Incidence of tuberculosis in Korean patients with rheumatoid arthritis (RA): effects of RA itself and of tumor necrosis factor blockers

OBJECTIVE: To elucidate the incidence rate and relative risk of tuberculosis (TB) in patients with rheumatoid arthritis (RA) and in patients with RA treated with tumor-necrosis-factor (TNF) blockers in Korea. METHODS: Using data from the Korean National Tuberculosis Association (KNTA) as a control and data from a single-center cohort of patients with RA, we conducted an evaluation of 1285 patients with RA not exposed to TNF blockers and reviewed medical records of 90 and 103 patients with RA treated with infliximab and etanercept, respectively, between 2001 and 2005. RESULTS: The mean incidence rate of TB, reported by the KNTA, was 67.2 per 100,000 person years (PY) from 2001 to 2004. In the TNF-blocker-na?ve RA cohort, 9 cases of TB developed during 3497 PY of followup (257 per 100,000). In the infliximab-treated RA group, 2 cases of TB developed during 78.17 PY of followup (2558 per 100,000 PY), and there was no case of TB during 73.67 PY of followup in the etanercept-treated RA group. The risk of TB was higher in RA patients not treated with TNF blockers (sex- and age-adjusted risk ratio 8.9; 95% confidence interval 4.6-17.2), and in those treated with infliximab (sex- and age-adjusted risk ratio, 30.1; 95% confidence interval, 7.4-122.3) compared with the general Korean population. CONCLUSION: The risk of TB infection is 8.9-fold higher in Korean patients with RA and 30.1-fold higher in RA patients treated with infliximab, compared with the general Korean population.     

Infections in patients with rheumatoid arthritis treated with biologic agents

OBJECTIVE: To estimate the incidence rates of serious and nonserious infections in patients with rheumatoid arthritis (RA) who start treatment with a biologic agent, and to compare these rates with those in patients with RA who receive conventional treatment. METHODS: Patients enrolled in the German biologics register between May 2001 and September 2003 were included. Treating rheumatologists assessed adverse events and serious adverse events. All adverse events and serious adverse events experienced within 12 months after study entry were analyzed. Propensity score methods were applied to estimate which part of a rate increase was likely to be attributable to differences in patient characteristics. RESULTS: Data were available for 512 patients receiving etanercept, 346 patients receiving infliximab, 70 patients receiving anakinra, and 601 control patients treated with disease-modifying antirheumatic drugs. The total number of adverse events per 100 patient-years was 22.6 (95% confidence interval [95% CI] 18.7-27.2) among patients receiving etanercept, 28.3 (95% CI 23.1-34.7) among patients receiving infliximab, and 6.8 (95% CI 5.0-9.4) among controls (P < 0.0001). Significant differences in the rate of serious adverse events were also observed. For patients receiving etanercept, those receiving infliximab, and controls, the total numbers of serious adverse events per 100 patient-years were 6.4 (95% CI 4.5-9.1), 6.2 (95% CI 4.0-9.5), and 2.3 (95% CI 1.3-3.9), respectively (P = 0.0016). After adjusting for differences in the case patient mix, the relative risks of serious adverse events were 2.2 (95% CI 0.9-5.4) for patients receiving etanercept and 2.1 (95% CI 0.8-5.5) for patients receiving infliximab, compared with controls. CONCLUSION: Patients treated with biologic agents have a higher a priori risk of infection. However, our data suggest that this risk is increased by treatment with tumor necrosis factor inhibitors.     

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

Objective

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).

Methods

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.

Results

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.

Conclusion

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.     

