Patient-reported outcomes in axial spondyloarthritis and psoriatic arthritis patients treated with secukinumab for 24 months in daily clinical practice.

OBJECTIVES: In patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) initiating secukinumab, we aimed to assess and compare the proportion of patients achieving 6-, 12- and 24-month patient-reported outcomes (PRO) remission and the 24-month retention rates. PATIENTS AND METHODS: Patients with axSpA or PsA from 16 European registries, who initiated secukinumab in routine care were included. PRO remission rates were defined as pain, fatigue, Patient Global Assessment (PGA) ≤2 (Numeric Rating Scale (NRS) 0-10) and Health Assessment Questionnaire (HAQ) ≤0.5, for both axSpA and PsA, and were calculated as crude values and adjusted for drug adherence (LUNDEX). Comparisons of axSpA and PsA remission rates were performed using logistic regression analyses (unadjusted and adjusted for multiple confounders). Kaplan-Meier plots with log-rank test and Cox regression analyses were conducted to assess and compare secukinumab retention rates. RESULTS: We included 3087 axSpA and 3246 PsA patients initiating secukinumab. Crude pain, fatigue, PGA and HAQ remission rates were higher in axSpA than in PsA patients, whereas LUNDEX-adjusted remission rates were similar. No differences were found between the patient groups after adjustment for confounders. The 24-month retention rates were similar in axSpA vs. PsA in fully adjusted analyses (HR [95 %CI] = 0.92 [0.84-1.02]). CONCLUSION: In this large European real-world study of axSpA and PsA patients treated with secukinumab, we demonstrate for the first time a comparable effectiveness in PRO remission and treatment retention rates between these two conditions when adjusted for confounders.

Course and predictors of work productivity in gout - results from the NOR-Gout longitudinal 2-year treat-to-target study.

OBJECTIVES: In patients with gout there is a lack of longitudinal studies on the course of work productivity. We explored longitudinal changes in and predictors of work productivity over 2 years. METHODS: Patients in the NOR-Gout observational study with a recent gout flare and serum urate (sUA) >360 µmol/l attended tight-control visits during escalating urate lowering therapy according to a treat-to-target strategy. From the Work Productivity and Activity Impairment (WPAI) questionnaire, scores for work productivity and activity impairment were assessed over 2 years together with the Beliefs about Medicines Questionnaire and a variety of demographic and clinical variables. RESULTS: At baseline patients had a mean age of 56.4 years and 95% were males. WPAI scores at baseline were 5.0% work missed (absenteeism), 19.1% work impairment (presenteeism), 21.4% overall work impairment and 32.1% activity impairment. Work productivity and activity impairment improved during the first months, and remained stable at 1 and 2 years. Comorbidities were not cross-sectionally associated with WPAI scores at baseline, but predicted worse work impairment and activity impairment at year 1. The Beliefs about Medicines Questionnaire subscale with concerns about medicines at baseline independently predicted worse overall work impairment and worse activity impairment at year 1. CONCLUSIONS: In patients with gout who were intensively treated to the sUA target, work productivity and activity impairment were largely unchanged and at 1 year predicted by comorbidities and patient concerns about medication.

Exposure to specific tumour necrosis factor inhibitors and risk of demyelinating and inflammatory neuropathy in cohorts of patients with inflammatory arthritis: a collaborative observational study across five Nordic rheumatology registers.

