Sex differences in cytokines and adipokines in obese patients with PsA and controls undergoing a weight loss intervention.

OBJECTIVE: In this post hoc analysis of a previously published study, we compared cytokines and adipokine levels in women and men with psoriatic arthritis (PsA) at baseline (BL) and 6 months (M6) following a weight loss intervention. METHODS: Patients with PsA (n=41) between 25 and 75 years of age, with body mass index (BMI)≥33 kg/m2 were included in a weight loss intervention with a very low energy diet (VLED) for 12 or 16 weeks depending on BL BMI<40 or ≥40 kg/m2. As controls (n=39), obese individuals, already planned for VLED treatment were recruited and matched for sex, age and weight to the patients with PsA. Cytokines and adipokines were measured at BL and M6. RESULTS: At BL, serum levels of interleukin (IL)-23, leptin and high molecular weight-adiponectin were higher in women with PsA compared with men, whereas serum levels of interferon (IFN)-γ, IL-12/IL-23 p40 and IL-13 were significantly lower in women. Serum IL-23 was significantly reduced at M6 compared with BL in women but not in men with PsA. In women with PsA, the reduction in IL-23 at M6, ∆IL-23, were positively correlated with ∆Disease Activity Score 28 C reactive protein (CRP) (Spearman's correlation (rS)=0.486, p=0.016), ∆CRP (rS=0.468, p=0.021), ∆leptin (rS=0.683, p<0.001) and negatively correlated with ∆total-adiponectin (rS=-0.433, p=0.035). Also in women, ∆Disease Activity in Psoriatic Arthritis was positively correlated with ∆tumour necrosis factor-α (rS=0.417, p=0.034), ∆IL-1ß (rS=0.550, p=0.034), ∆IFN-γ (rS=0.414, p=0.035) and ∆leptin (rS=0.410, p=0.038). None of these correlations were significant in men with PsA. CONCLUSIONS: Women and men with PsA differed with regard to serum levels of cytokines and adipokines before and after weight loss.

The impact of a structured weight-loss treatment on physical fitness in patients with psoriatic arthritis and obesity compared to matched controls: a prospective interventional study.

OBJECTIVES: To evaluate the effects of weight loss treatment on physical fitness in patients with psoriatic arthritis (PsA) and obesity compared to matched controls. METHODS: In total, 46 patients with PsA (CASPAR) and BMI ≥ 33 kg/m2 and 52 obese persons were included in this 12-month prospective open intervention study with a very low energy diet (640 kcal/day), followed by structured reintroduction of an energy-restricted diet and brief support for physical activity. The primary outcome was muscle strength assessed with hand-grip strength (Grippit) and leg muscle strength (timed stand test). Secondary outcomes were cardiorespiratory fitness, body composition, and physical functioning (SF-36PCS). Outcomes were assessed at baseline, 6 (M6), and 12 months (M12). Nonparametric statistics were used. RESULTS: Median weight reduction at M6 was 18.9 kg in patients and 23.0 kg in controls, (p = 0.546). At M12, patients' median weight loss from baseline was 16.1 kg, corresponding with significant loss of total fat mass (- 30.1%), and lean mass (total - 7.0%, arm - 13.7%, and leg - 6.0%). Leg muscle strength improved in patients and controls at M6 (p < 0.001) and remained improved at M12 (p < 0.01), while hand-grip strength was unchanged in both groups. Cardiorespiratory fitness increased in controls at M6 (p = 0.018) and M12 (p = 0.028) but not in patients. Physical functioning improved in both groups at M6 (p < 0.001) and remained improved at M12 (p = 0.008) and (p < 0.01), respectively. CONCLUSION: The intervention resulted in positive effects on body weight and total body fat. Despite reduced lean body mass, the muscle strength did not deteriorate in patients with PsA and controls. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02917434, registered on September 21, 2016-retrospectively registered.

