Systemic lupus erythematosus and the risk of malignancy.

The objective of this study was to determine the relative risks of malignancy and of site-specific malignancies in patients with systemic lupus erythematosus (SLE). A cohort of 297 patients (91% Caucasian) with SLE were seen between 1975 and 1994 and followed for a mean of 12 years at the University of Saskatchewan Rheumatic Disease Unit. Expected cancer incidence rates were determined based on Province of Saskatchewan population statistics matched to each study patient for age, sex and calendar year of follow-up. Standardized incidence ratios (SIRs) of observed to expected cancers and 95% confidence intervals (95% CI) were calculated. A total of 27 cases of cancer were observed, whereas only 16.9 were expected (SIR 1.59 (95% CI 1.05-2.32)). For site-specific malignancies, an excess of cancer of the cervix (SIR 8.15 (95% CI 1.63-23.81)) as well as hemopoietic malignancy (SIR 4.9 (95% CI 1.57-11.43)) was found. The hemopoietic cancers were predominantly non-Hodgkin's lymphoma (SIR 7.01 (95% CI 1.88-17.96)). We did not find an association of malignancy with known risk factors, including use of cytotoxic agents. Increased risk of malignancy, notably non-Hodgkin's lymphoma and perhaps cervical cancer, should be regarded as a complication of SLE.     

Incidence of malignancy in Japanese patients with rheumatoid arthritis

To determine the incidence of malignancy and site-specific malignancies in Japanese patients with rheumatoid arthritis (RA). In a prospective large observational cohort study named IORRA, 7,566 patients with RA were enrolled from April 2001 to April 2005 and were followed up to October 2005. Occurrence of malignancy was originally collected by patient reports of IORRA survey biannually from April 2001 to October 2005, and was confirmed by medical records. Standardized incidence rate (SIR) of the observed-to-expected cancer incidence and 95% confidence intervals (95% CI) were then calculated. Factors obtained at first enrollment in IORRA were assessed for association with risk of malignancy using the Cox proportional hazards model. A total of 177 malignancies in 173 patients (58 in men, 115 in women) were identified during the observation period of 25,567 person-years. The age- and sex-standardized incidence rate of malignancy was 437.1 (men, 706.8; women, 366.1) per 100,000 person-years. The SIR of malignancy was slightly excess (SIR 1.18, [95% CI 1.02–1.37]) in all patients, but 1.29 (95% CI 0.99–1.67) in men, and 1.13 (95% CI 0.94–1.36) in women. A significant excess of lymphoma (SIR 6.07, [95% CI 3.71–9.37]) and lung cancer (SIR 2.29, [95% CI 1.57–3.21]), whereas decreased incidence of colorectal cancer (SIR 0.49, [95% CI 0.26–0.83]), were found. Male gender and older age were identified as risk factors for malignancy. A slight excess in the incidence of overall malignancy and highly excess of lymphoma in Japanese RA patients was demonstrated.     

Risk for malignancy in rheumatoid arthritis patients treated with biological disease-modifying antirheumatic drugs compared to the general population: A nationwide cohort study in Japan

Objectives: To investigate and compare the risk for malignancy in rheumatoid arthritis (RA) patients treated with biologics in Japan to the general population.

Methods: Data for 14,440 patients from 335 institutions who were given infliximab, etanercept, adalimumab, golimumab, tocilizumab, or abatacept were retrieved from the SafEty of biologics in Clinical Use in Japanese patients with RhEumatoid arthritis (SECURE) database.