OBJECTIVE: To compare incidences of neuroinflammatory events, including demyelinating disease (DML), inflammatory polyneuropathies (IPN) and multiple sclerosis (MS), in patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA; including psoriatic arthritis) starting a tumour necrosis factor inhibitor (TNFi), investigating whether monoclonal TNFi antibodies (other TNFis (oTNFis)) confer higher risk than etanercept. METHODS: This is an observational cohort study including patients from the five Nordic countries starting a TNFi in 2001-2020. Time to first neuroinflammatory event was identified through register linkages. We calculated crude incidence rates (cIR) per 1000 person-years and used multivariable-adjusted Cox regression to compare incidences of neuroinflammatory events overall and for DML, IPN and MS with oTNFi versus etanercept. We further examined individual TNFis and indications. RESULTS: 33 883 patients with RA and 28 772 patients with SpA were included, initiating 52 704 and 46 572 treatment courses, respectively. In RA, we observed 135 neuroinflammatory events (65% DML) with cIR of 0.38 with oTNFi and 0.34 with etanercept. The HR of oTNFi versus etanercept was 1.07 (95% CI 0.74 to 1.54) for any neuroinflammatory event, 0.79 (95% CI 0.51 to 1.22) for DML, 2.20 (95% CI 1.05 to 4.63) for IPN and 0.73 (95% CI 0.34 to 1.56) for MS. In SpA, we observed 179 events (78% DML) with cIR of 0.68 with oTNFi and 0.65 with etanercept. The HR for any neuroinflammatory event, DML, IPN and MS was 1.06 (95% CI 0.75 to 1.50), 1.01 (95% CI 0.68 to 1.50), 1.28 (95% CI 0.61 to 2.69) and 0.94 (95% CI0.53 to 1.69), respectively. CONCLUSION: The cIRs of neuroinflammatory events are higher in SpA than in RA, but the choice of specific TNFi does not seem to play an important role in the risk of neuroinflammatory events.

Haematological malignancies in patients with psoriatic arthritis overall and treated with TNF inhibitors: a Nordic cohort study.

OBJECTIVES: To evaluate the risk of haematological malignancies in patients with psoriatic arthritis (PsA) overall, and in relation to treatment with tumour necrosis factor inhibitors (TNFi). METHODS: We identified that patients with PsA starting a first TNFi from the clinical rheumatology registers (CRR) in the five Nordic countries (n=10 621) and biologics-naïve PsA patients from (1) the CRR (n=18 705) and (2) the national patient registers (NPR, n=27 286, Sweden and Denmark) from 2006 through 2019. For Sweden and Denmark, general population comparators were matched 5:1 to PsA patients on birth year, year at start of follow-up and sex. By linkage to the national cancer registers in all countries, we collected information on haematological malignancies overall, and categorised into lymphoid or myeloid types. We estimated incidence rate ratios (IRRs) with 95% CIs using modified Poisson regression for TNFi-treated versus biologics-naïve PsA patients and versus the general population adjusted for age, sex, calendar period and country. RESULTS: During 59 827 person-years, 40 haematological malignancies occurred among TNFi-treated patients with PsA resulting in a pooled IRR of 0.96 (0.68-1.35) versus biologics-naïve PsA from CRR and an IRR of 0.84 (0.64-1.10) versus biologics-naïve PsA from NPR. The IRR of haematological malignancies in PsA overall versus general population comparators was 1.35 (1.17-1.55). The estimates were largely similar for lymphoid and myeloid malignancies. CONCLUSIONS: Treatment with TNFi in patients with PsA was not associated with an increased incidence of haematological malignancies. Conversely, a moderately increased underlying risk was seen in patients with PsA compared with the general population.

Immunogenicity and safety of a three-dose SARS-CoV-2 vaccination strategy in patients with immune-mediated inflammatory diseases on immunosuppressive therapy.

OBJECTIVES: Humoral vaccine responses to SARS-CoV-2 vaccines are impaired and short lasting in patients with immune-mediated inflammatory diseases (IMID) following two vaccine doses. To protect these vulnerable patients against severe COVID-19 disease, a three-dose primary vaccination strategy has been implemented in many countries. The aim of this study was to evaluate humoral response and safety of primary vaccination with three doses in patients with IMID. METHODS: Patients with IMID on immunosuppressive therapy and healthy controls receiving three-dose and two-dose primary SARS-CoV-2 vaccination, respectively, were included in this prospective observational cohort study. Anti-Spike antibodies were assessed 2-4 weeks, and 12 weeks following each dose. The main outcome was anti-Spike antibody levels 2-4 weeks following three doses in patients with IMID and two doses in controls. Additional outcomes were the antibody decline rate and adverse events. RESULTS: 1100 patients and 303 controls were included. Following three-dose vaccination, patients achieved median (IQR) antibody levels of 5720 BAU/mL (2138-8732) compared with 4495 (1591-6639) in controls receiving two doses, p=0.27. Anti-Spike antibody levels increased with median 1932 BAU/mL (IQR 150-4978) after the third dose. The interval between the vaccine doses and vaccination with mRNA-1273 or a combination of vaccines were associated with antibody levels following the third dose. Antibody levels had a slower decline-rate following the third than the second vaccine dose, p<0.001. Adverse events were reported by 464 (47%) patients and by 196 (78%) controls. Disease flares were reported by 70 (7%) patients. CONCLUSIONS: This study shows that additional vaccine doses to patients with IMID contribute to strong and sustained immune-responses comparable to healthy persons vaccinated twice, and supports repeated vaccination of patients with IMID. TRIAL REGISTRATION NUMBER: NCT04798625.