Risk of tuberculosis in patients treated with tumor necrosis factor antagonists due to incomplete prevention of reactivation of latent infection

OBJECTIVE: To evaluate the causes of new cases of active tuberculosis (ATB) in patients treated with tumor necrosis factor (TNF) antagonists included in the national registry BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Espa?ola de Reumatología) after the dissemination of recommendations to prevent reactivation of latent tuberculosis infection (LTBI). METHODS: Incidence rate of ATB per 100,000 patient-years and 95% confidence intervals (95% CIs) were calculated in patients entering BIOBADASER after March 2002 and were stratified by compliance with recommendations (complete or incomplete). ATB rates in BIOBADASER were compared with the background rate and the rate in the rheumatoid arthritis cohort EMECAR (Estudio de la Morbilidad y Expresión Clínica de la Artritis Reumatoide) not treated with TNF antagonists. In addition, rates of ATB among patients treated with adalimumab, etanercept, and infliximab were estimated and compared only for treatments started after September 2003, when all 3 drugs became fully available. RESULTS: Following March 2002, a total of 5,198 patients treated with a TNF antagonist were registered in BIOBADASER. Fifteen ATB cases were noted (rate 172 per 100,000 patient-years, 95% CI 103-285). Recommendations were fully followed in 2,655 treatments. The probability of developing ATB was 7 times higher when recommendations were not followed (incidence rate ratio 7.09, 95% CI 1.60-64.69). Two-step tuberculosis skin test for LTBI was the major failure in complying with recommendations. CONCLUSION: New cases of ATB still occur in patients treated with all available TNF antagonists due to lack of compliance with recommendations to prevent reactivation of LTBI. Continuous evaluation of recommendations is required to improve clinical practice.     

Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists

OBJECTIVE: To investigate the impact of official recommendations regarding the management of latent tuberculosis (TB) infection on the rate of active TB in patients receiving treatment with tumor necrosis factor (TNF) antagonists. METHODS: Data on active TB rates and on screening and treatment of latent TB infection were extracted from the BIOBADASER (Spanish Society of Rheumatology Database on Biologic Products), a registry of patients with rheumatic conditions treated with TNF antagonists. The rates of active TB among the BIOBADASER patients were compared with those in the background Spanish population, and BIOBADASER patients with rheumatoid arthritis (RA) were compared with a cohort of RA patients from the EMECAR (Morbidity and Clinical Expression of Rheumatoid Arthritis) study who were not treated with TNF antagonists and were followed up for 5 years. RESULTS: Active TB developed in 34 patients, of whom 32 started taking TNF antagonists prior to the official recommendations on latent TB infection (pre-OR) and 2 began treatment after the recommendations were issued (post-OR). All cases of TB occurred during treatment with infliximab, and 28 of these patients had RA. Pre-OR, the active TB rate in BIOBADASER patients was 20.9-fold higher than in the background Spanish population, while RA patients in the BIOBADASER had rates 22.6- and 6.2-fold higher than the background and EMECAR populations, respectively. Post-OR, 324 patients with a tuberculin skin test result > or =5 mm and/or chest radiograph findings suggestive of past TB were treated for 9 months with isoniazid (INH). Post-OR, active TB rates among the BIOBADASER patients decreased by 78% (incidence risk ratio [IRR] 0.22, 95% confidence interval [95% CI] 0.03-0.88; P = 0.008), while among RA patients in the BIOBADASER, the rate dropped by 83% and reached the EMECAR rate (IRR 1.0, 95% CI 0.02-8.2). There were no INH treatment-related hospitalizations or deaths. CONCLUSION: Strategies to treat latent TB infection that are tailored to the at-risk population can effectively and safely lessen the likelihood of active TB in patients treated with TNF antagonists.     

Rates and predictors of herpes zoster in patients with rheumatoid arthritis and non-inflammatory musculoskeletal disorders

OBJECTIVES: Herpes zoster (HZ) is a common disorder that causes substantial pain and morbidity. We examined its rate and predictors in rheumatoid arthritis (RA) and non-inflammatory musculoskeletal (MSK) disorders to determine if HZ was increased in RA and whether treatment contributed to the risk of HZ. METHODS: After excluding patients witzh prior HZ, we assessed 10 614 RA and 1721 MSK patients by semi-annual questionnaires during 33 825 patient-years of follow-up. Predictors of HZ were determined by Cox regression and expressed as hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: The annualized incidence rate per 1000 patient-years was 13.2 (95% CI 11.9-14.5) in RA and 14.6 (95% CI 11.2-18.1) in MSK, and did not differ significantly after adjustment for age and sex. HZ was predicted by impaired functional status, as measured by the Health Assessment Questionnaire (HAQ), [HR 1.3 (95% CI 1.1-1.5)] and by the use of COX-2-specific non-steroidal anti-inflammatory drugs (NSAIDs) [HR 1.3 (95% CI 1.1-1.6)] in RA and MSK. In multivariable analyses in patients with RA, cyclophosphamide HR 4.2 (95% CI 1.6-11.5), azathioprine HR 2.0 (1.2-3.3), prednisone HR 1.5 (1.2-1.8), leflunomide HR 1.4 (1.1-1.8) and COX-2 NSAIDs HR 1.3 (95% CI 1.1-1.6) were significant predictors of HZ. CONCLUSION: The incidence of HZ is increased in RA and MSK compared with population-based rates. However, the rate of HZ in RA is not increased compared with MSK. After adjustment for severity, various treatments, but not methotrexate or biologics, were risk factors for HZ.     

Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report

OBJECTIVE: The long-term safety of therapeutic agents that neutralize tumor necrosis factor (TNF) is uncertain. Recent evidence based on spontaneous reporting shows an association with active tuberculosis (TB). We undertook this study to determine and describe the long-term safety of 2 of these agents, infliximab and etanercept, in rheumatic diseases based on a national active-surveillance system following the commercialization of the drugs. METHODS: We analyzed the safety data actively collected in the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Espa?ola de Reumatología) database, which was launched in February 2000 by the Spanish Society of Rheumatology. For the estimation of TB risk, the annual incidence rate in patients treated with these agents was compared with the background rate and with the rate in a cohort of patients with rheumatoid arthritis (RA) assembled before the era of anti-TNF treatment. RESULTS: Seventy-one participating centers sent data on 1,578 treatments with infliximab (86%) or etanercept (14%) in 1,540 patients. Drug survival rates (reported as the cumulative percentage of patients still receiving medication) for infliximab and etanercept pooled together were 85% and 81% at 1 year and 2 years, respectively. Instances of discontinuation were essentially due to adverse events. Seventeen cases of TB were found in patients treated with infliximab. The estimated incidence of TB associated with infliximab in RA patients was 1,893 per 100,000 in the year 2000 and 1,113 per 100,000 in the year 2001. These findings represent a significant increased risk compared with background rates. In the first 5 months of 2002, after official guidelines were established for TB prevention in patients treated with biologics, only 1 new TB case was registered (in January). CONCLUSION: Therapy with infliximab is associated with an increased risk of active TB. Proper measures are needed to prevent and manage this adverse event.     

Differences in the incidence of flares or new onset of inflammatory bowel diseases in patients with ankylosing spondylitis exposed to therapy with anti-tumor necrosis factor alpha agents

OBJECTIVE: Ankylosing spondylitis (AS) and inflammatory bowel disease (IBD) are clinically and pathologically linked. Anti-tumor necrosis factor (anti-TNF) agents are efficacious in treating AS, but not all are equally effective in treating IBD (Crohn's disease [CD] and ulcerative colitis [UC]). The purpose our study was to analyze the incidence of flares and new onset of IBD in patients with AS treated with anti-TNF agents. METHODS: Data from 9 trials, 7 placebo-controlled trials and 2 open studies, were analyzed. RESULTS: Data were available on 419 AS patients exposed to etanercept (625 patient-years), 366 exposed to infliximab (618 patient-years), 295 exposed to adalimumab (132 patient-years), and 434 placebo patients (150 patient-years). A history of IBD was reported in 76 of 1,130 patients (6.7%). There were 2 reports of IBD while receiving placebo (1.3 per 100 patient-years), 1 while receiving infliximab, and 3 while receiving adalimumab. Among the 14 IBD cases receiving etanercept (2.2 per 100 patient-years) there were 8 CD and 6 UC cases, significantly different from infliximab (P = 0.01) but not from placebo. Patients with a history of IBD had an IBD flare odds ratio of 18.0 (95% confidence interval [95% CI] 2-154) while taking etanercept and 4.2 (95% CI 0.4-44) while taking adalimumab, in comparison with infliximab. The incidence rates of new onset of IBD showed no significant difference between etanercept (0.8 per 100 patient-years) and placebo (0.5 per 100 patient-years). CONCLUSION: New onset and flare of IBD are infrequent events in AS patients receiving anti-TNF therapy. Infliximab (but not etanercept) largely prevents IBD activity. More data are required for adalimumab. The incidence of new onset of IBD was statistically not different from placebo for all anti-TNF agents.     