Results: We identified 333 incidents of malignancies in 320 patients during 49,320 patient-years (PY). The age- and sex-standardized incidence rate (ASR) (95% confidence interval [CI]) for overall malignancy of the SECURE cohort was 313.9/10⁵ PY (271.4–361.3), and the standardized incidence rate ratio (SIR) (95% CI) was 0.745 (0.667–0.826). The ASR was decreased compared to the estimated incidence rate of malignancies in the Japanese general population (462.4/10⁵ PY). The SIRs for site-specific nonhematopoietic malignancies of the SECURE cohort were not significantly elevated compared to the Japanese general population. A significant increase of SIR for malignant lymphoma (6.183, 95% CI, 4.809–7.643) was found in the SECURE cohort, similar to or slightly higher than the SIR previously reported from Japanese cohorts for RA patients.

Conclusions: Continued vigilance with larger numbers of patients, longer observation periods, and inclusion of different biologics are recommended.     

No overall increased risk of cancer in patients with rheumatoid arthritis: a nationwide dynamic cohort study in Taiwan

The association between rheumatoid arthritis (RA) and cancer is still controversial. This study aimed to estimate cancer incidence (both overall and site-specific) among patients with RA and to determine whether their cancer risk was higher than in the general population. We used the nationwide dynamic cohort from the National Health Insurance Research Database of Taiwan and obtained a total of 30,504 patients with no history of cancer who were newly diagnosed with RA between 1996 and 2008; they were followed up until 2010. Standardized incidence ratios (SIR) by age for various types of cancer were calculated in 5-year calendar periods by 5-year age intervals (quinquinquennium) to compare elevated risk of increasing age and increased cancer rate in later calendar years in Taiwan. During 225,432 person-years of follow-up, 1,595 cancers occurred, corresponding to 7.08 per 1,000 person-years. The SIR for all cancers was 0.93 (95 % CI 0.88–0.97). Most cancers were found in the first 2 years after diagnosis of RA, but the incidence decreased afterward. A significant excess of Hodgkin’s lymphoma (SIR 3.31, 95 % CI 1.24–8.81) and non-Hodgkin’s lymphoma (SIR 3.18, 95 % CI 2.64–3.83) was seen among patients with RA, whereas the risk of colorectal cancer was 29 % lower than the general population. In conclusion, this study showed that patients with RA do not have increased overall risk of cancers but have higher risk of hematologic malignancies and lower risk of colorectal cancer, than the general population.     

High incidence of potentially virus‐induced malignancies in systemic lupus erythematosus: A long‐term followup study in a Danish cohort

Objective

Patients with systemic lupus erythematosus (SLE) seem to experience an increased prevalence of oncogenic virus infections. The aim of the present study was to investigate whether SLE patients have an increased risk of virus‐associated malignancies, defined as malignancies potentially caused by virus infection.

Methods

A hospital‐based cohort of 576 SLE patients was linked to the Danish Cancer Registry. The cohort was followed up for malignancies from the date of SLE diagnosis, and standardized incidence ratios (SIRs) were calculated for various forms of cancer.

Results

The median duration of followup was 13.2 years. Compared to the general population, the patients experienced an increased overall risk of cancer (SIR 1.6 [95% confidence interval (95% CI)] 1.2–2.0). We observed an increased risk of virus‐associated cancers combined (SIR 2.9 [95% CI 2.0–4.1]). Among human papillomavirus (HPV)–associated malignant and premalignant conditions, high risk was found for anal cancer (SIR 26.9 [95% CI 8.7–83.4]), vaginal/vulvar cancer (SIR 9.1 [95% CI 2.3–36.5]), epithelial dysplasia/carcinoma in situ of the uterine cervix (SIR 1.8 [95% CI 1.2–2.7]), and nonmelanoma skin cancer (SIR 2.0 [95% CI 1.2–3.6]). Increased SIRs were also found for other potentially virus‐induced cancer types (liver cancer SIR 9.9 [95% CI 2.5–39.8], bladder cancer SIR 3.6 [95% CI 1.4–9.7], and non‐Hodgkin's lymphoma SIR 5.0 [95% CI 1.9–13.3]).

Conclusion

The patients in this SLE cohort experienced an increased risk of HPV‐associated tumors and other potentially virus‐induced cancers during long‐term followup. Our findings call for clinical alertness to oncogenic virus infections in SLE patients.