Supervised Intensive Exercise for Strengthening Exercise Health Beliefs in Patients With Axial Spondyloarthritis: A Multicenter Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of a 3-month supervised high-intensity exercise program on exercise health beliefs in patients with axial spondyloarthritis. METHODS: This was secondary analysis of a randomized controlled trial. Participants (ages 23-69 years) were randomized to an exercise group (n = 50) or a control group (n = 50). The intervention was an individually guided cardiorespiratory and strength exercise program performed 2 times per week, plus an additional individual exercise session of personal choice. The control group received standard care and instructions to maintain their physical activity level. Exercise health beliefs using the Exercise Health Beliefs questionnaire (range 20-100, 100 = best), i.e., barriers, benefits, self-efficacy and exercise impact on arthritis, and physical activity, were assessed with self-reported questionnaires at baseline, 3 months, and 12 months after inclusion. RESULTS: The majority of the participants in the exercise group (76%) followed ≥80% of the prescribed exercise protocol. There was a significant effect of the intervention on exercise health beliefs at 3 months (estimated mean group differences 4.0 [95% confidence interval (95% CI) 1.4, 6.6]; P = 0.003) and the effect persisted at 12 months follow-up (estimated mean group differences 3.8 [95% CI 1.0, 6.6]; P = 0.008). Participants with higher exercise health beliefs had a higher odds ratio (1.1 [95% CI 1.0, 1.20]; P = 0.003) for being physically active at 12 months follow-up. CONCLUSION: A supervised high-intensity exercise program had beneficial short- and long-term effects on participants' exercise health beliefs. Stronger exercise health beliefs were positively associated with a higher chance to be physically active on a health-enhancing level at 12 months follow-up.

Weight loss is associated with sustained improvement of disease activity and cardiovascular risk factors in patients with psoriatic arthritis and obesity: a prospective intervention study with two years of follow-up.

BACKGROUND: Obesity is overrepresented in patients with psoriatic arthritis (PsA) and associated with increased disease activity. We have previously shown in 41 patients with PsA (Caspar criteria) and obesity (body mass index; BMI ≥33 kg/m2) that weight loss treatment with Very Low Energy Liquid Diet (VLED), 640 kcal/day during 12-16 weeks, followed by a structured reintroduction of an energy restricted diet resulted in a median weight loss of 18.6% and concomitantly a significant improvement of the disease activity in joints, entheses and skin. The objectives of this follow-up were to study the effects of the weight loss treatment on disease activity in longer term (12 and 24 months) and to study the effects on cardiovascular risk factors. METHODS: The patients were assessed with 66/68 joints count, Leeds enthesitis index (LEI), body surface area, blood pressure, BMI, questionnaires and fasting blood samples at the 12- and 24-month visits. RESULTS: In total, 39 and 35 PsA patients attended the 12- and the 24-month visits, respectively. Median weight loss since baseline was 16.0% (IQR 10.5-22.4) and 7.4% (IQR 5.1-14.0) at the 12- and 24-months follow-up. The 66/68 swollen/tender joints score, LEI, CRP and HAQ score were still significantly reduced at the 12- and 24-month visits compared to baseline. The number of patients with Minimal Disease Activity increased from 28.2% (11/39) at baseline, to 38.5% (15/39; p = 0.008) and 45.7% (16/35; p = 0.016) at the 12- and 24-month visits. The weight loss was also associated with improved levels of serum lipids, glucose and urate and the antihypertensive treatment was reduced or stopped in five patients during the follow-up. CONCLUSIONS: Weight loss treatment, with VLED included in the program, was associated with long-term improvement of measures of disease activity, self-reported function and markers of the metabolic syndrome after 24-months follow-up. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02917434 , Registered September 28, 2016- Retrospectively registered.

High-Intensity Exercise Improves Fatigue, Sleep, and Mood in Patients With Axial Spondyloarthritis: Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: Although exercise is recommended in the treatment of axial spondyloarthritis (axSpa), the focus has been on flexibility, and the effect of high-intensity exercises is unknown. The purpose of this study was to investigate the effect of high-intensity exercises on fatigue, sleep, and mood in patients with axSpA. METHODS: In this secondary analysis of a randomized controlled trial, participants were recruited from outpatient clinics at 4 hospitals in Scandinavia. A total of 100 patients with axSpA were randomized to either an exercise group (n = 50) or a control group (n = 50). High-intensity exercise was provided 3 times per week for 3 months and supervised by a physical therapist. The controls received no intervention. Measurements were self-reported at baseline, 3 months, and 12 months: fatigue, using the Fatigue Severity Scale (range = 0-7, 7 = worst, ≥5 = severe); vitality, using the RAND 36-item short-form health survey (SF-36, range = 0-100, 100 = best); sleep, using the Pittsburgh Sleep Quality Index (range = 0-21, 21 = worst, >5 = poor quality); mood, using the General Health Questionnaire 12 (range = 0-36, 36 = worst); and general health, using the EUROQoL (range = 0-100, 100 = best). RESULTS: A total of 38 participants (76%) in the exercise group followed ≥80% of the exercise protocol. At 3 months, there was a significant beneficial effect on fatigue (mean group differences = -0.4, 95% CI = -0.7 to -0.1), vitality (5.0, 95% CI = 1.1 to 10.5), mood (-2, 95% CI = -3.7 to -0.04), and general health (9.0, 95% CI = 3.3 to 14.7) but no effect on sleep (-1.1, 95% CI = -2.1 to 0.2). Compared with the control group, the exercise group had a reduced rate of severe fatigue and poor sleep. No differences were seen between the groups at 12 months. CONCLUSIONS: A 3-month exercise program had a beneficial effect on fatigue, sleep, mood, and general health in patients with axSpA at the end of the intervention; however, no long-term effects were seen. IMPACT: High-intensity cardiorespiratory and strength exercises should be considered as important in exercise programs for patients with axSpA.