The persistence of anti-Spike antibodies following two SARS-CoV-2 vaccine doses in patients on immunosuppressive therapy compared to healthy controls-a prospective cohort study.

BACKGROUND: The durability of vaccine-induced humoral immunity against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressive therapy is not known. The aim of this study was to compare the persistence of anti-Spike antibodies following two-dose SARS-CoV-2 vaccination between IMID patients and healthy controls and to identify factors associated with antibody decline. METHODS: IMID patients on immunosuppressive medication enrolled in the prospective observational Nor-vaC study were included. Participants received two-dose SARS-CoV-2 vaccination. Serum collected at two time points following vaccination (first assessment within 6-48 days, second within 49-123 days) were analyzed for antibodies binding the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. Multivariable regression models estimated percent reduction in anti-RBD over 30 days and factors associated with reduction. RESULTS: A total of 1108 patients (403 rheumatoid arthritis, 195 psoriatic arthritis, 195 spondyloarthritis, 124 ulcerative colitis, 191 Crohn's disease) and 134 controls provided blood samples within the defined intervals (median 19 days [IQR 15-24] and 97 days [87-105] after second vaccine dose). Antibody levels were lower in patients compared to controls at both time points, with median anti-RBD 2806 BAU/ml [IQR 1018-6068] in patients and 6187 BAU/ml [4105-7496] in controls (p<0.001) at first assessment, and 608 BAU/ml [IQR 58-1053] in patients and 1520 BAU/ml [979-3766] in controls (p<0.001) at second assessment. At second assessment, low anti-RBD antibody levels (defined as <200 BAU/ml) were found in 449 (41%) patients, and 6 (5%) controls (p<0.001). The change was - 83% in patients and - 66% in controls (p<0.001). Patients had a greater estimated 30 days percent reduction in anti-RBD levels compared to controls - 4.9 (95% CI - 7.4 to - 2.4), (p<0.05). Among therapies, mono- or combination treatment with tumor necrosis factor inhibitors was associated with the greatest decline. CONCLUSIONS: Within 4 months after vaccination, antibody levels declined considerably in both IMID patients and controls. Patients had lower initial antibody levels and a more pronounced decline compared to healthy controls and were therefore more likely to decline to low antibody levels. These results support that IMID patients need additional vaccine doses at an earlier stage than healthy individuals.

Do patient-reported measures of disease activity in rheumatoid arthritis vary between countries? Results from a Nordic collaboration.

OBJECTIVES: To investigate whether patient-reported outcomes vary across countries and are influenced by cultural/contextual factors. Specifically, we aimed to assess inter-country differences in tender joint count (TJC), pain and patient's global health assessment (PGA), and their impact on disease activity (DAS28-CRP) in RA patients from five Nordic countries. METHODS: We collected data (baseline, 3- and 12-months) from rheumatology registers in the five countries comprising RA patients starting a first ever MTX or a first ever TNF inhibitor (TNFi). In order to assess the role of context (=country), we separately modelled TJC, pain and PGA as functions of objective variables (CRP, swollen joint count, age, sex, calendar period and disease duration) with linear models. Analyses were performed at each time point and for both treatments. We further assessed the impact of inter-country differences on DAS28-CRP. RESULTS: A total of 27 645 RA patients started MTX and 19 733 started a TNFi. Crude inter-country differences at MTX start amounted to up to 4 points (28 points scale) for TJC, 10 and 27 points (0-100 scale) for pain and PGA, respectively. Corresponding numbers at TNFi start were 3 (TJC), 27 (pain) and 24 (PGA) points. All differences were reduced at 3- and 12-months, and attenuated when adjusting for the objective variables. The variation in predicted DAS28-CRP across countries amounted to <0.5 units. CONCLUSIONS: Inter-country differences in TJC, pain and PGA are greater than expected based on differences in objective measures, but have a small clinical impact on DAS28-CRP across countries.