     

Cancer in rheumatoid arthritis: occurrence, mortality, and associated factors in a South European population

OBJECTIVES: To estimate the prevalence, incidence, mortality, and predictors of cancer in patients with rheumatoid arthritis (RA). METHODS: We compared the incidence of cancer and the mortality by cancer in a cohort of 789 randomly selected RA patients (1999-2005) with the expected ones in the general population. We estimated standardized incidence ratios (SIR) and standardized mortality ratios (SMR) by indirect age and sex standardization. Additionally, we analyzed by generalized linear models the association of various predictors with cancer incidence, obtaining incidence rate ratios (IRR) with 95% confidence intervals (CI). RESULTS: The SIR of cancer in RA is 1.23 (95% CI: 0.78-1.85). By cancer type, there is an increased risk of leukemia, non-Hodgkin's lymphoma, and lung cancer in RA compared with the general population of the same sex and age. The SMR of cancer is 1.0 (95% CI: 0.53-1.7). By cancer type, RA patients with lung or kidney cancer have higher mortality than expected. Being male, elderly, with longstanding disease, and having used any cytotoxic drugs apart from methotrexate are confirmed as predictive factors for cancer. Additional independent predictors are increases in blood leukocyte counts (IRR per 3000 u/mm3 increase: 1.88 (95% CI: 1.6 -2.1)) and decreases in serum hemoglobin (IRR per 2 g/l decrease: 1.88 (95% CI: 1.19 -2.94)). CONCLUSIONS: The overall incidence and mortality of cancer in RA is not greater than the expected, although there is an increased risk of hematopoietic and lung cancers in RA patients compared with the general population. Hemoglobin and leukocyte counts may help to identify RA patients at risk for cancer.     

Risk of malignancy in children with juvenile idiopathic arthritis not treated with biologic agents

Objective

To estimate the relative risk of incident cancer diagnosis among patients with juvenile idiopathic arthritis (JIA) compared to patients without JIA.

Methods

A cohort of biologics‐naive patients diagnosed with JIA between 1998 and 2007 and a matched cohort of comparators without JIA were assembled from the PharMetrics Patient‐Centric Database. The primary outcome was any incident malignancy, excluding nonmelanoma skin cancer and carcinoma in situ. Claims profiles of patients with any cancer‐related diagnosis codes were reviewed to determine outcomes. Incidence rates and 95% confidence intervals (95% CIs) of cancer were calculated and compared between cohorts using Cox proportional hazards regression. Standardized incidence ratios (SIRs) for each cohort compared to the general population were calculated using reference rates from the US Surveillance, Epidemiology, and End‐Results (SEER) program.

Results

The JIA and non‐JIA cohorts included 3,605 and 37,689 patients, respectively, with a mean age of 11 years. The incidence rates of cancer were 67.0 (95% CI 1.3–132.5) cases/100,000 person‐years (PY) for JIA and 23.2 (95% CI 12.2–34.2) cases/100,000 PY for non‐JIA. The risk of cancer associated with biologics‐naive JIA was elevated (hazard ratio 2.8, 95% CI 0.9–8.3). The JIA cohort had a significantly elevated SIR of 4.0 (95% CI 2.6–6.0); the non‐JIA cohort SIR was not significantly above SEER rates (SIR 1.4, 95% CI 0.6–2.6).

Conclusion

We found a nearly 3‐fold increased risk of cancer in biologics‐naive JIA patients, which approached significance despite the small number of outcomes. This finding suggests an elevated underlying risk of cancer in this disease population.     

