Wenche Koldingsnes

Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies

Background: The classification of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and polyarteritis nodosa (PAN) for epidemiology studies is confusing. The existing schemes such as American College of Rheumatology (ACR) criteria, Chapel Hill Consensus Conference (CHCC) definitions and Lanham criteria produce overlapping and conflicting classifications, making it difficult to compare incidence figures. Aim: To develop a consensus method of using these criteria and definitions for epidemiological studies to permit comparison without confounding by classification. Methods: A stepwise algorithm was developed by consensus between a group of doctors interested in the epidemiology of vasculitis. The aim was to categorise patients with Wegener’s granulomatosis, microscopic polyangiitis (MPA), Churg–Strauss syndrome (CSS) and PAN into single clinically relevant categories. The ACR and Lanham criteria for CSS, and ACR criteria for Wegener’s granulomatosis were applied first, as these were considered to be the most specific. Surrogate markers for Wegener’s granulomatosis were included to distinguish Wegener’s granulomatosis from MPA. MPA was classified using the CHCC definition and surrogate markers for renal vasculitis. Finally, PAN was classified using the CHCC definition. The algorithm was validated by application to 20 cases from each centre and 99 from a single centre, followed by a paper case exercise. Results: A four-step algorithm was devised. It successfully categorises patients into a single classification. There was good correlation between observers in the paper case exercise (91.5%; unweighted κ = 0.886). Conclusion: The algorithm achieves its aim of reliably classifying patients into a single category. The use of the algorithm in epidemiology studies should permit comparison between geographical areas.

The comparative one‐year performance of anti–tumor necrosis factor α drugs in patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: Results from a longitudinal, observational, multicenter study

OBJECTIVE To compare the 1-year retention rates of anti-tumor necrosis factor alpha (anti-TNFalpha) medications in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) with complementary analyses of the effect on health status. METHODS Our analyses comprised 847, 172, and 249 anti-TNFalpha treatment courses in patients with RA, PsA, and AS, respectively. Crude drug survival was compared and hazard ratios (HRs) for treatment termination were calculated with adjustments for age, sex, investigators global assessment, and concomitant methotrexate (MTX). Adjusted changes in health-related quality of life (HRQOL) were compared among the groups. RESULTS Unadjusted 1-year retention rates were 65.4%, 77.3%, and 77.5% in the RA, PsA, and AS groups, respectively. The adjusted HRs for treatment termination were 0.76 (95% confidence interval [95% CI] 0.53-1.07) for PsA versus RA and 0.66 (95% CI 0.47-0.92) for AS versus RA. High baseline disease activity and female sex were significantly associated with premature treatment termination, whereas concomitant MTX was associated with better drug survival. However, the impact of MTX was apparent for RA and PsA, but not for AS in stratified analyses. The improvements in HRQOL were superior in patients with PsA and AS compared with RA. CONCLUSION Our results suggest that survival of anti-TNFalpha treatment is superior in AS and PsA patients compared with RA patients. Larger improvements in HRQOL in patients with spondylarthritides may contribute to the differences in drug survival. Concomitant MTX was associated with better retention rates in RA and PsA patients, but not AS patients.

Neuropsychiatric disturbances in SLE are associated with antibodies against NMDA receptors

To determine whether neuropsychiatric manifestations in patients with systemic lupus erythematosus (SLE) are influenced by antibodies against the human N‐methyl‐d‐aspartate (NMDA) receptor types NR2a or NR2b. A decapeptide was synthesized containing a sequence motif present in the extracellular ligand‐binding domain of NMDA receptors NR2a and NR2b, bound by the monoclonal murine anti‐DNA antibody R4A. In an ELISA with the murine monoclonal R4v as positive control, plasma samples of 57 patients with SLE were examined for the anti‐peptide (anti‐NR2) antibody after the patients had been subjected to comprehensive psychological and cognitive testing. Poor performance on the Visual Paired Associates test (immediate), the Grooved Pegboard test, as well as high scores on the Beck Depression Inventory, and scales D‐2 (depression), Pd‐4 (psychopathic deviate), Sc‐8 (schizophrenia), and Ma‐9 (hypomania) of the MMPI‐2 were significantly associated with elevated levels of anti‐NR2 antibodies. The findings in several domains indicate an association between anti‐NR2 antibodies and depressed mood in addition to decreased short‐time memory and learning. Antibodies to NMDA receptors thus may represent one of several mechanisms for cerebral dysfunction in patients with SLE.

