| 1. |
- de Rooy, D. P. C., et al.
(author)
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Smoking as a risk factor for the radiological severity of rheumatoid arthritis: a study on six cohorts
- 2014
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 73:7, s. 1384-1387
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Journal article (peer-reviewed)abstract
- Background Smoking is a risk factor for the development of anti -citrullinated protein antibodies (ACPA) positive rheumatoid arthritis (RA). Whether smoking predisposes to severe joint damage progression is not known, since deleterious, protective and neutral observations have been made. Objective To determine the effect of smoking on joint damage progression. Methods Smoking status was assessed in 3158 RA patients included in six cohorts (Leiden Early Arthritis Clinic (Leiden-EAC), BARFOT, Lund, Iceland, NDB and Wichita). In total 9412 radiographs were assessed. Multivariate normal regression and linear regression analyses were performed. Data were summarised in a random effects inverse variance meta-analysis. Results When comparing radiological progression for RA patients that were never, past and current smokers, smoking was significantly associated with more severe joint damage in Leiden-EAC (p=0.042) and BARFOT (p=0.015) RA patients. No significant associations were found in the other cohorts, though a meta-analysis on the six cohorts showed significantly more severe joint damage progression in smokers (p=0.01). Since smoking predisposes to ACPA, analyses were repeated with ACPA as additional adjustment factor. Then the association was lost (meta-analysis p=0.29). Conclusions This multi-cohort study indicated that the effect of smoking on joint damage is mediated via ACPA and that smoking is not an independent risk factor for radiological progression in RA.
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| 2. |
- Bengtsson, Camilla, et al.
(author)
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Common vaccinations among adults do not increase the risk of developing rheumatoid arthritis: results from the Swedish EIRA study
- 2010
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In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 69:10, s. 1831-1833
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Journal article (peer-reviewed)abstract
- Objective To investigate the association between vaccinations in adults and the risk of developing rheumatoid arthritis (RA). Methods Data from the Swedish population-based Epidemiological Investigation of RA case-control study encompassing 1998 incident cases of RA aged 18-70 years and 2252 randomly selected controls matched for age, sex and residency were analysed. Those vaccinated within 5 years before disease onset were compared with those not vaccinated by calculating OR with 95% CI. Results Vaccinations neither increased the risk of RA overall (OR 1.0, 95% CI 0.9 to 1.1) nor the risk of two major subgroups of RA (antibodies to citrullinated peptide-positive (ACPA-positive) and ACPA-negative disease). Furthermore, vaccinations did not increase the risk of RA in smokers or carriers of HLA-DRB1 shared epitope alleles, two groups with established risk factors for RA. Conclusions In this case-control study of incident cases of newly diagnosed RA, no increased risk of RA following immunisation was observed for vaccinations overall or for any specific vaccination. This indicates that immunological provocation of adults with commonly used vaccines in their present form carries no risk of RA. These findings should be implemented among public healthcare providers in order to encourage vaccinations according to recommended national vaccination schedules.
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| 3. |
- C Kapetanovic, Meliha, et al.
