Mortality and Incidence of Malignancy in Korean Patients with Rheumatoid Arthritis

2011 ◽  
Vol 39 (2) ◽  
pp. 226-232 ◽  
Author(s):  
YUN JUNG KIM ◽  
JEE-SEON SHIM ◽  
CHAN-BUM CHOI ◽  
SANG-CHEOL BAE

Objective.To determine the standardized mortality ratio (SMR) and standardized incidence ratio (SIR) for malignancy in Korean patients with rheumatoid arthritis (RA).Methods.We enrolled 1534 patients with RA who fulfilled the American College of Rheumatology criteria, from October 2001 to December 2007. Baseline assessment included sociodemographic variables, laboratory findings including rheumatoid factor, anticitrullinated protein antibody, functional class, radiological stage, medication, and the Korean version of the Health Assessment Questionnaire. We used the national mortality rate from 2001 to 2007 from the Korean National Statistical Office (KNSO) and the incidence rate from the Korean Central Cancer Registry (KCCR) from 2001 to 2007 as comparison data for estimates of SMR and SIR. Confidence intervals were calculated based on the Poisson distribution.Results.There were 57 deaths in 6683 person-years of followup. The number of expected deaths (derived from the KNSO) was 42.33 and the SMR for patients with RA was 1.35 (95% CI 1.02–1.74). The main causes of death were malignancy, cardiovascular disease, and respiratory disease. In the cause-specific SMR, deaths from respiratory disease, especially from interstitial lung disease (ILD) and pneumonia, were significantly higher than expected: 4.66 (95% CI 2.13–8.85) for all respiratory disease, 18.18 (95% CI 2.20–65.64) for ILD, and 10.26 (95% CI 2.79–26.26) for pneumonia. Thirty malignancies had occurred in 1501 patients. The number of expected malignancies derived from the KCCR was 34.91, yielding a SIR for cancer of 0.86 (95% CI 0.58–1.23).Conclusion.Our study demonstrates that the SMR was slightly higher in patients with RA, but the incidence rates of malignancies were not significantly different from the general population. But deaths from respiratory diseases were significantly higher.

2014 ◽  
Vol 41 (6) ◽  
pp. 1077-1087 ◽  
Author(s):  
Joel M. Kremer ◽  
Charles Peterfy ◽  
Anthony S. Russell ◽  
Paul Emery ◽  
Carlos Abud-Mendoza ◽  
...  

Objective.Evaluate the safety and efficacy of longterm abatacept (ABA) treatment over 5 years in methotrexate (MTX)-refractory patients with rheumatoid arthritis (RA).Methods.Patients from the 1-year, double-blind Abatacept in Inadequate Responders to Methotrexate (AIM) study (NCT00048568) received open-label ABA (∼10 mg/kg) in the longterm extension (LTE). Safety was assessed for patients who received ≥ 1 ABA dose, and efficacy for patients randomized to ABA and treated in the LTE. Radiographs were evaluated for changes in Genant-modified Sharp scores.Results.Out of 652 patients, 539 entered the LTE (ABA, n = 378; placebo, n = 161). At Year 5, 72.4% were ongoing; discontinuation rates declined over time. Incidence rates of serious adverse events, serious infections, malignancies, and autoimmune events were 13.87, 2.84, 1.45, and 0.99 events/100 patient-years exposure, respectively. American College of Rheumatology 20 response was 82.3% (n = 373) and 83.6% (n = 268) at years 1 and 5, respectively. Disease Activity Score 28 C-reactive protein (DAS28-CRP) < 2.6 and ≤ 3.2 were achieved by 25.4% and 44.1% of patients at Year 1 (n = 370), and 33.7% and 54.7% at Year 5 (n = 267), respectively. Mean changes in DAS28-CRP and Health Assessment Questionnaire–Disability Index at Year 1 [–2.83 (n = 365) and −0.68 (n = 369)] were maintained at Year 5 [−3.14 (n = 264) and −0.77 (n = 271)] for patients continuing treatment. Of them, 59.5% (n = 291) and 45.1% (n = 235) remained free from radiographic progression at years 1 and 5, respectively.Conclusion.In MTX-refractory patients with RA, longterm ABA treatment was well tolerated and provided consistent safety and sustained efficacy, with high patient retention. Radiographic progression continued to be inhibited with ongoing treatment.