Epidemiology of Wegener's granulomatosis in northern Norway

OBJECTIVE To determine if changes in the incidence, prevalence, and clinical presentation of Wegeners granulomatosis (WG) have occurred in the stable population of northern Norway during a 15-year period. METHODS We performed a retrospective cohort study using hospital discharge records from all 11 hospitals in the region and the databases of the 2 pathology departments in the area. Only patients fulfilling the American College of Rheumatology 1990 criteria for WG were included in the study, and demographic and clinical data at diagnosis were recorded. Incidence, point prevalence, and period prevalence rates were estimated for three 5-year periods. RESULTS Fifty-five patients (62% male) with a median age at diagnosis of 50 years (range 10-84 years) fulfilled the inclusion criteria. The annual incidence/ million population increased from 5.2 (95% confidence interval [95% CI] 2.7-9.0) during 1984-1988 to 12.0 (95% CI 8.0-17.3) during 1994-1998. The point prevalence/million increased from 30.4 (95% CI 16.6-51.0) to 95.1 (95% CI 69.1-129.0). The highest incidence rate occurred in men ages 65-74 years. There were no significant period differences in age, first organ involved, delay of diagnosis, or disease activity, but fewer patients had malaise and renal insufficiency during the earliest time period. No seasonal variation in the onset of WG was present, although we noted a pattern of annual fluctuation. CONCLUSION The prevalence of WG has tripled in northern Norway over the last 15 years. While more efficacious therapy may explain part of this increase, we also found a significant trend toward increased incidence over that period. The incidence rate over the last 5 years is the highest reported so far, while the clinical presentation has remained unchanged.

Epidemiology of vasculitis in Europe

We recently compared the annual incidence of primary systemic vasculitis (PSV) in two different regions of Europe (Norwich, UK (latitude 52°N) and Lugo, Spain (latitude 43°N)).1Wegeners granulomatosis (WG) was more common in Norwich (10.6/million) than in Spain (4.9/million), though the overall incidence of PSV was similar. This supports the idea that environmental factors may be important in the aetiopathogenesis of PSV. To extend our observations we have now studied the incidence of PSV in northern Europe (Tromso, Norway (latitude 70°N)). …

Effectiveness of switching between TNF inhibitors in ankylosing spondylitis: data from the NOR-DMARD register

Objective To assess the effectiveness of switching to a second tumour necrosis factor inhibitor (TNFi) in patients with ankylosing spondylitis (AS). Methods Data were extracted from an ongoing longitudinal observational multicentre study in Norway. This study included anti-TNF naïve patients with AS starting treatment with a TNFi as well as treatment with a second TNFi in these same patients. Effectiveness data and 2-year drug survival were compared between switchers and non-switchers and within switchers (first and second TNFi). Results 514 anti-TNF naïve patients with AS were included; 77 patients switched to a second TNFi while 437 patients did not switch. The percentages of non-switchers using etanercept, infliximab or adalimumab were 53%, 32% and 15%, and the percentages of first and second TNFi in the switchers were 42%, 53% and 5% and 40%, 23% and 36%, respectively. The reason for switching was insufficient response (IR) in 30, adverse events (AEs) in 44 and not reported in 3 patients. Baseline disease activity was similar between the groups. Three-month BASDAI 50 and ASAS 40 responses were achieved by 49% and 38% of non-switchers, by 25% and 30% of switchers after the first TNFi and by 28% and 31% after the second TNFi. The 3-month disease activity level was higher for switchers on the second TNFi than for non-switchers. Drug withdrawal rate was higher during the second TNFi among switchers than for non-switchers (p=0.001). No difference was found in the effectiveness of the second TNFi between switchers due to IR and AE. Conclusion This study confirms that switching to a second TNFi can be effective in AS and can be as useful as in rheumatoid arthritis, although overall effectiveness seems to be somewhat lower than in non-switchers.

Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow

Abstract Cognitive dysfunction is found in a considerable proportion of patients with systemic lupus erythematosus (SLE). SPECT provides an estimate of regional cerebral blood flow (rCBF) which has been claimed to be sensitive to detect brain involvement in SLE. It is, however, uncertain if these perfusion defects are related to cognitive dysfunction. In the present study we investigated whether cerebral dysfunction assessed by neuropsychological measures was associated with changes in rCBF. Fifty-two SLE patients were examined with a battery of neuropsychological tests and MRI of the brain. For each patient 99mTC-HMPAO-SPECT was performed with the visual cortex as reference, and a reduction in rCBF of > 15 % was considered abnormal. Regional CBF was performed with an automated computer program quantitatively estimating blood perfusion in 16 symmetrical sectors of the brain. Several sectors of the brain showed varying areas of reduced rCBF with the temporal lobes most frequently involved. There were generally no associations between cognitive level of functioning and reduced rCBF. MRI demonstrated cerebral infarcts in 9 (17 %) patients. In general rCBF was reduced in all sectors of the brain in patients with infarcts, although statistical significant difference in rCBF between patients with and without infarcts was only seen in the parietal lobe. Several neuropsychological functions were influenced by the presence of cerebral infarcts. There was no significant association between immunological measures and SPECT findings or neuropsychological measures. Neuropsychological dysfunction in SLE was associated with the presence of cerebral infarcts detected by MRI, but not by changes in rCBF. SPECT seems to add little if any information to that obtained by clinical examination, neuropsychological testing, and MRI. Since anticoagulation may prevent cerebral infarcts, such prophylactic intervention may be of importance in preventing cognitive deterioration.