One-Year Treatment Outcomes of Secukinumab Versus Tumor Necrosis Factor Inhibitors in Spondyloarthritis: Results From Five Nordic Biologic Registries Including More Than 10,000 Treatment Courses.

OBJECTIVE: To describe baseline characteristics and to compare treatment effectiveness of secukinumab versus tumor necrosis factor inhibitors (TNFi) in patients with spondyloarthritis (SpA) using adalimumab as the main comparator. METHODS: This was an observational, prospective cohort study. Patients with SpA (clinical ankylosing spondylitis, nonradiographic axial SpA, or undifferentiated SpA) starting secukinumab or a TNFi during 2015-2018 were identified from 5 Nordic clinical rheumatology registries. Data on comorbidities and extraarticular manifestations (psoriasis, uveitis, and inflammatory bowel disease) were captured from national registries (data available in 94% of patients) and included in multivariable analyses. We assessed 1-year treatment retention (crude survival curves, adjusted hazard ratios [HRadj ] for treatment discontinuation) and 6-month response rates (Ankylosing Spondylitis Disease Activity Score [ASDAS] score <2.1, Bath Ankylosing Spondylitis Disease Activity Index [BASDAI] <40 mm, crude/LUNDEX-adjusted, adjusted logistic regression analyses with odds ratios [ORs]) stratified by line of biologic treatment (first, second, and third plus). RESULTS: In total, 10,853 treatment courses (842 secukinumab and 10,011 TNFi, of which 1,977 were adalimumab) were included. The proportions of patients treated with secukinumab during the first, second, and third-plus lines of treatment were 1%, 6%, and 22%, respectively). Extraarticular manifestations varied across treatments, while other baseline characteristics were largely similar. Secukinumab had a 1-year retention comparable to adalimumab as a first or second line of treatment but poorer as a third-plus line of therapy (secukinumab 56% [95% confidence interval (95% CI) 51-61%] versus adalimumab 70% [95% CI 64-75%]; HRadj 1.43 [95% CI 1.12-1.81]). Across treatment lines, secukinumab had poorer estimates for 6-month response rates than adalimumab, statistically significantly only for the third-plus line (adjusted analyses: ASDAS score <2.1 OR 0.56 [95% CI 0.35-0.90]; BASDAI <40 mm OR 0.62 [95% CI 0.41-0.95]). Treatment outcomes varied across the 5 TNFi. CONCLUSION: Secukinumab was mainly used in biologics-experienced patients with SpA. Secukinumab and adalimumab performed similarly in patients who had failed a first biologic, although with increasing prior biologic exposure, adalimumab was superior.

Effects of a mindfulness-based and acceptance-based group programme followed by physical activity for patients with fibromyalgia: a randomised controlled trial.

INTRODUCTION: Non-pharmacological approaches are recommended as first-line treatment for patients with fibromyalgia. This randomised controlled trial investigated the effects of a multicomponent rehabilitation programme for patients with recently diagnosed fibromyalgia in primary and secondary healthcare. METHODS: Patients with widespread pain ≥3 months were referred to rheumatologists for diagnostic clarification and assessment of study eligibility. Inclusion criteria were age 20-50 years, engaged in work or studies at present or during the past 2 years, and fibromyalgia diagnosed according to the American College of Rheumatology 2010 criteria. All eligible patients participated in a short patient education programme before inclusion and randomisation. The multicomponent programme, a 10-session mindfulness-based and acceptance-based group programme followed by 12 weeks of physical activity counselling was evaluated in comparison with treatment as usual, that is, no treatment or any other treatment of their choice. The primary outcome was the Patient Global Impression of Change (PGIC). Secondary outcomes were self-reported pain, fatigue, sleep quality, psychological distress, physical activity, health-related quality of life and work ability at 12-month follow-up. RESULTS: In total, 170 patients were randomised, 1:1, intervention:control. Overall, the multicomponent rehabilitation programme was not more effective than treatment as usual; 13% in the intervention group and 8% in the control group reported clinically relevant improvement in PGIC (p=0.28). No statistically significant between-group differences were found in any disease-related secondary outcomes. There were significant between-group differences in patient's tendency to be mindful (p=0.016) and perceived benefits of exercise (p=0.033) in favour of the intervention group. CONCLUSIONS: A multicomponent rehabilitation programme combining patient education with a mindfulness-based and acceptance-based group programme followed by physical activity counselling was not more effective than patient education and treatment as usual for patients with recently diagnosed fibromyalgia at 12-month follow-up. TRIAL REGISTRATION NUMBER: BMC Registry (ISRCTN96836577).