(author)
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Antibody response is reduced following vaccination with 7-valent conjugate pneumococcal vaccine in adult methotrexate-treated patients with established arthritis, but not those treated with tumor necrosis factor inhibitors
- 2011
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In: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 63:12, s. 3723-3732
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Journal article (peer-reviewed)abstract
- Objective To study the influence of antiinflammatory treatments, including methotrexate (MTX) and tumor necrosis factor (TNF) inhibitors, on antibody response following vaccination using a 7-valent conjugate pneumococcal vaccine in adult patients with established arthritis. Methods. Patients with rheumatoid arthritis (RA) or spondylarthropathy (SpA) (including psoriatic arthritis) were vaccinated (n = 505). All patients were stratified into 6 prespecified groups based on diagnosis and treatment (RA patients receiving MTX, RA patients receiving anti-TNF agents and MTX, RA patients receiving TNF inhibitors as monotherapy, SpA patients receiving anti-TNF agents and MTX, SpA patients receiving TNF inhibitors as monotherapy, and SpA patients receiving nonsteroidal antiinflammatory drugs [NSAIDs] and/or analgesics). SpA patients receiving only NSAIDs/analgesics served as a control group. All patients received 1 dose (0.5 ml) of vaccine intramuscu-larly. Levels of IgG antibodies against 23F and 6B serotypes were measured at vaccination and at 4-6 weeks following vaccination, using standardized enzyme-linked immunosorbent assays. Results. Positive antibody response was defined as an antibody response ratio (ARR) (i. e., ratio of post-to prevaccination antibody levels) of > 2. The ARR differed significantly between the groups. A better ARR was seen among patients in the control group compared to those in groups treated with MTX or MTX in combination with TNF inhibitors. Among patients treated with TNF inhibitors as monotherapy, ARRs for both serotypes were lower numerically, but were not significantly different, compared to those in controls. Ongoing MTX treatment was predictive of reduced response (odds ratio 0.41 [95% confidence interval 0.24-0.68], P = 0.001). Higher age was associated with impaired positive antibody response. Concomitant prednisolone treatment elicited better positive antibody response in patients with RA. Conclusion. Treatment with MTX and higher age were predictive of an impaired antibody response to the 7-valent conjugate pneumococcal vaccine in this cohort of patients with chronic arthritis. TNF inhibitors did not significantly affect antibody responses.
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| 4. |
- C Kapetanovic, Meliha, et al.
(author)
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Early changes in bone mineral density measured by digital X-ray radiogrammetry predict up to 20 years radiological outcome in rheumatoid arthritis.
- 2011
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In: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362. ; 13:1
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Journal article (peer-reviewed)abstract
- ABSTRACT: INTRODUCTION: Change in bone mineral density (BMD) in the hand, as evaluated by digital X-ray radiogrammetry (DXR) of the II-IV metacarpal bones, has been suggested to predict future joint damage in rheumatoid arthritis (RA). This study's objective was to investigate if DXR-BMD loss early in the disease predicts development of joint damage in RA patients followed for up to 20 years. METHODS: 183 patients (115 women and 68 men) with early RA (mean disease duration 11 months) included from 1985 to 1989 were followed prospectively (the Lund early RA cohort). Clinical and functional measures were assessed yearly. Joint damage was evaluated according to the Larsen score on radiographs of hands and feet taken in years 0 to 5, 10, 15 and 20. These radiographs were digitized and BMD of the II-IV metacarpal bones was evaluated by DXR (Sectra, Linkoping. Sweden). Early DXR-BMD change rate (bone loss) per year calculated from the first 2 radiographs taken on average 9 months apart (SD 4.8) were available for 135 patients. Mean values of right and left hand were used. RESULTS: Mean early DXR-BMD loss during the first year calculated was -0.023 g/cm2 (SD 0.025). Patients with marked bone loss, i.e. early DXR-BMD loss above the median for the group, had significantly worse progression of joint damage at all examinations during the 20-year period. CONCLUSIONS: Early DXR-BMD progression rate predicted development of joint damage evaluated according to Larsen at year one and further onwards up to 20 years in this cohort of early RA patients.
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| 5. |
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| 6. |
- C Kapetanovic, Meliha, et al.
(author)
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Heptavalent pneumococcal conjugate vaccine elicits similar antibody response as standard 23-valent polysaccharide vaccine in adult patients with RA treated with immunomodulating drugs.
