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.

Effectiveness of adalimumab in treating patients with active psoriatic arthritis and predictors of good clinical responses for arthritis, skin and nail lesions.

OBJECTIVES: To evaluate the effectiveness of adalimumab in patients with psoriatic arthritis (PsA) and identify predictors of good clinical response for joint and skin lesions. METHODS: Patients received adalimumab 40 mg every other week in addition to standard therapy in this prospective, 12-week, open-label, uncontrolled study. Four definitions of good clinical response were used: > or =50% improvement in American College of Rheumatology response criteria (ACR50), good response according to European League Against Rheumatism (EULAR) guidelines, a > or =3-grade improvement in Physician Global Assessment of psoriasis (PGA) and a > or =50% improvement in the Nail Psoriasis Severity Index (NAPSI). Response predictors were determined by logistic regression with backward elimination (selection level was 5%). RESULTS: Of 442 patients, 94% completed 12 weeks of treatment. At week 12, 74%, 51% and 32% of the patients had achieved ACR20, 50 and 70, respectively; 87% and 61% experienced moderate and good responses according to EULAR criteria, respectively. The percentage of patients with PGA results of "clear/almost clear" increased from 34% (baseline) to 68%. The mean NAPSI score was reduced by 44%. No new safety signals were detected. A lower Health Assessment Questionnaire Disability Index (HAQ-DI) score, greater pain assessment, male sex and absence of systemic glucocorticoid therapy were strongly associated with achievement of ACR50 and good response according to EULAR criteria. In addition, greater C-reactive protein concentration and polyarthritis predicted ACR50, and non-involvement of large joints predicted a good response according to EULAR criteria. CONCLUSIONS: Adalimumab was effective in patients with PsA. Lower impairment of physical function, greater pain, male sex and no systemic treatment with glucocorticoids were factors that increased the chance of achieving a good clinical response.

Contemporary use of disease-modifying drugs in the management of patients with early rheumatoid arthritis in Norway.

OBJECTIVE: As treatment options for rheumatoid arthritis (RA) are rapidly expanding, we evaluated the current use of disease-modifying anti-rheumatic drugs (DMARDs) in the management of patients with early RA in Norway with particular attention to the influence of risk factors for a poor disease outcome on DMARD selection. METHODS: An observational multicentre study registering the type of therapy initiated in 820 DMARD-naive patients with early active RA [67% female, mean age 51 years, disease duration 4 months, 57% rheumatoid factor (RF) positive]. The impact of baseline risk factors associated with poor prognosis (disease activity parameters and biomarkers of inflammation) on DMARD selection was analysed through odds ratios (ORs) by multivariate logistic regression. RESULTS: Methotrexate (MTX) monotherapy was selected for 78% of patients. MTX was preferred over sulfasalazine (SSZ) monotherapy (19%), leflunomide monotherapy (2%), and combination therapy (2%) in female patients [OR 1.6, 95% confidence interval (CI) 1.1-2.5], age >50 years (OR 2.5, 95% CI 1.6-3.8), short disease duration (OR 2.7, 95% CI 1.4-5.0), 10 swollen joints (OR 2.2, 95% CI 1.2-4.0), and erosive disease (OR 1.8, 95% CI 1.1-3.2). Concurrent steroid therapy was started in 73% of patients, regardless of the type of DMARD therapy initiated. CONCLUSION: Monotherapy with MTX is currently the DMARD treatment of choice for early RA in Norway. Disease duration, age, swollen joint count, and erosive disease have considerable impact on DMARD selection in contrast to the presence of biomarkers. Few patients with early RA in Norway receive combination DMARD therapy, while the majority of patients receive corticosteroid bridging therapy.

A novel mutation in the NOD2 gene associated with Blau syndrome: a Norwegian family with four affected members.