Incidence of melanoma and other malignancies among rheumatoid arthritis patients treated with methotrexate

OBJECTIVE: To determine cancer risk in a cohort of 459 rheumatoid arthritis (RA) patients treated with methotrexate in community practice. METHODS: All RA patients who started methotrexate prior to June 1986 and were attending 1 of 6 rheumatologists were studied. Demographic data were matched to the State Cancer Registry to identify all malignancies (except nonmelanoma skin cancer) for 1983-1998, and to the National Death Index to identify all deaths to the end of 1999. Followup started on the date when methotrexate was started and ended either on the last confirmed date on which the patient was seen by the rheumatologist or at death. Standardized incidence ratios (SIRs) were calculated using state population cancer rates stratified by sex, age (in 5-year groups), and calendar year. RESULTS: There were 4,145 person-years of followup (average 9.3 years). Eighty-seven malignancies were identified (14 before, 64 during, and 9 after the followup period). There was an estimated 50% excess risk of malignancy among methotrexate-exposed RA patients relative to the general population (SIR 1.5, 95% confidence interval [95% CI] 1.2-1.9), with a 3-fold increase in melanoma (SIR 3.0, 95% CI 1.2-6.2), a 5-fold increase in non-Hodgkin's lymphoma (SIR 5.1, 95% CI 2.2-10.0), and an almost 3-fold increase in lung cancer (SIR 2.9, 95% CI 1.6-4.8). CONCLUSION: Compared with the general population, methotrexate-treated RA patients have an increased incidence of melanoma, non-Hodgkin's lymphoma, and lung cancer. There may be a role for regular skin cancer screening for all RA patients, particularly those receiving immunosuppressive therapy.     

Prevalence of Helicobacter pylori infection and risk of upper gastrointestinal ulcer in patients with rheumatoid arthritis in Japan

Abstract

We evaluated the prevalence of Helicobacter pylori infection and the association of H. pylori infection and/or nonsteroidal anti-inflammatory drug (NSAID) use with upper gastrointestinal (UGI) ulcers in a cohort of Japanese patients with rheumatoid arthritis (RA). Using the clinical database of the cohort of RA patients and the serum titers of H. pylori antibody, 1815 patients were analyzed. Clinical data were successfully collected for 1529 patients over 2 years, and the history of NSAID use and the occurrence of newly diagnosed UGI ulcer were ascertained by patient self-reports and confirmed by their medical records. A total of 871 patients (49.3%) were H. pylori antibody-positive. Rates of positivity for H. pylori in patients with and without NSAID use were 47.5% and 54.7%, respectively (odds ratio = 0.75, 95% confidence intervals [CI]: 0.58–0.96). The incidence of newly diagnosed UGI ulcer was 0% in the H. pylori?/NSAID? group, 1.24% in the H. pylori?/NSAID+ group, 1.06% in the H. pylori+/NSAID? group, and 3.46% in the H. pylori+/NSAID+ group. The odds ratios of H. pylori infection and NSAID for the occurrence of new UGI ulcers after adjusting for age and sex were 2.97 (95% CI: 1.19–7.38) and 4.31 (95% CI: 0.57–32.4), respectively. Although the prevalence of H. pylori antibody was low in patients with RA compared with that in healthy Japanese individuals, H. pylori infection was a significant risk factor for UGI ulcer in patients with RA.     

Is there a risk of cancer development after Campylobacter infection?

Abstract

Objective. All Campylobacter jejuni species produce a genotoxin, which induce DNA double strand breaks, could lead to an increased risk of cancer especially in the gastro-intestinal tract. Material and methods. All individuals in Stockholm County who tested positive with C. jejuni between 1989 and 2006 were included. The cohort was followed-up until December 31, 2007 for the occurrence of cancer, overall and site specific. Standard incidence ratios (SIR) with 95% confidence intervals (CI) were calculated by comparisons with the background population. Results. There were 16,276 individuals who tested positive for C. jejuni generating 124,387 person years. Excluding the first year of follow-up the overall risk for cancer did neither differ from that expected SIR = 0.95 (95% CI 0.82–1.09) nor after10 years or more of follow-up; SIR = 0.91 (95% CI 0.71–1.16). There was no increased risk for cancer in the gastro-intestinal tract, but there were significantly increased risks for melanomas SIR = 1.84 (95% CI 1.27–2.57) and squamous cell skin cancer SIR = 1.52 (95% CI 1.01–2.19) while a significantly decreased risk of respiratory cancers among males SIR = 0.32 (95% CI 0.12–0.70) was observed. Conclusions. Our results indicate no excess risks of malignancies following an infection by C. jejuni at least during the first decade. Furthermore, the finding of a decreased risk of respiratory cancers could be of interest, if the results are reproduced in future studies in other populations.     