2019 ◽  
Vol 78 (5) ◽  
pp. 586-589 ◽  
Author(s):  
Pomme BM Poppelaars ◽  
Lilian H D van Tuyl ◽  
Maarten Boers

ObjectivesMortality in patients with rheumatoid arthritis (RA) is higher than in the general population. We investigated mortality in the COBRA-trial cohort after 23 years follow-up, compared with a reference sample of the Dutch population.MethodsThe COBRA-trial randomised patients with early RA to sulfasalazine monotherapy (SSZ, n=79) or a combination of SSZ, low-dose methotrexate and initially high, step-down prednisolone (COBRA, n=76). We compared the mortality in the COBRA-trial up to 2017 to a reference sample of the general population in the Netherlands (standardised mortality ratio, SMR), and its relation to early prognostic factors through stepwise Cox regression.ResultsDuration of follow-up in patients alive was mean 23 (range 22–24) years. In total, 44 patients died (28%, SMR=0.80 [95% CI 0.59 to 1.06]); 20 of 75 COBRA patients (27%, SMR 0.75 [0.47 to 1.14]) and 24 of 79 SSZ patients (30%, SMR 0.85 [0.56 to 1.25]); p=0.61). In the reference sample of the general population, 55 people (36%) died. 5 factors were significantly associated with increased mortality hazard: damage progression at 28 weeks; high Health Assessment Questionnaire (HAQ) score and absence of HLA-DR 2 or 3; disease duration from start of complaints was also significant, but showed an uninterpretable pattern.ConclusionsThis prospective trial cohort study of early RA is one of the first to show similar mortality compared with the general population after 23 years of follow-up. It confirms that early, intensive treatment of RA has long-term benefits and suggests that treating to target is especially important for patients with poor prognosis.


2012 ◽  
Vol 39 (7) ◽  
pp. 1355-1362 ◽  
Author(s):  
ELENA MYASOEDOVA ◽  
ERIC L. MATTESON ◽  
NICHOLAS J. TALLEY ◽  
CYNTHIA S. CROWSON

Objective.To assess the incidence and mortality impact of upper and lower gastrointestinal (GI) events in rheumatoid arthritis (RA) compared to non-RA subjects.Methods.We identified incident upper and lower GI events and estimated their incidence rates using person-year methods in a population-based incident RA cohort of residents of Olmsted County, Minnesota, USA (1987 American College of Rheumatology criteria first fulfilled between January 1, 1980, and January 1, 2008) and non-RA subjects from the same population.Results.The study included 813 patients with RA and 813 non-RA subjects (mean followup 10.3 and 10.8 yrs, respectively); 68% women; mean age 55.9 yrs in both cohorts. The rate of upper GI events/100 person-years was 2.9 in RA versus 1.7 in the non-RA cohort (rate ratio 1.7, 95% CI 1.4, 2.2); for lower GI events, the rates were 2.1 in RA versus 1.4 in the non-RA cohort (rate ratio 1.5, 95% CI 1.1, 1.9). The incidence of upper GI bleed, perforation, ulcer, obstruction, and any upper GI event in RA declined over calendar time; the incidence of lower GI events remained unchanged. Exposure to glucocorticoids, prior upper GI disease, abdominal surgery, and smoking were associated with lower GI events in RA. Both upper and lower GI events were associated with increased mortality risk in RA.Conclusion.There is increased risk of serious upper and lower GI events in RA compared to non-RA subjects, and increased GI-related mortality in RA. Prominent declines in incidence of upper, but not lower GI events in RA highlight the need for studies investigating lower GI disease in patients with RA.


2011 ◽  
Vol 70 (10) ◽  
pp. 1826-1830 ◽  
Author(s):  
Joel M Kremer ◽  
Anthony S Russell ◽  
Paul Emery ◽  
Carlos Abud-Mendoza ◽  
Jacek Szechinski ◽  
...  