How Do Patients With Axial Spondyloarthritis Experience High-Intensity Exercise?

OBJECTIVE: In a few studies, high-intensity exercise has displayed beneficial effects on cardiovascular health among patients with rheumatic diseases, yet the high-intensity exercise mode is still not fully accepted among health care professionals. The aim of this study was to investigate experiences of high-intensity exercise among patients with axial spondyloarthritis. METHODS: Fourteen respondents who had participated in a high-intensity exercise program for 12 weeks were included in this qualitative study with individual semistructured, in-depth interviews. The respondents' median age was 53, ranging from 23 to 63 years old, and both men and women of different ethnicities were represented. Interviews were analyzed by qualitative content analysis, including both manifest content and interpretations of underlying latent meaning. RESULTS: The analysis resulted in five categories describing the respondents' experiences with high-intensity exercise: 1) high-intensity exercise as a challenge for both body and mind, 2) increased faith in one's own body, 3) changed attitude toward exercise, 4) taking charge of one's own health by challenging the disease, and 5) exercise in a social context. CONCLUSION: Supervised high-intensity interval exercise was perceived as challenging for both body and mind but was also described as a positive experience, with rapid bodily effects that strengthened respondents' faith in their own bodies. The new experience seemed to have changed the respondents' attitude and motivation for exercise and made them start taking charge of their health by challenging the disease. Exercise in a social context, under professional leadership, enhanced exercise self-efficacy and helped the respondents to adhere to the exercise program.

Responsiveness and Interpretability of 2 Measures of Physical Function in Patients With Spondyloarthritis.

BACKGROUND: Maintenance or improvement of physical function is an important treatment target in the management of patients with axial spondyloarthritis (axSpA); measurement tools that can detect changes in physical function are therefore important. OBJECTIVES: The objective of this study was to compare responsiveness and interpretability of the patient-reported Bath Ankylosing Spondylitis Functional Index (BASFI) and the Ankylosing Spondylitis Performed-Based Improvement (ASPI) in measuring change in physical function after exercise in patients with axSpA. DESIGN: This was a sub-study of 58 patients nested within a randomized controlled trial comparing the effect of 12 weeks of exercise with usual care. METHODS: Responsiveness and interpretability were assessed according to the Consensus-based Standards for the selection of health status Measurement Instrument. Responsiveness was assessed by testing 8 predefined hypotheses for ASPI and BASFI. Interpretability was assessed by: (1) using patients' reported change as an anchor ("a little better" = minimal important change) and (2) by categorizing patients with a 20% improvement as responders. RESULTS: For ASPI and BASFI, 5 of 8 (63%) versus 2 of 8 (25%) of the predefined hypotheses for responsiveness were confirmed. The minimal important change values for improvement in physical function were 3.7 seconds in ASPI and 0.8 points (on a scale from 0 to 10) for BASFI. In the intervention group, 21 of 30 (70%) and 13 of 30 (43%) of the patients were categorized as responders measured with ASPI and BASFI, respectively. There was a tendency towards a floor effect in BASFI, as 8 of 58 (14%) patients scored the lowest value at baseline. LIMITATIONS: This study was limited by its moderate sample size. CONCLUSIONS: Our findings suggest that ASPI is preferable over BASFI when evaluating physical function after exercise interventions in patients with axSpA.

High intensity exercise for 3 months reduces disease activity in axial spondyloarthritis (axSpA): a multicentre randomised trial of 100 patients.