Malignancies in Wegener's granulomatosis: incidence and relation to cyclophosphamide therapy in a cohort of 293 patients

OBJECTIVE: To describe the incidence of malignancies in a cohort of Danish patients with Wegener's granulomatosis (WG) and to investigate the cancer risk associated with cyclophosphamide (CYC) -therapy in WG. METHODS: In total, 293 patients diagnosed with WG between 1973 and 1999 were studied. Cancer incidence in the cohort was assessed through 2003 by linkage to the Danish Cancer Registry and compared to that of the general population by calculation of standardized incidence ratios (SIR). Analyses were stratified according to treatment with low cumulative CYC doses (< or = 36 g) and high doses (> 36 g, corresponding to treatment with 100 mg CYC/day for > 1 year). RESULTS: Fifty cancers occurred during 2121 person-years of followup (SIR of cancer of 2.1, 95% CI 1.5-2.7). Significantly increased SIR were observed for acute myeloid leukemia (AML; SIR 19.6, 95% CI 4.0-57), bladder cancer (SIR 3.6, 95% CI 1.2-8.3), and non-melanoma skin cancers (SIR 4.7, 95% CI 2.8-7.3). Leukemias and bladder cancers were diagnosed 6.9-18.5 years after initiation of CYC therapy. The risk of these malignancies was not increased for patients who never received CYC or for patients treated with cumulative CYC doses < or = 36 g. In contrast, high risks of AML (SIR 59.0, 95% CI 12-172) and bladder cancer (SIR 9.5, 95% CI 2.6-24) were observed for patients treated with cumulative CYC doses > 36 g. CONCLUSION: Treatment with high cumulative CYC doses implies a substantial risk of late-occurring, serious malignancies in WG. Patients with WG should be monitored for development of cancer for several decades after cessation of CYC therapy. These findings emphasize the need for development of new treatment regimens in WG.     

The Risk of Cancer in Patients with Benign Anal Lesions: A Nationwide Population-based Study

Objective

To evaluate the risk of cancer among patients diagnosed with hemorrhoids and benign anal inflammatory lesions.

Methods

A population-based, retrospective cohort study was conducted that included patients diagnosed with hemorrhoids or benign inflammatory anal lesions (eg, anal fissure, fistula, and perianal abscesses) that were registered in the National Health Insurance Research Database in Taiwan between January 1, 2000 and December 31, 2010. Standardized incidence ratios (SIRs) were calculated to compare the cancer incidence of these patients to the general population.

Results

During a median observation period of 6.23 years, 3080 cancers developed among 70,513 hemorrhoid patients, with a follow-up period of 438,425.6 person-years, entailing the SIR of 1.52 (95% confidence interval [CI], 1.47-1.58). Increased cancer risk (SIR 1.16; 95% CI, 1.11-1.21) was still noted even after excluding the first year of observation. Significant long-term risk for colorectal cancer (SIR 1.50; 95% CI, 1.35-1.66) and prostate cancer (SIR 1.40; 95% CI, 1.17-1.66) was observed after corrections were made for multiple comparisons. In contrast, there was no remarkable increase in cancer risk for patients with inflammatory anal lesions when cancers detected within the first year of diagnosis were excluded.