ObjectiveTo evaluate abatacept treatment over 3 years in patients with rheumatoid arthritis (RA) refractory to methotrexate (MTX).MethodsPatients randomised to abatacept or placebo (+MTX) during the 1-year double-blind period of the Abatacept in Inadequate responders to Methotrexate (AIM) trial received open-label abatacept (+MTX) in the long-term extension (LTE). Safety was assessed for patients who received ≥1 dose of abatacept, regardless of randomisation group. Efficacy was assessed for patients randomised to abatacept who entered the LTE.Results433 and 219 patients were randomised and treated with abatacept or placebo, respectively; 378 and 161 entered the LTE. At year 3, 440/539 patients were ongoing. No unexpected safety events were observed in the LTE. By year 3, incidence rates of adverse event and serious adverse events were 249.8/100 and 15.1/100 patient-years, respectively. Incidence rates were generally stable over time. At year 3, 84.8%, 63.4% and 37.5% of patients achieved American College of Rheumatology (ACR) criteria of 20, 50 and 70, respectively, compared with 82.3%, 54.3% and 32.4% of patients at year 1. Mean changes in Genant-modified Sharp scores were reduced progressively over 3 years, with significantly greater inhibition during year 3 compared with year 2 (p=0.022 for total score).ConclusionIn MTX-inadequate responders with RA, abatacept provided consistent safety and sustained efficacy over 3 years. The data suggest an increasing inhibitory disease-modifying effect on radiographic progression.


2014 ◽  
Vol 41 (8) ◽  
pp. 1590-1599 ◽  
Author(s):  
Janet G. Diffin ◽  
Mark Lunt ◽  
Tarnya Marshall ◽  
Jacqueline R. Chipping ◽  
Deborah P.M. Symmons ◽  
...  

Objective.To examine the pattern of disease severity in patients with rheumatoid arthritis (RA) at presentation to the Norfolk Arthritis Register (NOAR) over 20 years.Methods.NOAR is a primary-care–based cohort of patients with recent-onset inflammatory polyarthritis. At baseline, subjects are assessed and examined by a research nurse. The Health Assessment Questionnaire (HAQ) is administered and the DAS28 (28-joint Disease Activity Score) is calculated. Information is collected on disease-modifying antirheumatic drug exposure. In this study, patients (symptom duration of < 2 years at baseline) were grouped into 4 cohorts (Cohort 1: 1990–1994; Cohort 2: 1995–1999; Cohort 3: 2000–2004; Cohort 4: 2005–2008). The American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria for RA were applied retrospectively at baseline. Regression analyses were used to examine whether calendar year of presentation to NOAR was associated with baseline HAQ and DAS28 scores. Potential confounders included age at symptom onset, sex, rheumatoid factor, and anticyclic citrullinated peptide antibody positivity.Results.A total of 1724 patients met the ACR/EULAR 2010 RA criteria at baseline. Unadjusted mean DAS28 scores decreased over time. Calendar year of presentation to NOAR was significantly associated with lower DAS28 scores over time [Y = 4.51 + (–0.56 × year) + (0.44 × year2)]. Although unadjusted median HAQ scores increased over time, calendar year of presentation to NOAR was not significantly associated with HAQ scores [Y = (1.1) + (0.023 × year) + (0.05 × year2)]. Similar results were observed in each subpopulation of patients.Conclusion.While baseline disease activity has lessened slightly over time, there has been no improvement in baseline levels of functional disability.


2016 ◽  
Vol 43 (10) ◽  
pp. 1777-1786 ◽  
Author(s):  
Amir I. Elshafie ◽  
Abdalla D. Elkhalifa ◽  
Sahwa Elbagir ◽  
Mawahib I.E. Aledrissy ◽  
Elnour M. Elagib ◽  
...  

Objective.To compare clinical characteristics and treatment between simultaneously investigated Sudanese and Swedish outpatients with rheumatoid arthritis (RA).Methods.Outpatients with RA from Sudan (n = 281) and Sweden (n = 542) diagnosed according to the 1987 American College of Rheumatology criteria were recruited between December 2008 and September 2010 and compared concerning clinical presentation, treatment, and laboratory findings, including immunoglobulin M with rheumatoid factor (IgM-RF).Results.Sudanese patients had lower inclusion age (median 49 vs 68 yrs), disease duration (48 vs 107 mos), and disease onset age (43 vs 56 yrs) as compared with Swedish patients (p < 0.0001 for all). When stratified concerning the age of inclusion, Swedish patients between 41–50 years had, however, a significantly lower age of onset, with a similar trend for all age groups above 30 years. The female preponderance was higher among Sudanese patients (89.3% vs 72.5%, p < 0.0001), and smoking was nonexistent among Sudanese female patients (p < 0.0001). Erythrocyte sedimentation rate levels and number of tender joints were significantly higher among Sudanese patients. The proportion of IgM-RF positivity was lower among Sudanese patients with RA (52.4% vs 75.5%, p < 0.0001). Higher proportions of Sudanese patients with RA were treated with methotrexate (MTX) and disease-modifying antirheumatic drug combinations, but none of them used biologics. Sudanese patients used lower doses of MTX and sulfasalazine (p < 0.0001) and higher doses of prednisolone (p < 0.0001) than Swedish patients.Conclusion.Sudanese patients with RA have significantly higher disease activity and are often IgM-RF–seronegative. Together with reports from Uganda and Cameroon, our data indicate a cluster of highly active and often seronegative RA in central Africa.


