Tuberculosis In Rheumatoid Arthritis Patients Research Articles

Frequency of Smear Positive Pulmonary Tuberculosis in Rheumatoid Arthritis Patients Taking DMARDS at Khairpur Medical College/Hospital Khairpur

Background and Aim: The clinical tuberculosis infection risk increases with rheumatoid arthritis and its medication. Chronic systemic inflammation caused by rheumatoid arthritis is an autoimmune disease may affect various organs and tissues. The present study was aimed to assess the frequency of smear positive pulmonary tuberculosis in rheumatoid arthritis patients taking DMARDS at Khairpur Medical College/ Hospital Khairpur. Methodology: This cross-sectional study was conducted on 249 smear positive pulmonary tuberculosis in rheumatoid arthritis patients at the Department of Internal Medicine of Khairpur Medical College/Hospital Khairpur from March 2019 to July 2021. All the patients with cough for >3 weeks were enrolled by taking three sputum sample and risk assessment questionnaire. The Mycobacterium tuberculosis bacilli presence was identified based on acid fast staining technique. Tuberculosis incidence, medical records, and clinical manifestation were explored. SPSS version 24 was used for data analysis. Results: Of the total 249 patients, 226 (90.8%) were male and 23 (9.2%) were females. The overall mean age was 65.73±7.53 years. The incidence of tuberculosis with rheumatoid arthritis was 4-fold. The prevalence of pulmonary tuberculosis and disseminated tuberculosis was 59 (72.8%) and 22 (27.2%) respectively in rheumatoid disease patients. The incidence of tuberculosis with rheumatoid arthritis reduced from 47.6 to 28 per 100 000 with p<0.001. Conclusion: Our study found that pulmonary tuberculosis was more prevalent (72.7%) among adult tuberculosis patients with rheumatoid arthritis. Compared to general population, the tuberculosis incidence among rheumatoid arthritis patients was 4-fold. Keywords: Smear positive pulmonary tuberculosis, Rheumatoid arthritis, DMARDS

Screening for acquired latent tuberculosis in rheumatoid arthritis patients on tumor necrosis factor inhibition therapy in Southern California.

There are no studies assessing the development of latent tuberculosis infection (LTBI) in patients on tumor necrosis factor inhibitors (TNFα-I) in high TB prevalence areas of the USA. Our objective was to assess the rate of LTBI development in rheumatoid arthritis (RA) patients on TNFα-I therapies in San Bernardino and Riverside Counties of California, high TB prevalence areas in the US. Data were extracted from the electronic health record for 217 adult RA patients across three health centers from January 2010 to January 2017 who have had at least 1year of TNFα-I use and negative initial QuantiFERON Gold status. Demographics, TNFα-I type, duration of use, TB risk factors, QuantiFERON results, rates of re-screening, TB test seroconversion, and its association with drug use and other factors were assessed. Of the 217 patients, 115 (53%) received baseline and annual screening for LTBI. LTBI was diagnosed in 9.4% (10) of patients. Four patients were on infliximab, three on golimumab, two on adalimumab, and one on etanercept. Hispanic patients tended to have a greater than 200% increase in odds of seroconversion compared to non-Hispanic patients. Infliximab and golimumab were associated with a 92% and 400% increase in odds of seroconversion, respectively. The LTBI developed in 9.4% of the patients. This is higher than what is reported for previous US studies. Screening for LTBI in the US should take into consideration TB prevalence, ethnicity, drug type, and duration of use. For our local population and similar populations, annual screening should be practiced. Key Points • Although patients on TNFα inhibitor (TNFα-I) therapy are at high risk of latent tuberculosis infection (LTBI), few studies report the rate of LTBI in patients living in high prevalence areas of the US. • The rate of LTBI was 9.4% in patients on TNFα-I therapy in Southern California. The risk of seroconversion was higher in patients of Hispanic ethnicity and also higher for those on infliximab and golimumab compared to those on other TNFα-I therapies. • Screening guidelines for LTBI screening on TNFα-I should consider local TB prevalence, drugs used, duration of use and ethnicity for cost efficient, and optimal healthcare.