Increased risk of tuberculosis in patients with rheumatoid arthritis

OBJECTIVE: To quantify the risk of tuberculosis (TB) in an unselected sample of patients with rheumatoid arthritis (RA) compared to the risk in the general population. METHODS: The incidence of TB in the general population of Spain was obtained from the National Network of Epidemiological Surveillance reports. The incidence of TB was ascertained from a cohort of 788 patients with RA selected randomly from the registries of 34 participating centers throughout Spain. A patient was considered a TB case only if information about disease symptoms, microorganism identification, and TB treatment were confirmed in the clinical records. The relative risk of TB in RA was calculated by dividing the standardized mean incidence of TB from 1990 to 2000 in the RA cohort by the mean incidence of TB in Spain during the same years. RESULTS: The mean incidence of TB in the general population of Spain from 1990 to 2000 was 23 cases per 100,000. Seven cases of TB were identified in the RA cohort, yielding a mean annual incidence (1990-2000) of 134/100,000 patients. The incidence risk ratio of pulmonary TB in patients with RA compared to the general population is 3.68 (95% CI 2.36-5.92). CONCLUSION: We found a 4-fold increased risk of TB infection in patients diagnosed with RA. These results might help to interpret the magnitude of the problem attributable to the introduction of new therapies in RA.     

Lymphoma in rheumatoid arthritis: the effect of methotrexate and anti-tumor necrosis factor therapy in 18,572 patients

OBJECTIVE: The risk of lymphoma is increased in patients with rheumatoid arthritis (RA), and spontaneous reporting suggests that methotrexate (MTX) and anti-tumor necrosis factor (anti-TNF) therapy might be associated independently with an increased risk of lymphoma. However, data from clinical trials and clinical practice do not provide sufficient evidence concerning these issues because of small sample sizes and selected study populations. The objective of this study was to determine the rate of and standardized incidence ratio (SIR) for lymphoma in patients with RA and in RA patient subsets by treatment group. Additionally, we sought to determine predictors of lymphoma in RA. METHODS: We prospectively studied 18,572 patients with RA who were enrolled in the National Data Bank for Rheumatic Diseases (NDB). Patients were surveyed biannually, and potential lymphoma cases received detailed followup. The SEER (Survey, Epidemiology, and End Results) cancer data resource was used to derive the expected number of cases of lymphoma in a cohort that was comparable in age and sex with the RA cohort. RESULTS: The overall SIR for lymphoma was 1.9 (95% confidence interval [95% CI] 1.3-2.7). The SIR for biologic use was 2.9 (95% CI 1.7-4.9) and for the use of infliximab (with or without etanercept) was 2.6 (95% CI 1.4-4.5). For etanercept, with or without infliximab, the SIR was 3.8 (95% CI 1.9-7.5). The SIR for MTX was 1.7 (95% CI 0.9-3.2), and was 1.0 (95% CI 0.4-2.5) for those not receiving MTX or biologics. Lymphoma was associated with increasing age, male sex, and education. CONCLUSION: Lymphomas are increased in RA. Although the SIR is greatest for anti-TNF therapies, differences between therapies are slight, and confidence intervals for treatment groups overlap. The increased lymphoma rates observed with anti-TNF therapy may reflect channeling bias, whereby patients with the highest risk of lymphoma preferentially receive anti-TNF therapy. Current data are insufficient to establish a causal relationship between RA treatments and the development of lymphoma.     