2013 ◽  
Vol 40 (10) ◽  
pp. 1650-1657 ◽  
Author(s):  
Bernard Combe ◽  
Nathalie Rincheval ◽  
Joelle Benessiano ◽  
Francis Berenbaum ◽  
Alain Cantagrel ◽  
...  

Objective.To report the 5-year outcome of a large prospective cohort of patients with very early rheumatoid arthritis (RA), and to identify factors predictive of outcome.Methods.Patients were recruited if they had early arthritis of < 6 months’ duration, had a high probability of developing RA, and had never been prescribed disease-modifying antirheumatic drugs (DMARD) or steroids. Logistic regression analysis was used to determine factors that predict outcome.Results.We included 813 patients from December 2002 to April 2005. Age was 48.1 ± 12.6 years, delay before referral 103.1 ± 52.4 days, 28-joint Disease Activity Score (DAS28) 5.1 ± 1.3, Health Assessment Questionnaire (HAQ) 1.0 ± 0.7; 45.8% and 38.7% had rheumatoid factor or antibodies to cyclic citrullinated peptide (anti-CCP), respectively; 22% had hand or foot erosions; 78.5% fulfilled the American College of Rheumatology/European League Against Rheumatism criteria for RA at baseline and 93.8% during followup. At 5 years, 573 patients were evaluated. The outcome was mild for most patients: disease activity (median DAS28 = 2.5) and HAQ disability (median 0.3) were well controlled over time; 50.6% achieved DAS28 remission and 64.7% low disease activity. Radiographic progression was low (2.9 Sharp unit/year) and only a few patients required joint surgery. Nevertheless, some patients developed new comorbidities. During the 5 years, 82.7% of patients had received at least 1 DMARD (methotrexate, 65.9%), 18.3% a biological DMARD, and about 60% prednisone at least once. Anti-CCP was the best predictor of remaining in the cohort for 5 years, of prescription of synthetic or biologic DMARD, and of radiographic progression.Conclusion.The 5-year outcome of an early RA cohort in the 2000s was described. Anti-CCP was a robust predictor of outcome. The generally good 5-year outcome could be related to early referral and early effective treatment, key processes in the management of early RA in daily practice.


2011 ◽  
Vol 38 (11) ◽  
pp. 2362-2368 ◽  
Author(s):  
ALVIN F. WELLS ◽  
RENE WESTHOVENS ◽  
DIANE MONIZ REED ◽  
LUCIANA FANTI ◽  
JEAN-CLAUDE BECKER ◽  
...  

Objective.This article reports 1-year clinical outcomes in the subgroup of patients with rheumatoid arthritis in the Abatacept study to Gauge Remission and joint damage progression in methotrexate-naive patients with Early Erosive rheumatoid arthritis (AGREE) who achieved radiographic nonprogression at the end of the double-blind phase.Methods.Patients who achieved radiographic nonprogression (change from baseline in total Sharp score ≤ 0 at 12 months) with abatacept plus methotrexate (MTX) or MTX alone were eligible for this analysis. Clinical outcomes were remission, defined by 28-joint Disease Activity Score (DAS28) using C-reactive protein (CRP), low Disease Activity Score (LDAS), American College of Rheumatology (ACR) scores, physical function (Health Assessment Questionnaire), and tender and swollen joint counts. Safety was assessed at each visit.Results.Patients in the abatacept plus MTX and MTX monotherapy groups had similar baseline characteristics and were similar to the overall study population. The proportion of patients who achieved DAS28 (CRP) remission or LDAS was greater with abatacept plus MTX vs MTX alone [43.2% vs 22.7% (p < 0.001) and 57.4% vs 40.6% (p = 0.008), respectively]. More patients receiving abatacept plus MTX achieved key ACR responses, including major clinical response (27.3% vs 11.9%; p < 0.001). Safety profiles were similar in both treatment groups.Conclusion.More MTX-naive patients with early RA who achieved radiographic nonprogression taking abatacept plus MTX also achieved DAS28 (CRP)-defined remission and LDAS compared with patients who received MTX alone, supporting the use of abatacept as a first-line biologic in combination with disease-modifying antirheumatic drugs.