Use of video consultations in an outpatient rheumatology clinic. / Bruk av videokonsultasjon ved en revmatologisk poliklinikk.

BACKGROUND: Due to the COVID-19 pandemic, the implementation of video consultations as an alternative to hospital face-to-face consultations was advanced for persons with rheumatic diseases at Diakonhjemmet Hospital. Video consultations were introduced in March 2020, and this article presents the experiences gained by healthcare professionals and patients. MATERIAL AND METHOD: The data was collected in June 2020 through focus-group interviews with healthcare professionals and through an anonymous online survey of patients who had attended video consultations during a period of three weeks in June 2020. RESULTS: The data from the focus-group interviews with seven rheumatologists and seven nurses were sorted into main thematic categories: patient, healthcare professional, consultation, and technology. The healthcare professionals felt that video consultations, with some exceptions, were appropriate in the follow-up of patients with rheumatic diseases, and especially for stable patients with no confounding issues. Of the 383 patients who were invited to participate, 139 (36 %) responded to the survey. The patients were largely satisfied with the video consultation, with a median score of 10 (quartiles 8-10) on a numerical rating scale from 0 to 10, however, 32 (27 %) patients considered the lack of clinical examination to be detrimental. INTERPRETATION: Video consultations are often appropriate in the follow-up of patients with a rheumatic disease.

Trajectories of change in symptom severity in patients with fibromyalgia: exploratory analyses of a randomised controlled trial.

The clinical picture of fibromyalgia (FM) symptoms fluctuates, and the symptom severity varies within and between patients. The current study aimed to identify groups of PDS trajectories and to explore differences in baseline characteristics between the potential groups of trajectories. We included patients from a completed randomised controlled trial, in total 170 patients diagnosed with FM according to the ACR 2010 criteria. The mean age was 40 years, and 94% were women. Symptom severity was assessed by the Polysymptomatic distress scale (PDS) [range 0 (no symptoms) to 31] at four timepoints over 13-18 months. Latent class growth analysis was used to identify patient trajectories based on their response pattern on the PDS. Potential differences in baseline characteristics between the trajectories were compared using appropriate statistical tests. Two distinct PDS trajectories were identified with 110 patients (65%) classified as the "no improvement" group and 60 (35%) as the "some improvement" group. Mean PDS scores at pre-baseline were ≥ 20 in both groups. At 12 months, the groups diverged, mean (SD) PDS score was 14 (3.82) in the "some improvement" group and 21 (4.12) in the "no improvement" group. There were no significant differences in baseline characteristics between the groups of PDS trajectories. We identified one group of FM patients that improved slightly during the study period and one group that not improved. There were no differences in baseline characteristics between the two groups.

Trajectories of fatigue in actively treated patients with established rheumatoid arthritis starting biologic DMARD therapy.