- 2011
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In: Clinical Rheumatology. - : Springer Science and Business Media LLC. - 1434-9949 .- 0770-3198. ; 30:12, s. 1555-1561
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Journal article (peer-reviewed)abstract
- The objectives of the study were to compare antibody response in immunosuppressed patients with rheumatoid arthritis (RA) after vaccination with heptavalent pneumococcal conjugate vaccine (PCV7) to that of RA patients and healthy controls vaccinated with 23-valent polysaccharide vaccine (PPV23) and to study the impact of disease and/or treatment characteristics and type of vaccine on antibody response following pneumococcal vaccination in patients with RA. In total, 253 RA patients treated with methotrexate (MTX), anti-TNF blockers as monotherapy or anti-TNF + MTX were vaccinated with a single dose (0.5 ml) of PCV7. In addition, 149 RA patients receiving corresponding treatments and 47 healthy controls were vaccinated with a single dose (0.5 ml) of PPV23. Serotype-specific IgG to 23F and 6B were measured at vaccination and 4-6 weeks after vaccination using ELISA. Antibody response ratio (ARR), i.e. ratio between post-/prevaccination antibody levels, was compared between corresponding treatment groups. Differences in ARR were analysed using analysis of variance. Positive antibody response (posAR) was defined as equal to or greater than twofold increase in prevaccination antibody levels. Possible predictors of posAR were analysed using logistic regression model. Corresponding RA treatment groups showed similar ARR and posAR for both serotypes regardless of vaccine type. Higher age at vaccination and concomitant MTX were identified as predictors of impaired posAR for both serotypes tested, whereas type of vaccine did not influence posAR significantly. PCV7 elicits similar antibody response as PPV23 in patients with RA receiving immunosuppressive treatment. In RA patients, higher age and MTX treatment but not type of vaccine predicted impaired posAR.
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| 7. |
- C Kapetanovic, Meliha, et al.
(author)
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Impact of anti-rheumatic treatment on immunogenicity of pandemic H1N1 influenza vaccine in patients with arthritis.
- 2014
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In: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 16:1
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Journal article (peer-reviewed)abstract
- An adjuvanted pandemic H1N1 influenza (pH1N1) vaccine (Pandemrix®) was reported as highly immunogenic resulting in seroconversion in 77 to 94% of adults after administration of a single dose. The aim of the study was to investigate the impact of different anti-rheumatic treatments on antibody response to pH1N1 vaccination in patients with rheumatoid arthritis (RA) and spondylarthropathy (SpA).
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| 8. |
- C Kapetanovic, Meliha, et al.
(author)
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Long-term mortality rate in rheumatoid arthritis patients with disease onset in the 1980s.
- 2011
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In: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 40, s. 433-438
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Journal article (peer-reviewed)abstract
- Objective: To investigate the mortality rate and possible early predictive factors of mortality after 19-23 years in a cohort of patients with rheumatoid arthritis (RA) followed prospectively from disease onset. Patients and methods: A community-based cohort of 183 patients (63% female) with RA and disease duration < 2 years was recruited 1985-1989. The patients were followed yearly from diagnosis until death or 31 December 2008. Mean age and mean duration of symptoms (range) at diagnosis were 52 (18-78) years and 11 (0-24) months, respectively. Death certificates were obtained from the Swedish Cause of Death Register and causes of death were coded by the International Classification of Diseases (ICD-10). Death rates of RA patients were compared to those of age- and sex-matched controls. Possible predictors of mortality were analysed using a Cox regression model. Results: By 31 December 2008, 69 patients (37 women and 32 men) had died. The standardized mortality ratio (SMR) was 1.23 [95% confidence interval (CI) 0.97-1.55] and p < 0.09. Older age, male sex, smoking, and the presence of cardiovascular disease (CVD) at RA diagnosis were identified as early predictors of mortality. CVD was the most common cause of death (46%), followed by malignancies (29%) and infections (13%). RA was not stated as the direct cause of death in any patient and was mentioned among underlying causes in only 16/69 (23%) patients. Conclusion: Mortality rate after 19-23 years of disease duration in this cohort of patients with disease onset in the 1980s was not significantly increased compared to age- and sex-matched controls. No RA disease-related factor predicted mortality.
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| 9. |
- C Kapetanovic, Meliha, et al.