Conclusion

The presence of hemorrhoids is associated significantly with a long-term risk of developing colorectal cancer or prostate cancer. In contrast, benign inflammatory anal lesions do not appear to increase the risk of malignancy.     

Prevalence of Helicobacter pylori infection and risk of upper gastrointestinal ulcer in patients with rheumatoid arthritis in Japan

We evaluated the prevalence of Helicobacter pylori infection and the association of H. pylori infection and/or nonsteroidal anti-inflammatory drug (NSAID) use with upper gastrointestinal (UGI) ulcers in a cohort of Japanese patients with rheumatoid arthritis (RA). Using the clinical database of the cohort of RA patients and the serum titers of H. pylori antibody, 1815 patients were analyzed. Clinical data were successfully collected for 1529 patients over 2 years, and the history of NSAID use and the occurrence of newly diagnosed UGI ulcer were ascertained by patient self-reports and confirmed by their medical records. A total of 871 patients (49.3%) were H. pylori antibody-positive. Rates of positivity for H. pylori in patients with and without NSAID use were 47.5% and 54.7%, respectively (odds ratio = 0.75, 95% confidence intervals [CI]: 0.58–0.96). The incidence of newly diagnosed UGI ulcer was 0% in the H. pylori−/NSAID− group, 1.24% in the H. pylori−/NSAID+ group, 1.06% in the H. pylori+/NSAID− group, and 3.46% in the H. pylori+/NSAID+ group. The odds ratios of H. pylori infection and NSAID for the occurrence of new UGI ulcers after adjusting for age and sex were 2.97 (95% CI: 1.19–7.38) and 4.31 (95% CI: 0.57–32.4), respectively. Although the prevalence of H. pylori antibody was low in patients with RA compared with that in healthy Japanese individuals, H. pylori infection was a significant risk factor for UGI ulcer in patients with RA.     

Malignancy in systemic lupus erythematosus: a nationwide cohort study in Taiwan

BackgroundAn increased risk of malignancy in patients with systemic lupus erythematosus has been reported, but rarely in Asian populations. We aimed to investigate the relative risk of cancer and to identify the high-risk group for cancer in patients with lupus.MethodsWe conducted a retrospective, nationwide cohort study that included 11,763 patients with lupus without a history of malignancies, using the national health insurance database of Taiwan from 1996 to 2007. Standardized incidence ratios (SIRs) of cancers were analyzed.ResultsA total of 259 cancers were observed in patients with lupus. An elevated risk of cancer among those with systemic lupus erythematosus was noted (SIR 1.76; 95% confidence interval [CI] 1.74-1.79), especially for hematologic malignancies (SIR 4.96; 95% CI 4.79-5.14). Younger patients had a greater risk ratio of cancer than the general population, and the risk ratio decreased with age. The risk ratio of cancer decreased with time, yet remained elevated compared with that of the general population. The risk of non-Hodgkin lymphoma was greatest (SIR 7.27) among hematologic cancers. Among solid tumors, the risk was greatest for cancers of the vagina/vulva (SIR 4.76), nasopharynx (SIR 4.18), and kidney (SIR 3.99). An elevated risk for less common cancers, including those of the brain, oropharynx, and thyroid glands, was also observed.ConclusionPatients with lupus are at increased risk of cancers and should receive age- and gender-appropriate malignancy evaluations, with additional assessment for vulva/vagina, kidney, nasopharynx, and hematologic malignancy. Continued vigilance for development of cancers in follow-up is recommended.     