BACKGROUND: Exercise is considered important in the management of patients with rheumatic diseases, but the effect of high intensity exercises on disease activity is unknown. OBJECTIVE: To investigate the effectiveness of high intensity exercises on disease activity in patients with axial spondyloarthritis (axSpA). METHOD: Assessor blinded multicentre randomised controlled trial. 100 patients (aged from their 20s to their 60s) with axSpA were randomly assigned to an exercise group or to a no-intervention control group. The exercise group performed cardiorespiratory and muscular strength exercises at high intensity over 3 months. The control group received standard care and was instructed to maintain their usual physical activity level. Primary outcome was disease activity measured with the Ankylosing Spondylitis (AS) Disease Activity Scale (ASDAS, higher score=worst) and the Bath AS Disease Activity Index (BASDAI, 0-10, 10=worst). Secondary outcomes were inflammatory markers, physical function and cardiovascular (CV)-health. There was patient involvement in the design and reporting of this study. RESULTS: 97 of the 100 (97%) randomised patients completed the measurements after the intervention. There was a significant treatment effect of the intervention on the primary outcome (ASDAS: -0.6 [-0.8 to -0.3], p<0.001 and BASDAI: -1.2 [-1.8 to -0.7], p<0.001). Significant treatment effects were also seen for inflammation, physical function and CV-health. CONCLUSION: High intensity exercises reduced disease symptoms (pain, fatigue, stiffness) and also inflammation in patients with axSpA. It improves patients' function and CV health. This debunks concerns that high intensity exercise might exacerbate disease activity in patients with axSpA. TRIAL REGISTRATION NUMBER: NCT02356874.

Longterm Effect on Leisure Time Physical Activity Level in Individuals with Axial Spondyloarthritis: Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: To explore the longterm effect of a 3-month exercise program on leisure time physical activity level in individuals with axial spondyloarthritis (axSpA). METHODS: A secondary analysis was performed on data from 100 individuals with axSpA who were included in a randomized controlled trial. The exercise group (EG) participated in a 3-month exercise program while the control group (CG) received no intervention. Physical activity during leisure time was measured with a questionnaire (physically active: ≥ 1 h/week with moderate/vigorous intensity physical activity). Disease activity was measured with the Ankylosing Spondylitis Disease Activity Scale (ASDAS; higher score = worst). Statistical analyses were performed on an intention-to-treat basis using chi-square tests, logistic regression, and mixed models. RESULTS: At the 12-month followup, significantly more individuals in the EG than in the CG were physically active [29 (67%) vs 13 (30%), p < 0.001] and exercised 2-3 times/week [25 (58%) vs 15 (34%), p = 0.02], and fewer exercised at light intensity [3 (8%) vs 14 (44%), p = 0.002]. "Participation in the EG" (OR 6.7, 95% CI 2.4-18.6, p < 0.001) and "being physically active at baseline" (OR 4.7, 95% CI 1.4-15.8, p = 0.01) were the factors most associated with being physically active. There were no differences between the groups in ASDAS (p = 0.79). CONCLUSION: A 3-month exercise program had a beneficial longterm effect on leisure time physical activity in individuals with axSpA, thus indicating a more beneficial health profile. Still, few individuals continued the intensive program, and there was no difference between the groups in disease activity after 12 months. (ClinicalTrials.gov: NCT02356874).

Weight loss improves disease activity in patients with psoriatic arthritis and obesity: an interventional study.