Safety of resuming biologic DMARDs in patients who develop tuberculosis after anti-TNF treatment

To estimate the incidence of tuberculosis (TB) in rheumatoid arthritis (RA) patients treated with tumor necrotizing factor inhibitor (TNFI) and evaluate the safety of resuming biologic disease-modifying anti-rheumatic drugs (DMARDs) in patients who developed TB after anti-TNF treatment. We conducted an inception cohort study of RA patients in the Korean Healthcare Claims Database who started TNFI as the first biologic DMARD between January 2009 and December 2013. The incidence rate (IR) of TB was estimated among total TNFI starters and a nested case-control analysis was performed to compare the characteristics of patients who developed TB and those did not. Patients diagnosed with relapsed TB after resuming biologic DMARDs were identified and their features were described. We included 4638 RA patients who started TNFI, contributing 8542 PYs of follow-up. The IR of TB in TNFI users was 1.10 (CI: 0.86-1.34) per 100 PYs. After the initial 6 months, the IR was highest at 1.56 (CI: 1.02-2.10) and decreased gradually over time. Among the 81 patients who developed TB, 30 patients (37.0%) resumed biologic DMARDs with a mean interval of 3.3 months after TB development. Two cases of TB were detected among 30 patients with an observational period of 45.7 PY. The IR of TB in RA patients who started TNFI was 1.10 per 100 PYs. This rate was highest during the first 6 months. Resumption of biologic DMARDs requires careful monitoring for TB relapse.

Risk of developing active tuberculosis in rheumatoid arthritis patients on adalimumab in Japan.

Nationwide study in Japan. To identify the clinical characteristics of and risk factors for tuberculosis (TB) in rheumatoid arthritis (RA) patients receiving adalimumab. A post hoc case-control study involving 7755 RA patients evaluated in an all-case post-marketing surveillance of adalimumab from 18 June 2008 to 20 January 2011 and spontaneous report of TB during adalimumab treatment. The analysis included 22 TB cases and 7733 non-TB controls. Despite the high frequency of extra-pulmonary TB (17/22, 77.3%), all 22 TB cases had pulmonary signs or symptoms. Of patients enrolled in all-case post-marketing surveillance, there were relatively high percentages of patients who had latent tuberculous infection (LTBI) at baseline. The percentage of patients who received prophylaxis was about six times higher in patients with LTBI than those without. Of those patients who received prophylaxis, none developed TB after treatment with adalimumab. Multivariate (non-matched and age-matched) and propensity score analyses identified age ⩾65 years (OR 4.59, 95%CI 1.52-13.89, P = 0.0070), moderate to severe RA (OR 4.61, 95%CI 1.07-20.00, P = 0.0408], past or current renal dysfunction (OR 4.65, 95%CI 1.47-14.71, P = 0.0089) and diabetes mellitus (OR 3.30, 95%CI 1.31-8.26, P = 0.0110) as potential risk factors for TB. Screening, prophylaxis and monitoring for TB are essential to ensure the safety of adalimumab treatment.

Tuberculosis chemoprophylaxis in rheumatoid arthritic patients receiving tumor necrosis factor inhibitors or conventional therapy

IntroductionPatients with rheumatoid arthritis (RA) have increased susceptibility to infection. The risk of acquiring infection including tuberculosis (TB) in RA may be increased in patients receiving any immuno-suppressive medication including anti-TNF therapy, which is used successfully for treating patients with rheumatoid arthritis. The aim of this work was to assess the risk of TB in RA patients on anti-TNF therapy compared to conventional disease modifying anti rheumatic drugs when screening for latent TB and TB chemoprophylaxis was applied. Patients and methodsThis study conducted on (235) RA patients indicated for either conventional therapy or anti-TNF therapy from 1-1-2010 to 1-10-2013. Assessment was done before RA treatment and included medical history, clinical examination, plain chest X-ray, HRCT chest QuantiFERON®-TB Gold in-tube (QFT-GIT) test and microbiologic investigations for tuberculosis when indicated. All patients with positive QFT-GIT received chemoprophylactic treatment for TB. ResultsThe studied rheumatoid arthritic patients were divided into two groups; group (A) included (105) RA patients on conventional disease modifying anti rheumatic drugs (DMARDs) with mean age (51±12) and group (B) included (130) RA patients on anti-TNF therapy with mean age (48±13). This study showed no significant increase of tuberculosis among patients on anti-TNF therapy (group B) compared to patients on (DMARDs) (group A). Chemo-prophylaxis in patients on anti-TNF therapy leads to prevention of reactivation of latent TB. ConclusionThere was no significant increased risk for tuberculosis among RA patients receiving anti-TNF therapy when screening and chemoprophylaxis was applied, so screening of RA patients before anti-TNF therapy for latent tuberculosis and TB chemoprophylaxis should be done.