BACKGROUND: Blau syndrome is a chronic granulomatous disease with an autosomal dominant trait characterized by the triad granulomatous dermatitis, arthritis, and uveitis. It is caused by mutations in the NOD2 gene, also termed the CARD15 gene. OBJECTIVE: To report a novel mutation in the NOD2 gene associated with Blau syndrome. METHODS AND RESULTS: The proband was a 68-year-old ethnic Norwegian male who had uveitis and arthritis since 10 years of age followed by lifelong recurrent arthritis and chronic eye involvement. Genetic analysis showed a heterozygous c.1814 C>A, T605N mutation in NOD2 that has not previously been described. All of his three children had Blau syndrome and had inherited the NOD2 mutation. The proband's first son had exanthema, arthritis, and uveitis from 10 years of age and later presented with granulomatous lymphadenopathy, granulomatous parotitis, and granulomatous intestinal inflammation. The proband's daughter had arthritis, uveitis, and exanthema from 3 years of age. The proband's second son had uveitis, exanthema, and arthritis from 1.5 years of age. None of the cases had any involvement of the heart or lungs. CONCLUSION: We report a novel Blau syndrome-associated mutation with an autosomal dominant heritage. Most likely the mutation has arisen de novo in the proband. Genetic counselling and antenatal diagnostics should be available to the involved families.

Adalimumab effectively reduces the rate of anterior uveitis flares in patients with active ankylosing spondylitis: results of a prospective open-label study.

OBJECTIVE: To evaluate the effect of adalimumab on the frequency of anterior uveitis (AU) flares in patients with active ankylosing spondylitis (AS). METHODS: We determined the history of ophthalmologist-diagnosed AU in 1250 patients with active AS who were enrolled in a multinational, open-label, uncontrolled clinical study of treatment with adalimumab, 40 mg every other week for up to 20 weeks. All AU flares were documented throughout the adalimumab treatment period plus 70 days. We compared the rates of AU flares per 100 patient years (PYs) reported during the year before adalimumab treatment with rates during adalimumab treatment, in total and by patient subgroups. RESULTS: The AU flare rates before adalimumab treatment were 15/100 PYs in all patients (n = 1250), 68.4/100 PYs in 274 patients with a history of AU flares, 176.9/100 PYs in 106 patients with a recent history of AU flares, 192.9/100 PYs in 28 patients with symptomatic AU at baseline and 129.1/100 PYs in 43 patients with a history of chronic uveitis. During adalimumab treatment, the rate of AU flares was reduced by 51% in all patients, by 58% in 274 patients with a history of AU, by 68% in 106 patients with a recent history of AU, by 50% in 28 patients with symptomatic AU at baseline and by 45% in 43 patients with chronic uveitis. AU flares during adalimumab treatment were predominantly mild. Two patients with periods of high AS disease activity had new-onset AU during the treatment period. CONCLUSIONS: Results of this prospective open-label study suggest that adalimumab had a substantial preventive effect on AU flares in patients with active AS, including patients with a recent history of AU flares. Clinical trials: ClinicalTrials.gov Identifier: NCT00478660.

Comparison of work disability and health-related quality of life between males and females with rheumatoid arthritis below the age of 45 years.

OBJECTIVES: To compare work disability (WD) and health status between males and females with rheumatoid arthritis (RA) in the age group 18-45 years, and to compare health status between patients with and without WD within each gender, and finally to identify factors independently associated with WD in this age group. METHODS: A cross-sectional study of RA patients at the time starting with disease-modifying antirheumatic drug (DMARD) therapy and/or biological treatment. Patients receiving a permanent, national WD pension corresponding to >or= 50% were defined as work disabled. We examined gender differences with regard to disease characteristics, health status and WD. The Mann-Whitney U-test and Pearson's chi(2)-test were applied for group comparisons. Multiple logistic regression analyses with adjustments for duration of education, disease duration, age, erosive disease, disability score [using the Modified Health Assessment Questionnaire (MHAQ)], Disease Activity Score-28 (DAS-28), the Short Form Health Survey (SF-36) mental health score and gender were used to identify variables associated with WD. RESULTS: Out of 474 (372 females) patients, the number (%) of work-disabled females/males was 91 (24.7)/8 (8.1) (p<0.001). WD was associated with worse health status in both genders. The odds ratio (95% confidence interval) [OR (95% CI)] for WD in females vs. males was 4.84 (1.85-12.65) in the multivariate analyses. Other factors independently associated with WD were worse mental health, disease duration and low level of education. CONCLUSION: Females with RA had a fourfold increased risk of WD compared to men. Low level of education, disease duration and worse mental health were also independently associated with WD.

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 >or=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 chi(2) 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.

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.