BACKGROUND: Obesity is over-represented in patients with psoriatic arthritis (PsA) and associated with higher disease activity, poorer effect of treatment and increased cardiovascular morbidity. Studies on the effects of weight loss are however needed. This study aimed to prospectively study the effects of weight loss treatment with very low energy diet (VLED) on disease activity in patients with PsA (CASPAR criteria) and obesity (body mass index BMI ≥ 33 kg/m2). METHODS: VLED (640 kcal/day) was taken during 12-16 weeks, depending on pre-treatment BMI. Afterwards, an energy-restricted diet was gradually reintroduced. Weight loss treatment was given within a structured framework for support and medical follow-up. Treatment with conventional synthetic and/or biologic disease-modifying anti-rheumatic drugs was held constant from 3 months before, until 6 months after baseline. Patients were assessed with BMI, 66/68 joints count, Leeds enthesitis index, psoriasis body surface area (BSA), questionnaires and CRP at baseline, 3 and 6 months. Primary outcome was the percentage of patients reaching minimal disease activity (MDA) and secondary outcomes were reaching Psoriatic Arthritis Response Criteria (PsARC) and American College of Rheumatology (ACR) response criteria. RESULTS: Totally 41/46 patients completed the study, 63% women, median age 54 years (IQR 48-62). At baseline increased BMI was associated with higher disease activity and poorer function. The median weight loss was 18.7 kg (IQR 14.6-26.5) or 18.6% (IQR 14.7-26.3) of the baseline weight. A majority of the disease activity parameters improved significantly after weight loss, including 68/66 tender/swollen joints count, CRP, BSA, Leeds enthesitis index, HAQ and patient VAS for global health, pain and fatigue. A larger weight loss resulted in more improvement in a dose-response manner. The percentage of patients with MDA increased from 29 to 54%, (p = 0.002). PsARC was reached by 46.3%. The ACR 20, 50 and 70 responses were 51.2%, 34.1% and 7.3% respectively. CONCLUSIONS: Short-term weight loss treatment with VLED was associated with significant positive effects on disease activity in joints, entheses and skin in patients with PsA and obesity. The study supports the hypothesis of obesity as a promotor of disease activity in PsA. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02917434 , registered on September 21, 2016-retrospectively registered.

Significantly impaired shoulder function in the first years of rheumatoid arthritis: a controlled study.

INTRODUCTION: Patients with rheumatoid arthritis (RA) risk impaired shoulder function due to the inflammatory process. The knowledge of shoulder function in the early years of the disease is limited. The aim was to compare shoulder function and activity limitation related to the shoulder-arm-hand in women with RA in early disease course compared to age-matched healthy women. METHOD: This controlled cross-sectional study included 103 women with rheumatoid arthritis and a reference group of 103 age-matched healthy women. The mean age was 47.1 (SD 10.0) years, the mean disease duration was 20.3 (SD 8.5) months and the mean DAS28 score was 3.8 (SD 1.4) among the patients. Participants were provided with self-reported questionnaires quantifying activity limitations. Shoulder function was assessed by isometric strength of the shoulder, shoulder-arm movement and shoulder pain. Hand-grip force was assessed and examination was made of tender and swollen joints among the patients. RESULTS: Patients showed significantly (p < 0.0001) impaired shoulder muscle strength, shoulder-arm movement, and shoulder pain compared to the reference group. Patients shoulder muscle strength was approximately 65% of the results observed in the reference group. Activity limitations related to the shoulder-arm-hand (DASH) were significantly (p < 0.0001) higher in the patient group compared to the reference group and indicates limitations in daily activities for the patients. CONCLUSION: Patients with RA were found to have significantly impaired shoulder function already 1.5 years after disease onset compared to age-matched subjects. Reduced shoulder muscle strength was found to be associated with activity limitations (DASH) implying that screening of the shoulder function, emphasising the shoulder muscle strength, should be initiated from disease onset.

Disability of the Arm, Shoulder and Hand questionnaire in Swedish patients with rheumatoid arthritis: A validity study.

OBJECTIVE: The aim of this study was to assess the reliability and validity of the Disability of the Arm, Shoulder and Hand (DASH) questionnaire in a Swedish rheumatoid arthritis population. METHODS: To investigate the concurrent and convergent validity, 67 patients with rheumatoid arthritis completed the DASH, the Health Assessment Questionnaire Disability Index (HAQ) and activity-induced pain. Active shoulder-arm motion, handgrip force and disease activity (Disease Activity Score in 28 joints; DAS28) were assessed. The test-retest reliability was investigated in 26 patients. Face validity was also investigated. RESULTS: Spearman's correlation coefficient revealed a significant association (p < 0.001) between the DASH score and HAQ index (rs 0.80), confirming satisfactory concurrent validity. A significant association (p ≤ 0.02) was found between the DASH score and active shoulder-arm motion (rs ­0.38 to ­0.50), handgrip force (rs ­0.46 to ­0.59), activity-induced pain (rs 0.66) and DAS28 (rs 0.63), confirming satisfactory convergent validity for the DASH questionnaire. Satisfactory test-retest reliability (intraclass correlation coefficient 0.99, 95% confidence interval 0.98­0.99) and face validity of the questionnaire were confirmed. CONCLUSION: The DASH questionnaire showed satisfactory test-retest reliability, concurrent-, convergent-, and face validity for patients with rheumatoid arthritis and can be recommended for use in rheumatoid arthritis populations.