Comparison of tuberculosis incidence in ankylosing spondylitis and rheumatoid arthritis during tumor necrosis factor inhibitor treatment in an intermediate burden area

Clinical characteristics of antitumor necrosis factor (TNF) agents-related tuberculosis (TB) in ankylosing spondylitis (AS) are not well described. The aim was to compare the incidences and the characteristics of TB in AS and rheumatoid arthritis (RA) during TNF inhibitor treatment. AS (n?=?1,322) and RA (n?=?3,154) patients who received medical care between January 2001 and August 2011 were enrolled. The incidence of TB in patients treated, or not, with TNF inhibitors and the clinical features associated with TB were explored. Seven patients with AS and seven with RA developed TB while receiving TNF inhibitor therapy, resulting in an incidence rate of 600.2/100,000 person-years (PYs) (95 % confidence interval (CI), 241.3–1236.3) for those with AS and 771.6/100,000 PYs (95 % CI, 310.2–1589.9) for those with RA. Incidence rate ratios for TNF inhibitor-treated vs. untreated patients were 4.87 for AS (95 % CI, 1.50–15.39; p?p?p?=?0.002). Extrapulmonary TB was predominant at 85.7 % during TNF inhibitor treatment. Three (42.8 %) of the AS patients, but none of the RA patients, developed TB with concomitant isoniazid. All AS patients recovered from TB whereas two of seven RA patients died. Treatment with TNF inhibitors significantly increases the risk of extrapulmonary TB in AS. Symptoms of infection should warrant clinicians to evaluate for TB during TNF inhibitor therapy in AS patients.     

Risk of tuberculosis is higher with anti–tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: The three‐year prospective french research axed on tolerance of biotherapies registry

Objective

Tuberculosis (TB) is associated with anti–tumor necrosis factor (anti‐TNF) monoclonal antibody (mAb) therapy, but whether this association is drug‐specific remains a concern. Our objective was to describe cases of TB associated with anti‐TNF mAb therapy, identify risk factors, and estimate the incidence.

Methods

We conducted an incidence study and a case–control analysis to investigate the risk of newly diagnosed TB associated with the use of anti‐TNF agents. As part of the French Research Axed on Tolerance of Biotherapies (RATIO) registry, for 3 years we collected cases of TB among French patients receiving anti‐TNF mAb therapy for any indication; for each case, 2 patients treated with anti‐TNF agents served as control subjects.

Results

We collected 69 cases of TB in patients treated for rheumatoid arthritis (n = 40), spondylarthritides (n = 18), inflammatory colitis (n = 9), psoriasis (n = 1) and Behçet's disease (n = 1) with infliximab (n = 36), adalimumab (n = 28), and etanercept (n = 5). None of the patients had received correct chemoprophylactic treatment. The sex‐ and age‐adjusted incidence rate of TB was 116.7 per 100,000 patient‐years. The standardized incidence ratio (SIR) was 12.2 (95% confidence interval [95% CI] 9.7–15.5) and was higher for therapy with infliximab and adalimumab than for therapy with etanercept (SIR 18.6 [95% CI 13.4–25.8] and SIR 29.3 [95% CI 20.3–42.4] versus SIR 1.8 [95% CI 0.7–4.3], respectively). In the case–control analysis, exposure to infliximab or adalimumab versus etanercept was an independent risk factor for TB (odds ratio [OR] 13.3 [95% CI 2.6–69.0] and OR 17.1 [95% CI 3.6–80.6], respectively). Other risk factors were age, the first year of anti‐TNF mAb treatment, and being born in an endemic area.

Conclusion

The risk of TB is higher for patients receiving anti‐TNF mAb therapy than for those receiving soluble TNF receptor therapy. The increased risk with early anti‐TNF treatment and the absence of correct chemoprophylactic treatment favor the reactivation of latent TB.

     

Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: A multicenter active‐surveillance report

Objective

The long‐term safety of therapeutic agents that neutralize tumor necrosis factor (TNF) is uncertain. Recent evidence based on spontaneous reporting shows an association with active tuberculosis (TB). We undertook this study to determine and describe the long‐term safety of 2 of these agents, infliximab and etanercept, in rheumatic diseases based on a national active‐surveillance system following the commercialization of the drugs.

Methods

We analyzed the safety data actively collected in the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) database, which was launched in February 2000 by the Spanish Society of Rheumatology. For the estimation of TB risk, the annual incidence rate in patients treated with these agents was compared with the background rate and with the rate in a cohort of patients with rheumatoid arthritis (RA) assembled before the era of anti‐TNF treatment.