Adalimumab and methotrexate is more effective than adalimumab alone in patients with established rheumatoid arthritis: results from a 6-month longitudinal, observational, multicentre study.

OBJECTIVES: To compare the effectiveness of adalimumab monotherapy and adalimumab and methotrexate (MTX) combination therapy in patients with established rheumatoid arthritis. METHODS: Data from an ongoing longitudinal observational study in Norway were used to compare response to treatment with two different adalimumab regimens (monotherapy, n = 84; combination with MTX, n = 99). Patients were assessed with measures of disease activity, health status and utility scores. Within-group changes were analysed from baseline to follow-up at 3 and 6 months and the changes were compared between groups after adjustment for the propensity score. The groups were also compared for the proportions of patients achieving European League Against Rheumatism (EULAR) good response, Disease Activity Score (DAS)28 remission and treatment terminations. RESULTS: The improvement from baseline was significant for all measures in the adalimumab and MTX group, but only for DAS28, joint counts, two Short-form Health Survey with 36 questions (SF-36) dimensions and patient's and investigator's global assessment in the monotherapy group. All between-group differences were numerically in favour of combination therapy and significant for C reactive protein, joint counts, DAS28, Modified Health Assessment Questionnaire, investigator's global assessment, four SF-36 dimensions and Short Form 6D at 6 months. More patients in the combination therapy group reached EULAR good response (p<0.001) and remission (p = 0.07). At 6 months, 80.8% of the patients in the combination therapy group and 59.5% in the monotherapy group remained on treatment (p = 0.002). More withdrawals in the monotherapy group were due to adverse events. CONCLUSIONS: Our results were consistent across several categories of end points and suggest that adalimumab combined with MTX is effective in patients with rheumatoid arthritis treated in daily clinical practice and is superior to adalimumab monotherapy.

A Norwegian DMARD register: prescriptions of DMARDs and biological agents to patients with inflammatory rheumatic diseases.

Information concerning the effectiveness of drug therapy cannot be obtained only from randomized controlled clinical trials, due to limitations such as a short time frame and narrow inclusion and exclusion criteria. Therefore, complementary longitudinal observational studies performed in a real life setting are required. NOR-DMARD, a Norwegian 5-center register, was established in December 2000. All DMARD prescriptions to patients with inflammatory arthropathies are included, and patients are followed longitudinally with a variety of assessments. As of 2005, 4683 DMARD regimens have been included. Methotrexate is the most commonly used DMARD in rheumatoid arthritis and psoriatic arthritis. The proportions of patients who have received anti-TNF drugs in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, juvenile arthritis and other diseases have been 22.5, 21.6, 53.8, 36.9 and 9.7%, respectively. The proportion of patients receiving anti-TNF drugs is considerably higher in 2004 than earlier, and criteria for prescribing anti-TNF drugs appear to be trending toward patients with less severe and active disease. Confounding by indication or channeling bias represents a challenge for the group comparisons of longitudinal effectiveness data, but can be addressed by modern statistical techniques. The NOR-DMARD register may in the future provide comparative real life effectiveness data that may also be used in cost-effectiveness analyses.

[Takayasu's arteritis]. / Takayasus arteritt.

BACKGROUND: Takayasu's arteritis is a chronic, idiopathic, inflammatory disease that affects aorta and its main branches. The disease is rare; its etiology is unknown and shows race differences. The inflammation of the arteries may lead to stenosis, occlusions, dilatations or aneurysms. The clinical picture and angiographic findings are not previously reported in a Norwegian cohort. MATERIAL AND METHODS: We report a retrospective, hospital-based study describing the clinical picture, diagnostic findings, treatment and prognosis in a cohort of six patients in Central Norway with Takayasu's arteritis. The data was extracted through chart review. RESULTS: In the period 1988-2000, six patients with Takayasu's arteritis, five women and one man, were identified. All the patients were of Norwegian origin. Median age at diagnosis was 39 years, range 24-63 years, and median time from first symptoms to definite diagnosis was six months, range 1-36 months. The estimated minimum annual incidence was 0.8 per million. All patients had elevated erythrocyte sedimentation rate; five out of six patients had unilateral or bilateral subclavian stenosis; one patient had a thoracoabdominal aneurysm. All patients were treated with prednisolone. There were no deaths in the observation period of median 7.5 years, range 0-26 years. INTERPRETATION: Takayasu's arteritis is a rare disease in our region, with lower incidence than reported in the literature. The prognosis is excellent, but the morbidity was substantial. The clinical findings are similar to those reported in other studies. The location and appearance of the angiographic findings were characteristic for the disease.