Effectiveness and retention rates of methotrexate in psoriatic arthritis in comparison with methotrexate-treated patients with rheumatoid arthritis

Objective To examine the effectiveness and 2-year retention rates of methotrexate (MTX) in MTX naïve patients with psoriatic arthritis (PsA). Methods Data on 430 patients with PsA participating in an ongoing longitudinal observational multicentre study in Norway were analysed. 1218 MTX naïve patients with rheumatoid arthritis (RA) from the same study served as a reference population. Assessments included measures of disease activity (28 joint counts, acute phase reactants), health status and utility scores. Six-month effectiveness data were compared both by crude analyses and with adjustments for age, sex and the respective baseline values. Two-year drug survival was compared by Kaplan–Meier and Cox regression analyses. Results After 6 months of MTX treatment, both patients with PsA and those with RA improved in most disease activity measures and patient reported outcomes. In the adjusted analysis, patients with PsA tended to have less improvement, but changes were in the same range as in patients with RA. Two-year retention rates of MTX therapy in patients with PsA and RA were 65% and 66%, respectively, with only minor differences in reported reasons for discontinuation. Lower age, longer disease duration and higher Modified Health Assessment Questionnaire (MHAQ) score and patient global assessment were independent predictors of MTX termination within the first 2 years of treatment. Conclusion In this real-life study, MTX treatment was associated with improvement in disease activity and health-related quality of life in patients with PsA after 6 months of treatment. Retention rates of MTX were similar in PsA and RA.

The comparative effectiveness of anti-TNF therapy and methotrexate in patients with psoriatic arthritis: 6 month results from a longitudinal, observational, multicentre study

Objectives: To compare the response to treatment with tumour necrosis factor (TNF) inhibitors and methotrexate (MTX) monotherapy in patients with psoriatic arthritis (PsA) within a real-life clinical setting. Methods: We analysed data from an ongoing longitudinal, observational multicentre study in Norway. Our data comprised 526 cases of patients with PsA who received either anti-TNF treatment (n = 146) or MTX monotherapy (n = 380) and were followed for at least 6 months with measures of disease activity, health status and utility scores. A propensity score was computed to adjust for channelling bias. The changes in measures of disease activity and health-related quality of life from baseline to 3- and 6-month follow-up were compared between the groups with adjustments for the baseline value of the dependent variable and the propensity score (analyses of covariance (ANCOVA)). Results: The groups were significantly different at baseline with respect to demographic and disease activity measures. The variables included in the propensity score were age, sex, number of previous disease modifying anti-rheumatic drugs (DMARDs), presence of erosive disease, treatment centre and investigator’s global assessment. The adjusted changes at 6 months were significantly larger in the anti-TNF group for ESR, DAS-28, M-HAQ, patient’s assessments of pain, fatigue and global disease activity on a visual analogue scale (VAS) and 4 out of 8 SF-36 dimensions. Conclusions: Clinical improvement was superior with TNF inhibitors compared to MTX monotherapy in patients with PsA, when assessed in this setting of daily clinical practice.

Work disability and health-related quality of life in males and females with psoriatic arthritis

Objectives: To compare health status, demographic variables and work disability (WD) between males and females with psoriatic arthritis (PsA) in the 18–45 age group, and further to compare health status between those with and without WD for each gender and to identify variables associated with WD. Methods: A cross-sectional study was carried out of patients with PsA with peripheral arthritis at the time at which they started disease-modifying antirheumatic drug therapy (DMARD) and/or biological treatment. Patients receiving a permanent national WD pension corresponding to ⩾50% were defined as work disabled. Gender differences were examined with regard to health status, demographic variables and WD. Mann–Whitney U test and Pearson χ2 were applied for group comparisons between males and females and work disabled versus not work disabled for each gender. Multiple logistic regression analyses with adjustments for duration of education, disease duration, age, erosive disease, disability score (Modified Health Assessment Questionnaire; MHAQ), the short form-36 (SF-36) mental health score, and gender were used to identify variables associated with WD. Results: Out of 271 (102 females) patients, the number (%) of work-disabled females/males was 33 (32.7%)/29 (17.4%) (p = 0.004). Work-disabled patients had generally worse health status than non-work-disabled patients, and these differences were generally more pronounced in males than in females. In the multiple logistic regression model, low educational level, increasing disability score (MHAQ), presence of erosive disease, female gender and disease duration were independently associated with WD. Conclusions: WD in patients with PsA below 45 years of age was independently associated with educational level, disability score, erosive disease, female gender and disease duration.