2021 ◽  
pp. annrheumdis-2020-219213
Author(s):  
René Westhovens ◽  
William F C Rigby ◽  
Désirée van der Heijde ◽  
Daniel W T Ching ◽  
William Stohl ◽  
...  

ObjectivesTo investigate efficacy and safety of the Janus kinase-1 inhibitor filgotinib in patients with active rheumatoid arthritis (RA) with limited or no prior methotrexate (MTX) exposure.MethodsThis 52-week, phase 3, multicentre, double-blind clinical trial (NCT02886728) evaluated once-daily oral filgotinib in 1252 patients with RA randomised 2:1:1:2 to filgotinib 200 mg with MTX (FIL200 +MTX), filgotinib 100 mg with MTX (FIL100 +MTX), filgotinib 200 mg monotherapy (FIL200), or MTX. The primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 24.ResultsThe primary endpoint was achieved by 81% of patients receiving FIL200+ MTX versus 71% receiving MTX (p<0.001). A significantly greater proportion treated with FIL100+ MTX compared with MTX achieved an ACR20 response (80%, p=0.017) at week 24. Significant improvement in Health Assessment Questionnaire-Disability Index was seen at week 24; least-squares mean change from baseline was −1.0 and −0.94 with FIL200+MTX and FIL100+MTX, respectively, versus −0.81 with MTX (p<0.001, p=0.008, respectively). Significantly higher proportions receiving FIL200+MTX (54%) and FIL100+MTX (43%) achieved DAS28(CRP) <2.6 versus MTX (29%) (p<0.001 for both) at week 24. Hierarchical testing stopped for comparison of ACR20 for FIL200 monotherapy (78%) versus MTX (71%) at week 24 (p=0.058). Adverse event rates through week 52 were comparable between all treatments.ConclusionsFIL200+MTX and FIL100+MTX both significantly improved signs and symptoms and physical function in patients with active RA and limited or no prior MTX exposure; FIL200 monotherapy did not have a superior ACR20 response rate versus MTX. Filgotinib was well tolerated, with acceptable safety compared with MTX.


Lupus ◽  
2016 ◽  
Vol 26 (6) ◽  
pp. 598-605 ◽  
Author(s):  
Y B Joo ◽  
S Won ◽  
C-B Choi ◽  
S-C Bae

Objective The objective of this study was to investigate the association of lupus nephritis on organ damage and mortality in patients with systemic lupus erythematosus (SLE). Methods A total of 1112 patients with SLE were investigated. Lupus nephritis was defined as a proteinuria based on the 1997 American College of Rheumatology criteria. Damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. The associations of lupus nephritis with overall, non-renal, corticosteroid-associated, and non-associated damage were analyzed using logistic regression. The age-adjusted and sex-adjusted standardized mortality ratio was evaluated in patients with and without lupus nephritis. Results The prevalence of lupus nephritis in patients with SLE was 46.3%. Patients with lupus nephritis had a higher percentage of overall cumulative damage than patients without lupus nephritis (51.5% vs. 35.7%, p < 0.001). The odds ratio was 1.40 after adjusting for age at SLE diagnosis, sex, disease duration, anti-malarial agents, immunosuppressive agents and cumulative corticosteroid dose. Among non-renal damage, the odds of corticosteroid-associated damage were higher (2.06, 95% confidence interval (CI) 1.43–2.96) whereas the odds of non-associated damage were lower (0.50, 95% CI 0.35–0.75) in patients with lupus nephritis. The standardized mortality ratios of patients with and without lupus nephritis were 5.17 (95% CI 3.49–7.38) and 2.32 (95% CI 1.47–3.48), respectively. Conclusion In patients with SLE, the presence of lupus nephritis is associated with increased corticosteroid-associated damage but less corticosteroid non-associated damage. Also, mortality is significantly higher in patients with lupus nephritis than in those without lupus nephritis.


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