(author)
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Persistence of antibody response 1.5 years after vaccination using 7-valent pneumococcal conjugate vaccine in patients with arthritis treated with different antirheumatic drugs
- 2013
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In: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 15:1
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Journal article (peer-reviewed)abstract
- Introduction: The aim of this study was to explore the persistence of an antibody response 1.5 years after vaccination with 7-valent pneumococcal conjugate vaccine in patients with rheumatoid arthritis (RA) or spondyloarthropathy (SpA) treated with different antirheumatic drugs. Methods: Of 505 patients initially recruited, data on current antirheumatic treatment and blood samples were obtained from 398 (79%) subjects after mean (SD, range) 1.4 (0.5; 1 to 2) years. Antibody levels against pneumococcal serotypes 23F and 6B were analyzed by using enzyme-linked immunosorbent assay (ELISA). Original treatment groups were as follows: (a) RA receiving methotrexate (MTX); (b) RA taking anti-TNF monotherapy; (c) RA taking anti-TNF+MTX; (d) SpA with anti-TNF monotherapy; (e) SpA taking anti-TNF+MTX; and (f) SpA taking NSAID/analgesics. Geometric mean levels (GMLs; 95% CI) and proportion (percentage) of patients with putative protective antibody levels >= 1 mg/L for both serotypes, calculated in different treatment groups, were compared with results 4 to 6 weeks after vaccination. Patients remaining on initial treatment were included in the analysis. Possible predictors of persistence of protective antibody response were analysed by using logistic regression analysis. Results: Of 398 patients participating in the 1.5-year follow up, 302 patients (RA, 163, and SpA, 139) had unchanged medication. Compared with postvaccination levels at 1.5 years, GMLs for each serotype were significantly lower in all groups (P between 0.035 and <0.001; paired-sample t test), as were the proportions of patients with protective antibody levels for both serotypes (P < 0.001; chi(2) test). Higher prevaccination antibody levels for both serotypes 23F and 6B were associated with better persistence of protective antibodies (P < 0.001). Compared with patients with protective antibody levels at 1.5 years, those not having protective antibody levels were older, more often women, had longer disease duration and higher HAQ and DAS, and had a lower proportion of initial responders to both serotypes. Concomitant anti-TNF treatment and MTX were identified as negative predictors of the persistence of protective antibodies among RA patients (P = 0.024 and P = 0.065, respectively). Only age 65 years or older (P = 0.017) and not antirheumatic treatment was found to be a negative predictor of protective antibodies in patients with SpA. Conclusions: After initial increase, 1.5 years after pneumococcal vaccination with 7-valent conjugate vaccine, postvaccination antibody levels decreased significantly, reaching levels before vaccination in this cohort of patients with established arthritis treated with different antirheumatic drugs. MTX and anti-TNF treatment predicted low persistence of protective immunity among patients with RA. To boost antibody response, early revaccination with conjugate vaccine might be needed in patients receiving potent immunosuppressive remedies.
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| 10. |
- C Kapetanovic, Meliha, et al.
(author)
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Prevalence and predictive factors of comorbidity in rheumatoid arthritis patients monitored prospectively from disease onset up to 20 years: lack of association between inflammation and cardiovascular disease.
- 2010
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In: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 39, s. 353-359
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Journal article (peer-reviewed)abstract
- Objectives: To study the prevalence of comorbid conditions at diagnosis and during follow-up in a cohort of patients with early rheumatoid arthritis (RA) followed prospectively over 20 years, and to identify possible early predictive factors for future comorbidities. Methods: A community-based cohort of 183 patients (mean age 52 years, 63% female) with early RA was recruited between 1985 and 1989. The presence of comorbidity at RA diagnosis and the occurrence of additional comorbidities were recorded continuously. Possible predictors of future comorbidities were analysed using the Cox proportional hazards model. Results: At RA diagnosis, at least one comorbid condition was present in 43% of the patients. Cardiovascular diseases (CVDs), including hypertension (16% of patients) and malignancy (6% of patients), were most common. In total, 82% of patients developed additional comorbidities during follow-up. CVD and malignancies remained the most frequent comorbidities. Higher age [p < 0.001, odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01-1.15] and the presence of any comorbidity at diagnosis (p = 0.02; OR 1.64, 95% CI 1.08-2.52) predicted future comorbidity. Measures of inflammation at diagnosis or during follow-up were not predictive for development of CVD. Conclusion: Comorbidity was present in a considerable proportion of patients in this cohort. More than 40% of patients had another disease at inclusion and during follow-up and > 80% developed additional conditions. The pattern of comorbidity remained unchanged, with CVD and malignancy being most common. Older age and the presence of comorbidity at RA diagnosis predicted the development of comorbidities. The degree of inflammation at any time point was not predictive of future CVD.
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