[Leflunomide--a new disease modifying anti-rheumatic agent]. / Leflunomid--et nytt sykdomsmodifiserende antirevmatisk legemiddel.

BACKGROUND: Leflunomide is a novel disease-modifying antirheumatic drug (DMARD) for treatment of rheumatoid arthritis. The agent has been developed for the treatment of rheumatoid arthritis, but its multiple immunomodulatory properties may in the future be of interest in the treatment of other rheumatic and immunological diseases. MATERIAL AND METHODS: Review of the literature in order to present the current relevant clinical documentation of the drug. RESULTS: The clinical documentation is mainly based on three large, prospective, randomized trials of six months "to two years" duration comparing leflunomide with placebo, sulphasalazine or methotrexate. The efficacy of leflunomide in all trials was superior to placebo and comparable to sulphasalazine and methotrexate. The frequency of adverse events was also comparable to the comparators. INTERPRETATION: Leflunomide is a safe and efficacious addition to the roster of antirheumatic drugs, but further clinical trials and experience from clinical practice are needed in the evaluation of its place as a disease-modifying agent.

[Polychondritis--a rare and difficult diagnosis]. / Polykondritt--en vanskelig og sjelden diagnose.

We present two patients with polychondritis. Polychondritis is a rare inflammatory disease of unknown origin, but immunological mechanisms are essential in the pathogenesis. Histological features are inflammation and destruction of cartilage. The disease is systemic, may have a remitting course, and it can be primary or associated with several other diseases. We also review the literature with emphasis on symptoms, clinical presentation, diagnostic procedures and treatment. The literature consists mainly of case reports, summary of case reports, no epidemiological and only few clinical studies. Two sets of diagnostic criteria with great similarities have been proposed. Non-steroidal antiinflammatory drugs or immunosuppressive drugs like glucocorticoids and cyclophosphamide are the drugs of choice, depending on the stage and severity of the disease.

[Rheumatoid arthritis and heart disease]. / Reumatoid artritt og hjertesykdom.

Rheumatoid arthritis is a chronic inflammatory disease that usually involves the joints, tendons and bursae. The disease is systemic and may involve the brain, peripheral nerves, lungs, kidneys, heart and blood-vessels. All anatomical structures of the heart may be involved. Most reports on rheumatoid arthritis and heart disease are case reports and autopsy studies. Sonography studies from recent years show pathology in some heart structures at about the same rate as autopsy studies. Mortality studies from the last ten years provide evidence of increased cardiovascular mortality. The frequency of reported rheumatoid heart disease differs according to the method applied in the studies. Clinically significant disease is infrequent. We describe two cases with pericarditis and give a review of the literature.

[Systemic sclerosis. A diagnostic and follow-up program]. / Systemisk sklerose. Et utrednings--og kontrollprogram.

Systemic sclerosis (scleroderma) is a rare chronic progressive multiorgan disease characterized by elevated collagen content in affected organs. The condition is classified in the group connective tissue diseases, and appears in both a systemic and a limited form. The rate of progression and the prognosis differ for the two forms. The heterogeneity of the disease makes systematic examination of the patients necessary in order to provide a correct diagnosis and classification as a basis for therapy and prognosis. Based on the low incidence and prevalence of the disease, the care of these patients should be a specialist task. At our department, a programme has been introduced consisting of clinical examination, immunological and biochemical analysis, histological examination and different imaging techniques, and with an interdisciplinary approach. This programme has made the management of these patients more standardized.

[Arthritis after BCG treatment of bladder cancer. A rare complication]. / Artritt etter BCG-behandling av blaerekreft. En sjelden komplikasjon.

Since 1976 intravesical instillation of bacillus Calmette-Guerin (BCG) has been used after surgical treatment of bladder cancer. Local side effects like cystitis are common, but a small share of the patients develop influenza-like symptoms, arthritis and other complications. We describe two patients with arthritis.