Results

Seventy‐one participating centers sent data on 1,578 treatments with infliximab (86%) or etanercept (14%) in 1,540 patients. Drug survival rates (reported as the cumulative percentage of patients still receiving medication) for infliximab and etanercept pooled together were 85% and 81% at 1 year and 2 years, respectively. Instances of discontinuation were essentially due to adverse events. Seventeen cases of TB were found in patients treated with infliximab. The estimated incidence of TB associated with infliximab in RA patients was 1,893 per 100,000 in the year 2000 and 1,113 per 100,000 in the year 2001. These findings represent a significant increased risk compared with background rates. In the first 5 months of 2002, after official guidelines were established for TB prevention in patients treated with biologics, only 1 new TB case was registered (in January).

Conclusion

Therapy with infliximab is associated with an increased risk of active TB. Proper measures are needed to prevent and manage this adverse event.

     

The effect of methotrexate and anti-tumor necrosis factor therapy on the risk of lymphoma in rheumatoid arthritis in 19,562 patients during 89,710 person-years of observation

OBJECTIVE: To ascertain the relationship between anti-tumor necrosis factor (anti-TNF) therapy, methotrexate (MTX), and the risk of lymphoma in patients with rheumatoid arthritis (RA). This report updates our previous report during 29,314 person-years of followup. METHODS: Participants in the National Data Bank for Rheumatic Diseases (NDB) longitudinal study of long-term outcomes of RA completed semiannual questionnaires from 1998 through 2005, during 89,710 person-years of followup. Lymphoma reports were validated by medical records. The association between lymphoma and treatment was investigated using conditional logistic regression, adjusted for severity and demographic covariates. RESULTS: Of the 19,591 participants, 55.3% received biologic agents and 68.0% received MTX while enrolled in the NDB. The lymphoma incidence rate was 105.9 (95% confidence interval [95% CI] 86.6-129.5) per 100,000 person-years of exposure. Compared with the SEER (Surveillance, Epidemiology, and End-Results) lymphoma database, the standardized incidence ratio was 1.8 (95% CI 1.5-2.2). The odds ratio (OR) for lymphoma in patients who received anti-TNF therapy compared with patients who did not receive anti-TNF therapy was 1.0 (95% CI 0.6-1.8 [P = 0.875]). The OR for lymphoma in patients who received anti-TNF plus MTX therapy compared with patients who received MTX treatment alone was 1.1 (95% CI 0.6-2.0 [P = 0.710]). Infliximab and etanercept considered individually also were not associated with a risk of lymphoma. CONCLUSION: In a study of lymphoma in 19,591 RA patients over 89,710 person-years of followup, which included exposure to anti-TNF therapy in 10,815 patients, we did not observe evidence for an increase in the incidence of lymphoma among patients who received anti-TNF therapy.     

High risk of tuberculosis in systemic lupus erythematosus?

The incidence and severity of tuberculosis (TB) in patients with systemic lupus erythematosus (SLE) varies greatly among different series. In addition, prospective data are scarce. The aim of this study is to analyse the frequency and severity of TB in our cohort of lupus patients. We analysed data from a prospective database of a single center cohort of 232 patients with SLE (ACR criteria). Prophylaxis with isoniazid was not regularly administered. We identified all cases of TB diagnosed during 10 years (January 1994 to December 2003). The following variables were analysed: annual incidence of TB, location of infection and response to therapy. Data from published series reporting on the incidence of TB among SLE patients were extracted. Three patients (1.3%) suffered clinically manifest TB in 1603 patient-years of follow-up, resulting in an incidence of 187 cases/100,000 patient-years (95% CI 39-547). The pooled annual incidence of TB infection in our area during this period was 30/100,000 individuals. We recorded two cases of pulmonary TB and one case of tuberculous pleurisy. All patients had good response to therapy. The annual incidence of TB among SLE patients in other series, most of them from developing countries, varied between 150/100,000 patients in Turkey and 2450/100,000 patients in India. Of note, high prevalence of extrapulmonary forms as well as elevated TB-associated mortality was reported in most series. TB was more frequent in SLE patients than expected in the general population. We did not see any cases of disseminated infection and all patients had good response to treatment. Our data compare favourably in terms of incidence, severity and outcome with those from highly endemic areas.     

