declared, John M Davis III Grant/research support from: Research grant from Pfizer., Elena Myasoedova: None declared, Cynthia S. Crowson: None declared


2021 ◽  
Vol 14 ◽  
pp. 117954412110287
Author(s):  
Mir Sohail Fazeli ◽  
Vadim Khaychuk ◽  
Keith Wittstock ◽  
Boris Breznen ◽  
Grace Crocket ◽  
...  

Objective: To scope the current published evidence on cardiovascular risk factors in rheumatoid arthritis (RA) focusing on the role of autoantibodies and the effect of antirheumatic agents. Methods: Two reviews were conducted in parallel: A targeted literature review (TLR) describing the risk factors associated with cardiovascular disease (CVD) in RA patients; and a systematic literature review (SLR) identifying and characterizing the association between autoantibody status and CVD risk in RA. A narrative synthesis of the evidence was carried out. Results: A total of 69 publications (49 in the TLR and 20 in the SLR) were included in the qualitative evidence synthesis. The most prevalent topic related to CVD risks in RA was inflammation as a shared mechanism behind both RA morbidity and atherosclerotic processes. Published evidence indicated that most of RA patients already had significant CV pathologies at the time of diagnosis, suggesting subclinical CVD may be developing before patients become symptomatic. Four types of autoantibodies (rheumatoid factor, anti-citrullinated peptide antibodies, anti-phospholipid autoantibodies, anti-lipoprotein autoantibodies) showed increased risk of specific cardiovascular events, such as higher risk of cardiovascular death in rheumatoid factor positive patients and higher risk of thrombosis in anti-phospholipid autoantibody positive patients. Conclusion: Autoantibodies appear to increase CVD risk; however, the magnitude of the increase and the types of CVD outcomes affected are still unclear. Prospective studies with larger populations are required to further understand and quantify the association, including the causal pathway, between specific risk factors and CVD outcomes in RA patients.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 973-973
Author(s):  
R. Gonzalez Mazario ◽  
J. J. Fragio-Gil ◽  
P. Martinez Calabuig ◽  
E. Grau García ◽  
M. De la Rubia Navarro ◽  
...  

Background:Cardiovascular disease (CV) is the most frequent cause of death in rheumatoid arthritis (RA) patients. It is well known that RA acts as an independent cardiovascular risk factor.Objectives:To assess the CV risk in RA patients using carotid ultrasonography (US) additionally to the traditional CV risk factors.Methods:A prospective transversal case control study was performed, including adult RA patients who fulfilled ACR/EULAR 2010 criteria and healthy controls matched according to CV risk factors. Population over 75 years old, patients with established CV disease and/or chronic kidney failure (from III stage) were excluded. The US evaluator was blinded to the case/control condition and evaluated the presence of plaques and the intima-media thickness. Statistical analysis was performed with R (3.6.1 version) and included a multivariate variance analysis (MANOVA) and a negative binomial regression adjusted by confounding factors (age, sex and CV risk factors).Results:A total of 200 cases and 111 healthy controls were included in the study. Demographical, clinical and US data are exposed in table 1. Not any difference was detected in terms of CV risk factors between the cases and controls. In both groups a relationship between age, BMI and high blood pressure was detected (p<0.001).Table 1.Table 2.RA basal characteristicsDisease duration (years)16,98 (11,38)Erosions (X-Ray of hands/feet)163 (81,5%)Seropositive (RF/anti-CCP)146 (73%)Extra-articular symptoms44 (22%)Intersticial difusse lung disease10 (5%)Rheumatoid nodules14 (7%)Prednisone use103 (51,5%)Median dose of Prednisone last year (mg)2,34 (2,84)sDMARDsMethotrexate104 (52%)Leflunomide29 (14,5%)Hydroxycloroquine9 (4,5%)bDMARDs89 (44,5%) TNFi41 (20,5%) Abatacept15 (7,5%) IL6i22 (11%) RTX11 (5,5%)JAKi26 (13%) Baricitinib11 (5,5%) Tofacitinib15 (7,5%)DAS 28-ESR3,1 (2,3, 3,9)SDAI7,85 (4,04, 13,41)HAQ0,88 (0,22, 1,5)RF (U/mL)51 (15, 164,25)Anti-CCP (U/mL)173 (22, 340)Patients showed higher intima-media (both right and left) thickness compared to controls (p<0.006). Moreover it was also related to the disease duration and DAS28 score (p<0.001). A higher plaque account was noted in cases(p<0.004) and it was also related to the disease duration (p<0.001).Conclusion:RA implies a higher CV risk. Traditional CV risk factors explains only partially the global risk. These findings support that RA acts as an independent cardiovascular risk factor.Disclosure of Interests:None declared


The Lancet ◽  
2017 ◽  
Vol 390 ◽  
pp. S85 ◽  
Author(s):  
Jiao Song ◽  
Angharad Walters ◽  
Damon Berridge ◽  
Ashley Akbari ◽  
Meirion Evans ◽  
...  

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