AB0411 Tuberculosis Infection in Patients with Tumor Necrosis Factor Antagonists in South Korea; Retrospective Analysis Using by National Health Insurance Review and Assessment Service

BackgroundTumor necrosis factor-α (TNF-α) antagonists bring new hope for treating rheumatoid arthritis (RA) over the past decade. However, the subsequent increased risk of developing tuberculosis (TB) is one of the...

THU0413 Preventing Active Tuberculosis in Rheumatoid Arthritis Patients Receiving TNF Inhibitors: TB Screening at Baseline is not Enough

BackgroundTuberculosis (TB) is a major concern in patients treated with TNF inhibitors (TNFi), especially in countries with a high TB burden. Careful screening for active and latent TB is mandatory...

Risk of tuberculosis in rheumatoid arthritis patients on tumour necrosis factor-alpha inhibitor treatment in Taiwan

To quantify the incidence of tuberculosis (TB) in rheumatoid arthritis patients undergoing treatment with tumour necrosis factor-alpha inhibitors (TNFi). In a retrospective cohort study conducted using data from Taiwan's National Health Insurance claims databases, rheumatoid arthritis patients notified during the period 2006-2008 were recruited and classified based on types of TNFi treatment received. Active TB was the primary outcome. TB risk was estimated using Cox's proportional hazard model. The TB screening rate within 30 days of initiating treatment with TNFi was examined. Respectively 5079 and 829 patients were included in the non-TNFi and TNFi groups. Active TB rates were respectively 1411.3 and 679.5 events per 100,000 person-years in patients treated with adalimumab and etanercept. Significant TB risk was noted in patients treated with TNFi (aHR 4.87, 95%CI 2.14-11.06). No significant difference in active TB was observed between the TNFi subgroups (etanercept as reference, aHR 1.89, 95%CI 0.40-6.04). Only 8.7% (n = 9) of TNFi users underwent screening for TB before the first dose of TNFi. Patients on TNFi have a significantly greater risk of active TB than non-TNFi patients in the Taiwanese population. No difference in TB risk between the two available TNFi groups was noted. Screening for TB before initiating treatment with TNFi should be implemented.

THU0438 Peptidylarginine Deiminase Polymorphisms Associated with Susceptibility to Tuberculosis

BackgroundAnti–cyclic citrullinated peptide antibodies (as a serologic marker of RA) bind to citrulline residue which is now considered to play a pivotal role in various human diseases such as multiple...

THU0437 Disease Modifying Effect of Tuberculosis on Coexistent Systemic Vasculitis in Rheumatoid Arthritis – A Retrospective Clinicopathologic Study of 234 Autopsy Patients

BackgroundCoexisting associated diseases modify the features of rheumatoid arthritis (RA) by presenting atypical clinical manifestations and vice versa (1). The atypical signs and symptoms may lead to incorrect diagnosis or...

A Case of Rituximab Use in Rheumatoid Arthritis Following Anti-TNF-Associated Tuberculosis

Rituximab has been shown to be effective in rheumatoid arthritis (RA) and is recommended for patients exhibiting an inadequate response to tumor necrosis factor (TNF) inhibitors. To date, there have been no reports of tuberculosis in RA patients treated with rituximab. We report the use of rituximab in a TNF inhibitor-refractory RA patient who had developed tuberculosis. A 52-year-old man with RA had been treated with adalimumab for 3 months, but failed to respond well to the treatment. He reported fever, coughing, sputum, and weight loss. He was diagnosed with pulmonary tuberculosis and started anti-tuberculosis medication. His arthritis was not controlled for despite increasing the dose of prednisolone. He was treated with rituximab without serious adverse effects. Sixteen weeks later, he demonstrated improvement with both arthritis and tuberculosis.