Tuberculosis as a risk factor for systemic lupus erythematosus: results of a nationwide study in Taiwan

A previous study, with relatively small number of patients, showed that prior Mycobacterium tuberculosis (TB) may precipitate SLE in patients from endemic areas. The purpose of the study was to investigate the relationship between prior TB infection and systemic lupus erythematosus (SLE) from the National Health Insurance Research Database (NHIRD) in Taiwan. Cases of SLE and TB were identified from the NHIRD with corresponding ICD-9 codes 710.0 and 011-018, respectively, from January 2000 to December 2008. A total of 2,721 cases of SLE and 10,823 control subjects were included in data analysis. The average annual incidence rate was 8.1 per 100,000. The annual incidence rates of SLE decreased from 6.38 per 100,000 to 2.55 per 100,000 during 2000–2008. Compared with the control subjects, SLE patients were more likely to be white collar workers (P?=?0.0005), reside in highly urbanized areas (P?=?0.0140), and have higher incomes (P?=?0.0088). TB was much more prevalent in SLE patients than in the control subjects (1.8 vs. 0.9%, P?<?0.001). The mean time interval between diagnosis of TB and SLE was 45.58?±?39.0?months. On multivariate analysis, TB was the greatest potential risk factor for precipitating SLE (OR?=?2.11, 95% CI?=?1.49–3.00). In addition, patients with co-existing TB and DM had a higher risk of SLE than the control group (OR?=?3.91, 95% CI 1.84–8.31). In conclusion, this study suggests that there is an increased risk of precipitating SLE among patients with TB in Taiwan from a nationwide health insurance research dataset. Mycobacterial infections could trigger autoimmune diseases in experimental studies. Furthermore, a study with relatively small number of patients revealed that prior TB may precipitate SLE in patients from endemic areas. There is an increased risk of precipitating SLE among patients with TB in Taiwan from a nationwide health insurance research dataset during a 9-year period.     

The changing pattern of tuberculosis and HIV co-infection in immigrants and Spaniards in the last 20 years

OBJECTIVES: To evaluate the impact of immigration on tuberculosis (TB)-HIV co-infection in Spain in a prospective cohort of HIV patients. METHODS: Among 7761 HIV patients, we evaluated 1284 with at least one episode of TB between 1987 and 2006. Variables were compared between immigrants and Spaniards. RESULTS: Incidence of TB decreased from 20 to five cases per 100 patient-years in 2006 (P<0.01) and was always higher in immigrants than in Spaniards. The proportion of immigrants increased, reaching almost 50% of both new cases of HIV and TB-HIV co-infection in 2006. In 34.4% of patients, TB and HIV infection were diagnosed within the same year; simultaneous diagnosis was more frequent in immigrants (83.3%vs. 16.7%, P<0.001). Mortality was associated independently with age [hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.01-1.05], TB diagnosis before 1996 (HR 2.6, 95% CI 1.8-3.6), use of highly active antiretroviral treatment (HR 0.494, 95% CI 0.37-0.66) and CD4 cell count at TB diagnosis (HR 0.996, 95% CI 0.995-0.997). CONCLUSIONS: Immigrants have a major impact on the incidence of TB in HIV patients, slowing down the decreasing trend in Spain. Simultaneous diagnosis of the co-infection in immigrants reveals a need to intensify HIV case finding in immigrants in Spain.     

Tuberculosis trends in Madrid, 1994-2003: impact of immigration and HIV infection.

SETTING: Tuberculosis (TB) cases reported from nine districts of Madrid, where the percentage of immigrant population varied from 1.9% in 1996 to 12.2% in 2003. OBJECTIVE: To describe the trends in TB incidence from 1994 to 2003. DESIGN: Observational study. RESULTS: Between 1994-1995 and 2002-2003, the TB rate decreased from 48.5 (95% CI 45.8-51.1) to 23.3 per 100000 population (95% CI 21.5-25.1) (P < 0.001). The percentage of TB cases co-infected with HIV decreased from 55.9% in 1994 to 14.3% in 2003 (P < 0.001), whereas TB cases in foreigners increased from 2.6% in 1994 to 33.7% in 2003 (P < 0.001). CONCLUSION: Although the TB rates showed a marked decrease in the study period, the increasing impact of immigration contributed to slowing down the trend.