The risk of lymphoma development in autoimmune diseases: a meta-analysis

BACKGROUND: The risk of development of non-Hodgkin lymphoma (NHL) in autoimmune patients has been investigated in several cohort studies. These studies revealed inconclusive results. To shed some light on this controversy, we conducted a meta-analysis of all available cohort studies linking systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sj?gren syndrome (pSS) to the risk of NHL development. METHODS: We searched the PubMed database (1974 to April 2005) for English-language cohort studies using the key words systemic lupus erythematosus, SLE, rheumatoid arthritis, RA, Sj?gren syndrome, or SS; non-Hodgkin lymphoma; and relative risk, RR, standardized incidence rate, or SIR. All cohort studies that used established diagnostic criteria for SLE, RA, and pSS; had histologic confirmation of NHL; and provided standardized incidence rates (SIRs) were included in the meta-analysis. RESULTS: The 20 studies chosen for the analysis included 6 for SLE, 9 for RA, and 5 for pSS. Overall, the meta-analysis suggested extreme heterogeneity among the studies (P < .01; I2 > 70%), high risk of NHL development for pSS (random effects SIR, 18.8; 95% confidence interval [CI], 9.5-37.3); moderate risk for SLE (random effects SIR, 7.4; 95% CI, 3.3-17.0); and lower risk for RA (random effects SIR, 3.9; 95% CI, 2.5-5.9). In RA, the random effects SIRs of NHL with conventional antirheumatic treatment, cytotoxic treatment, and treatment with a biological agent were 2.5 (95% CI, 0.7-9.0), 5.1 (95% CI, 0.9-28.6), and 11.5 (95% CI, 3.7-26.9), respectively. CONCLUSIONS: Rheumatic disease may present a potential risk factor for development of NHL. In this regard, we focused on the underlying pathophysiologic mechanisms related to lymphomagenesis in pSS, SLE, and RA, to justify the varying potential for and background of NHL development.     

Risk of malignancies in autoimmune hepatitis type 1 patients with a long‐term follow‐up in Japan

Aim

The risk of malignancies in autoimmune diseases is high and is regarded to be due to immunological abnormalities, the use of immunosuppressive agents, and/or chronic inflammation. The aim of this study was to investigate the incidence and risk of malignancies in patients with autoimmune hepatitis (AIH) type 1 in Japan.

Methods

Two hundred and fifty‐six patients diagnosed with AIH were enrolled. A person‐year calculation was carried out for AIH patients, and the numbers of expected events were clarified using data from “The Monitoring of Cancer Incidence in Japan Project” in order to examine the standard incident rate (SIR) of each type of malignancy. Biochemical data regarding carcinogenesis and its background factors were also examined.

Results

Twenty‐seven patients (10.5%) developed malignancies; 11 (4.3%) with hepatobiliary cancer and 16 (6.3%) with extrahepatic malignancies. The overall SIR for malignancies in AIH was significantly high at 2.04 (95% confidence interval [CI], 1.34–2.96), and was high among female patients at 2.49 (95% CI, 1.60–3.71). The SIR for hepatobiliary cancer was 14.14 (95% CI, 7.05–25.30), and was markedly high for female patients at 21.83 (95% CI, 10.45–40.16). The SIR for oral/pharyngeal cancer was significantly high for female patients at 14.61 (95% CI, 1.64–52.77). The risk factors for hepatobiliary cancer at the diagnosis of AIH were low levels of alanine aminotransferase (P = 0.0226), low platelet counts (P < 0.0001), and cirrhosis (P = 0.0004). The risk factor for extrahepatic malignancy was relapse of AIH (P = 0.0485).

Conclusion

The risk of malignancies was generally high among AIH patients. Those with the risk factors of malignancies should be carefully followed up.     

Malignancy in systemic lupus erythematosus

Objective. To estimate the risk of cancer in patients with systemic lupus erythematosus (SLE). Methods. Patients with SLE (n = 724) have been followed prospectively, for 24 years, at the University of Toronto Lupus Clinic. The diagnosis of cancer was confirmed by histologic or autopsy reports. Standardized rates of cancer and standardized incidence rates (SIR) (ratio of observed-to-expected cancers) were used to estimate the risk for cancers. Results. Twenty-four cancers were identified in 23 SLE patients (3.2%) during 7,233 patient-years of followup. Compared with the Ontario population, the overall estimated risk for all cancers was not increased in the lupus cohort (SIR 1.08, 95% confidence interval 0.70–1.62). A 4.1-fold increased risk for hematologic cancers was observed, due mainly to an increased risk of non-Hodgkin's lymphoma. The risk for cancer was significantly lower in the SLE cohort compared with patients with rheumatoid arthritis (RA) and systemic sclerosis (SSc). Conclusion. SLE is associated with a lower risk of all cancers compared with RA and SSc, but an increased risk for non-Hodgkin's lymphoma compared with the general population.     