OBJECTIVES: To define fatigue trajectories in patients with rheumatoid arthritis (RA) who initiate biological DMARD (bDMARD) treatment, and explore baseline predictors for a trajectory of continued fatigue. METHODS: One-hundred and eighty-four patients with RA initiating bDMARDs were assessed at 0, 1, 2, 3, 6 and 12 months. Swollen and tender joint counts, patient reported outcomes (PROMs), blood samples and ultrasound examinations were collected at each time point. Fatigue was assessed by the fatigue Numeric Rating Scale (0-10) from the Rheumatoid Arthritis Impact of Disease (RAID) questionnaire. Clinically significant fatigue was predefined as fatigue ≥4. Three trajectories of interest were defined according to level of RAID fatigue: no fatigue (≤3 at 5/6 visits), improved fatigue (≥4 at start, but ≤3 at follow-up) and continued fatigue (≥4 at 5/6 visits). Baseline variables were compared between groups by bivariate analyses, and logistic regression models were used to explore baseline predictors of continued vs improved fatigue. RESULTS: The majority of patients starting bDMARD therapy followed one of three fatigue trajectories, (no fatigue; n=61, improved; n=33 and continued fatigue; n=53). Patients with continued fatigue were more likely to be anti-citrullinated protein antibody and/or rheumatoid factor positive and had higher baseline PROMs compared to the other groups, while there were no differences between the groups for variables of inflammation including. Patient global, tender joint count and anxiety were predictors for the continued fatigue trajectory. DISCUSSION: A trajectory of continued fatigue was determined by PROMs and not by inflammatory RA disease activity.

Fibromyalgia in patients with rheumatoid arthritis. A 10-year follow-up study, results from the Oslo Rheumatoid Arthritis Register.

OBJECTIVES: To examine cross-sectional and longitudinal relationships between fibromyalgia (FM) and rheumatoid arthritis (RA) disease activity. METHODS: 636 patients in the observational Oslo RA register (ORAR) were invited to a clinical examination in 1999. 28-tender and swollen joint counts (TJC, SJC) and 18-tender points were assessed, the RA disease activity score (DAS-28) calculated. Fibromyalgia (FM) was diagnosed according to 1990 (FM-1990) and modified 2011 (mFM-2011) ACR criteria. At the 10-year follow-up patients completed the RA Disease Activity Index (RADAI) and Routine Assessment of Patient Index Data 3 (RAPID-3). Baseline and 10-year RA disease activity were compared across presence/absence of FM. Linear regression models were constructed with 10-year RADAI and RAPID-3 as outcome. RESULTS: 502 patients participated at baseline data-collection and 10-year data was available in 236. At baseline, mean (SD) age was 59.5 (12.5) years and 87% were female. 9% and 30% had FM-1990 and mFM-2011 respectively. RA-FM patients were predominantly female with higher SJC, TJC, and DAS-28 at baseline. Baseline RA-FM predicted higher levels of RADAI and RAPID-3 at the 10-year follow-up. CONCLUSIONS: RA-FM was associated with significantly higher levels of cross-sectional and longitudinal RA disease activity. FM should be considered in patients with RA not reaching remission.

Effects of a community-based multicomponent rehabilitation programme for patients with fibromyalgia: protocol for a randomised controlled trial.

INTRODUCTION: People with fibromyalgia (FM) suffer from symptoms such as widespread pain, non-refreshing sleep, fatigue and reduced quality of life. Effects of pharmacological treatment are questionable and non-pharmacological treatments are recommended as first-line therapy. To date the majority of patients with FM in Norway are not offered any targeted treatment. The aim of this randomised controlled trial is to investigate the effects of a community-based multicomponent rehabilitation programme comprising an acceptance-based and mindfulness-based group intervention, the Vitality Training Programme (VTP), followed by tailored physical activity counselling. MATERIALS AND METHODS: General practitioners refer potential participants to a rheumatologist in specialist healthcare for diagnostic clarification and assessment of comorbidities. Inclusion criteria are widespread pain/FM ≥3 months, age 20-50 and work participation (minimum part-time) within the last 2 years. The intervention group attends the VTP comprising 10 weekly 4 hour group sessions plus a booster session after 6 months. Thereafter, they receive 12 weeks of individually tailored physical exercise counselled by physiotherapists at community-based Healthy Life Centers. The control group follows treatment as usual. The primary outcome is Patient Global Impression of Change. Secondary outcomes include self-reported pain, fatigue and sleep quality, psychological distress, mindfulness, health-related quality of life, physical activity, work ability and exercise beliefs and habits. To achieve a power of 80% and allow for 10% dropout, 70 participants are needed in each arm. All analyses will be conducted on intention-to-treat bases and measured as differences between groups at 12 months follow-up. ETHICS AND DISSEMINATION: The study is approved and granted by the Norwegian South-Eastern Regional Health Authority (reference 2016015). Ethics approval was obtained from Regional Committee for Medical and Health Research Ethics (reference 2015/2447/REK sør-øst A). Results will be submitted to appropriate journals and presented in relevant conferences and social media. TRIAL REGISTRATION: ISRCTN 96836577.