Biphasic emergence of active tuberculosis in rheumatoid arthritis patients receiving TNFα inhibitors: the utility of IFNγ assay

ObjectivesThe risk of active tuberculosis increases in rheumatoid arthritis (RA) patients receiving antitumour necrosis factor alpha (TNFα) therapy. Longitudinal data concerning serial interferon γ (IFNγ) assays for detecting tuberculosis have...

Incidence of tuberculosis in patients with rheumatoid arthritis. A systematic literature review

Objectives To determine the incidence and risk of tuberculosis in rheumatoid arthritis (RA) patients exposed or unexposed to TNFα antagonists, the impact of recommendations about managing latent tuberculosis, the time to diagnosis of active tuberculosis, and the proportion of extrapulmonary forms. Methods Systematic review of articles retrieved using Medline. From each article, we abstracted the incidence and risk of tuberculosis in RA patients exposed or unexposed to TNFα antagonists, the duration of TNFα antagonist exposure at the diagnosis of tuberculosis, and the distribution of the tuberculosis foci. Results We selected 14 articles. The risk of tuberculosis was increased 2- to 10-fold in RA patients unexposed to TNFα antagonists and 2- to 4-fold in those exposed to TNFα antagonists, compared to the general population. The incidence of tuberculosis in TNFα antagonist-treated patients varied across studies (9.3 to 449/100,000) according to the country, observation period, and TNFα antagonist used. The risk was greater with monoclonal antibodies than with the soluble receptor. Official recommendations have decreased the risk of tuberculosis in TNFα antagonist-treated patients. Over half the cases of active tuberculosis were diagnosed during the first treatment year. Among TNFα antagonist-treated patients with tuberculosis, 60% had extrapulmonary lesions. Disseminated tuberculosis was more common with monoclonal antibodies. Conclusions The risk of tuberculosis is increased during TNFα antagonist therapy, and the increase is larger with the monoclonal antibodies than with the soluble receptor. Tuberculosis during TNFα antagonist therapy is a rare event that occurs early after treatment initiation. Extrapulmonary involvement is common and potentially severe. Therefore, clinicians should direct careful attention to the risk of tuberculosis associated with TNFα antagonist therapy.

Cost Effectiveness of Interferon-Gamma Release Assay for Tuberculosis Screening of Rheumatoid Arthritis Patients prior to Initiation of Tumor Necrosis Factor-α Antagonist Therapy

The prevalence of tuberculosis (TB) in rheumatoid arthritis (RA) patients is higher than that in the general population, and RA patients are considered a high-risk group. Currently, TB screening of RA patients receiving immunosuppressive therapy such as tumor necrosis factor-α (TNFα) antagonists is performed by the tuberculin skin test (TST) in Japan. Interferon-gamma release assays (QuantiFERON®-TB Gold In-Tube [QFT] and T-SPOT.TB®) are new alternatives to the TST to diagnose latent TB infection (LTBI) and active TB, and offer higher specificity and no cross-reactivity with Bacillus Calmette-Guérin (BCG) vaccine. We evaluated the cost effectiveness of QFT versus TST in non-BCG-vaccinated and BCG-vaccinated RA patients. We constructed a Markov model to evaluate the cost effectiveness of QFT and TST. The target population is a hypothetical cohort of 1000 RA patients, using a societal perspective and the lifetime horizon. All costs and clinical benefits were discounted at a fixed annual rate of 3%. In base-case analysis, the QFT strategy was the most cost effective ($US1044.52; 23.03499 quality-adjusted life-years [QALYs]) compared with the TST strategy for non-BCG-vaccinated RA patients ($US1824.61; 22.98153 QALYs) and for BCG-vaccinated RA patients ($US2096.34; 22.98153 QALYs) [year 2009 values]. The incidence of TB in RA patients with TNFα antagonist therapy influenced the cost effectiveness. When the incidence of TB in RA patients with TNFα antagonist therapy is under 0.00066, the TST strategy is more cost effective than the QFT strategy. QFT screening is more effective and less costly than the TST for both BCG-vaccinated and non-BCG-vaccinated RA patients prior to TNFα antagonist therapy in Japan. These findings may be applicable to other countries when choosing optimal LTBI screening of RA patients.