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.     

Incidence of malignancies in patients with juvenile idiopathic arthritis: A retrospective single-center cohort study in Germany

Objectives: In recent years, concern has been raised about Juvenile Idiopathic Arthritis (JIA) that it could be associated with an increased risk for malignancies. Therefore, the cancer incidence in the JIA patients was evaluated and compared to the cancer incidence in the German population.

Methods: A retrospective single-center hospital-based cohort study was performed using data on the JIA patients treated between 1952 and 2010 at the German Center for Pediatric and Adolescent Rheumatology (GCPAR) (Garmisch-Partenkirchen, Germany). Self-administered standardized questionnaires were sent out in 2012. Standardized incidence ratios (SIRs) and their corresponding 95% confidence intervals (95%CIs) were calculated.

Results: The study cohort consisted of 3691 JIA patients, and the response rate was 66%. Patients age ranged from 3 to 73 years of which 64% were female. Total follow-up time was 60,075 person-years; a history of malignancy was reported by 47 patients. Most common types of cancer were melanoma (n?=?11), cervical cancer (n?=?8) and breast cancer (n?=?7). The overall SIR for women was 1.19 (95%CI: 0.77; 1.60) and for men was 0.67 (95%CI: 0.27; 1.07). The SIR for melanoma was 3.21 (95%CI: 1.60; 5.73) in women, whereas in men no melanoma cases were observed.

Conclusion: Although no overall increased cancer risk was found, results suggest that the risk of melanoma might be increased in female JIA patients.     

Bisphosphonate increases risk of gastroduodenal ulcer in rheumatoid arthritis patients on long-term nonsteroidal antiinflammatory drug therapy

Background  Rheumatoid arthritis (RA) patients are at increased risk of peptic ulcers (PU) induced by nonsteroidal antiinflammatory drugs (NSAIDs). However, the impact of potential drug interactions on the development of PU has yet to be determined in a daily clinical setting. The aim was to estimate the clinical important interactions for PU presented by comedication in Japanese RA outpatients on long-term NSAID treatment. Methods  This retrospective cohort study enrolled 196 consecutive RA outpatients on NSAID medication for at least 3 months. Potential risk factors for endoscopic PU were analyzed in RA outpatients on longterm NSAID treatment. Results  PU incidence was 31% with bisphosphonate co-therapy and 17% without the co-therapy. PU incidence was only 5% in subjects with proton pump inhibitors (PPI) or prostaglandin E1 analogues (PG) co-therapy, 14% with histamine-H₂ receptor antagonists(H2RA) co-therapy, and 27% without anti-ulcer agents. In multivariate logistic regression analysis, bisphosphonate co-therapy remained a significant risk factor for PU (OR, 2.29; 95% CI, 1.09–4.81). Other risk factors for ulcer development were advanced age (greater than 60 years) and smoking (OR, 2.58; 95% CI, 1.03–6.49 and OR, 2.71; 95% CI, 1.13–5.53, respectively.) Factors that significantly reduced the incidence of PU were H2RA or PPI/PG cotherapies (OR, 0.29; 95% CI, 0.12–0.68.). Conclusions  Bisphosphonate co-therapy as well as advanced age and smoking was found to be a significant risk factor in PU, while co-therapies of standard-dose H2RA or PPI/PG proved effective in preventing PU in Japanese RA patients on long-term NSAID treatment.