The Impact of Newer Biological Disease Modifying Anti-Rheumatic Drugs on Cardiovascular Risk Factors: A 12-Month Longitudinal Study in Rheumatoid Arthritis Patients Treated with Rituximab, Abatacept and Tociliziumab.

OBJECTIVES: To assess whether treatment with one of three novel biological DMARDs; rituximab, abatacept or tocilizumab reduce cardiovascular disease (CVD) risk factors in patients with rheumatoid arthritis (RA). METHODS: This is an open, observational and prospective study with visits at baseline, 3, 6, and 12 months. Patients were assigned to receive rituximab, abatacept or tocilizumab according to clinical indications assessed by an independent rheumatologist. Disease activity was quantified by the disease activity score (DAS28) and extensive ultrasonography. CVD risk was assessed by total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), blood pressure and arterial stiffness measurements [pulse wave velocity (PWV) and augmentation index (AIx)]. Within group change in disease activity and CVD risk over 3 months was explored using paired samples bivariate tests. Predictors of change in CVD risk at 3 months were identified in linear regression models. Changes in CVD risk markers over the 12- month follow-up in patients receiving rituximab were assessed by mixed models repeated analyses. RESULTS: 24 patients on rituximab, 5 on abatacept and 7 on tocilizumab were included. At 3 months PWV was significantly reduced in the tocilizumab group only, but at 12 months rituximab patients showed a significant reduction in PWV. Reduced inflammation at 3 months was associated with increased TC and HDL-c in the entire cohort. CONCLUSION: Treatment with tocilizumab and rituximab reduces PWV, a marker of CVD risk, in patients with RA.

Efficacy of high intensity exercise on disease activity and cardiovascular risk in active axial spondyloarthritis: a randomized controlled pilot study.

BACKGROUND: Physical therapy is recommended for the management of axial spondyloarthritis (axSpA) and flexibility exercises have traditionally been the main focus. Cardiovascular (CV) diseases are considered as a major health concern in axSpA and there is strong evidence that endurance and strength exercise protects against CV diseases. Therefore, the aim of this study was to investigate the efficacy of high intensity endurance and strength exercise on disease activity and CV health in patients with active axSpA. METHODS: In a single blinded randomized controlled pilot study the exercise group (EG) performed 12 weeks of endurance and strength exercise while the control group (CG) received treatment as usual. The primary outcome was the Ankylosing Spondylitis (AS) Disease Activity Score (ASDAS). Secondary outcomes included patient reported disease activity (Bath AS Disease Activity Index [BASDAI]), physical function (Bath AS Functional Index [BASFI]), and CV risk factors measured by arterial stiffness (Augmentation Index [Alx]) and Pulse Wave Velocity [PWV]), cardiorespiratory fitness (VO2 peak) and body composition. ANCOVA on the post intervention values with baseline values as covariates was used to assess group differences, and Mann Whitney U-test was used for outcomes with skewed residuals. RESULTS: Twenty-eight patients were included and 24 (EG, n = 10, CG, n = 14) completed the study. A mean treatment effect of -0.7 (95%CI: -1.4, 0.1) was seen in ASDAS score. Treatment effects were also observed in secondary outcomes (mean group difference [95%CI]): BASDAI: -2.0 (-3.6, -0.4), BASFI: -1.4 (-2.6, -0.3), arterial stiffness (estimated median group differences [95% CI]): AIx (%): -5.3 (-11.0, -0.5), and for PVW (m/s): -0.3 (-0.7, 0.0), VO2 peak (ml/kg/min) (mean group difference [95%CI]: 3.7 (2.1, 5.2) and trunk fat (%): -1.8 (-3.0, -0.6). No adverse events occurred. CONCLUSION: High intensity exercise improved disease activity and reduced CV risk factors in patients with active axSpA. These effects will be further explored in a larger trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT01436942.