Rheumatoid arthritis, its treatments, and the risk of tuberculosis in Quebec, Canada

To determine the risk of tuberculosis (TB) among a cohort of patients with rheumatoid arthritis (RA) in Quebec and assess whether this risk is associated with exposure to nonbiologic disease-modifying antirheumatic drugs (DMARDs). We studied a cohort of patients with RA identified from the Quebec provincial physician billing and hospitalization databases for 1980-2003. TB incidence rates were determined for the period 1992-2003 and compared with the general population, standardized for age and sex using the standardized incidence ratio (SIR). Conditional logistic regression was used in a nested case-control analysis to estimate the rate ratio (RR) of TB related to nonbiologic DMARD exposure during the year before the index date. Of the 24,282 patients with RA in the cohort, 50 cases of TB were identified. The standardized incidence rate was 45.8 cases per 100,000 person-years compared with 4.2 cases per 100,000 person-years in the general population of Quebec (SIR 10.9, 95% confidence interval [95% CI] 7.9-15.0). The adjusted RR of TB was 2.4 (95% CI 1.1-5.4) with corticosteroid use and 3.0 (95% CI 1.6-5.8) with nonbiologic DMARD use. The age- and sex-standardized incidence rate of TB in RA patients is 10 times that of the general population. At least some of this risk may be related to nonbiologic DMARD and corticosteroid therapies. Our data support the role of TB screening before initiation of any immunosuppressive therapy.

Screening of tuberculosis by interferon-γ assay before biologic therapy for rheumatoid arthritis

Infection with Mycobacterium tuberculosis (M. tuberculosis) is a critical complication in anti-TNF therapies. In 141 BCG vaccinated healthy individuals and 71 rheumatoid arthritis (RA) patients as screening before anti-TNF therapies, M. tuberculosis specific immune responses were evaluated by tuberculin skin test (TST) and enzyme-linked immunospot assay (ELISPOT), which detected antigen specific IFN-gamma secreting cells in peripheral blood mononuclear cells simulated with either purified protein derivative (PPD), early secretory antigen target 6 (ESAT-6) or culture filtrate protein 10 (CFP-10). Induration over 5 mm in TST was found in 87.9% of controls and 21.4% of RA patients. Erythema size in TST was significantly suppressed in RA patients, especially those receiving prednisolone (PSL), whereas the PPD specific IFN-gamma secretion was less attenuated. Significant responses to either ESAT-6 or CFP-10 in ELISPOT were detected in 14.1% of RA patients including those having positive TST, while the ELISPOT assay was negative in all healthy individuals and 73.3% of RA patients having positive TST. Of ELISPOT positive RA patients, mean dosage of PSL was 4.58 mg and 1.25 mg in TST negative and positive patients, respectively. Thus, ELISPOT is useful for screening of tuberculosis in RA patients, even in those receiving corticosteroids.

Guidelines for Prevention of Tuberculosis in Patients with Rheumatoid Arthritis Treated with TNF-alpha Blockers

Introduction of tumor necrosis factor (TNF) inhibitor for the treatment of rheumatoid arthritis (RA) induces not only significant improvement of symptoms and signs of RA but also substantial inhibition of progressive joint damage. Such therapeutic efficacies of TNF inhibitor have led to a paradigm shift in the treatment of RA. In spite of its dramatic effect against RA, it is now well established that the use of TNF inhibitor significantly increases the risk of tuberculosis in patients with RA. Therefore some countries have presented guidelines in the use of TNF inhibitors for rheumatoid arthritis to reduce the risk of tuberculosis. Korea Food and Drug Association (KFDA) have also provided guidelines for treating latent tuberculosis when using TNF inhibitors. In this article, we reviewed the general epidemiology of tuberculosis and incidence rates of tuberculosis in RA patients and those of RA patients treated with TNF inhibitors. We also introduced methods for the diagnosis of latent tuberculosis, and various guidelines published in different countries in managing tuberculosis in RA patients who were to be treated with TNF inhibitors. Finally, we suggest requirement of more appropriate guidelines for Korean RA patients who are candidates for treatment with TNF-inhibitors.

Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden

Because treatment with tumor necrosis factor (TNF) antagonists may increase the risk of tuberculosis (TB), and because knowledge of the risk of TB in rheumatoid arthritis (RA) not treated with biologics is scarce and of uncertain generalizability to low-risk populations, this study sought to determine the risk of TB among Swedish patients with RA. Using data from Swedish nationwide and population-based registers and data from an ongoing monitoring program of TNF antagonists, the relative risks of TB in patients with RA (versus the general population) and of TB associated with TNF antagonists (versus RA patients not treated with biologics) were determined by comparing the incidence of hospitalization for TB in 3 RA cohorts and 2 general population cohorts from 1999 to 2001. We also reviewed the characteristics of all reported cases of TB in RA patients treated with TNF antagonists in Sweden and calculated the incidence of TB per type of TNF antagonist between 1999 and 2004. During 1999-2001, RA patients who were not treated with TNF antagonists were at increased risk of TB versus the general population (relative risk 2.0, 95% confidence interval [95% CI] 1.2-3.4). RA patients treated with TNF antagonists had a 4-fold increased risk of TB (relative risk 4.0, 95% CI 1.3-12) versus RA patients not treated with TNF antagonists. The reported TB cases during 1999-2004 in RA patients exposed to TNF antagonists (9 infliximab, 4 etanercept, 2 both) were predominantly pulmonary. TB occurred up to 3 years following the start of treatment. Irrespective of whether TNF antagonists are administered, Swedish patients with RA are at increased risk of TB. During 1999-2001, TNF antagonists were associated with an increased risk of TB, up to 4-fold in magnitude. This increased risk may persist over time during treatment and is related to both infliximab and etanercept.

Prevalence and clinical characteristics of tuberculosis in rheumatoid arthritis patients

Patients with rheumatoid arthritis (RA) have been shown to have an increased susceptibility to the development of infections [1, 2]. The exact causes of this increased risk are unknown, but may be related to immunologic disturbances associated with the disease or to the immunosuppressive effects of agents used in its treatment [3, 4]. Recently, the question of whether patients with RA are at increased risk of developing tuberculosis compared with the general population has gained interest in light of reports of serious cases in patients receiving biologic therapies for the disease [5, 6]. Mycobacterium infection is an important cause of morbidity and mortality in patients with RA, especially in prevalent areas [7, 8]. Tuberculosis infection in RA has been reported with an incidence rate of 2.3/1000 patient years, which is higher than in the general population [7]. According to a national study, the prevalence of active tuberculosis in Morocco is estimated to be 160–180/100,000 patients. The aim of this report was to assess the prevalence and the clinical features of tuberculosis infection in RA patients living in Morocco.

Clinical characteristics of Mycobacterium tuberculosis infection among rheumatoid arthritis patients

To evaluate the clinical characteristics of Mycobacterium tuberculosis infection in rheumatoid arthritis (RA) patients, we examined the clinical manifestations and radiography/computed tomography (CT) findings in RA patients with tuberculosis (RA+/TB+). A total of 1121 tuberculosis patients were admitted to our hospital from 1995 to 2003, with the RA patients among them comprising 1.8% (20 cases; 9 men and 11 women). This is approximately three times as high as the prevalence of RA in the entire population in Japan. In addition, the RA+/TB+ patients were older and had a longer history of RA than the 140 outpatients in our RA clinic who did not have tuberculosis (RA+/TB−). Half of the RA+/TB+ patients had no symptoms (e.g., cough, sputum, pyrexia), and their tuber-culosis was detected accidentally by radiography/CT. The positive rates of the bacilli in the smear and culture of the sputum from the RA+/TB+ patients were lower than those from 143 patients randomly selected from among 1091 tuberculosis patients without any collagen disease including RA (RA−/TB+). The RA+/TB+ patients had a higher incidence of extrapulmonary tuberculosis (30%), including four cases (20%) of miliary tuberculosis, an incidence seven times higher than among the general population of tuberculosis patients. Among 14 cases of pulmonary tuberculosis patients with RA, bilateral lesions and noncavitary lesions were found in 71.4% and 64.3%, respectively, which tended to be a higher incidence than in the RA−/TB+ patients. The mortality rate and sputum conversion time of the RA+/TB+ patients were no different from those of the RA−/TB+ patients. The prevalence of tuberculosis in RA patients is expected to increase after introduction of anticytokine therapy in Japan, and careful observation should be done to avoid this complication in RA patients.