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

Arthritis Research & Therapy volume 21, Article number: 17 (2019) Cite this article

Abstract

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

Background

Psoriasis affects 2–3% of the population in Sweden and 20–30% of individuals with psoriasis develop psoriatic arthritis (PsA), a chronic rheumatic disease leading to synovitis, enthesitis and sometimes also axial involvement [1]. Both psoriasis and PsA are strongly associated with obesity and the metabolic syndrome (MetS) [2]. International observational studies have reported prevalence of obesity (body mass index (BMI) ≥ 30 kg/m2) in 45% of PsA patients and of MetS in 30–45% [3,4,5]. Previous studies have shown that obesity increases the risk of developing both psoriasis and PsA and that obesity is associated with higher disease activity, poorer treatment response and lower chance of achieving minimal disease activity (MDA) [3, 6,7,8,9,10]. Patients with PsA also have an increased risk of cardiovascular disease (CVD) [11,12,13]. Chronic inflammation, which accelerates the atherosclerotic process, in combination with higher prevalence of cardiovascular (CV) risk factors among PsA patients is believed to contribute to this increased risk [14,15,16].

Although the associations between PsA and obesity, BMI and disease activity are well known, there is to the best of our knowledge only one prior interventional study which has prospectively assessed the effects of weight loss treatment in PsA [17].

The aim of this study was to determine the effects of weight loss treatment with very low energy diet (VLED) on the disease activity in joints, entheses and skin in patients with PsA and obesity. The primary endpoint of the study was the percentage of patients reaching minimal disease activity (MDA) after 6 months weight loss treatment. Secondary endpoints were the percentage of patients reaching American College of Rheumatology (ACR) and Psoriatic Arthritis Response Criteria (PsARC).

Patients and methods

Patients

Patients with PsA and obesity registered at the Rheumatology clinics of Sahlgrenska University hospital and the hospitals of Alingsås and Borås were invited to participate.

Patients with PsA fulfilling the Classification for Psoriatic Arthritis (CASPAR) criteria, with a BMI ≥ 33 kg/m2 and age 25–75 years were eligible for inclusion [18]. If using conventional synthetic and/or biologic disease-modifying anti-rheumatic drugs (cs and/or bDMARDs), the treatment had to be constant and unchanged from 3 months prior to baseline until 6 months after baseline. Exclusion criteria were pregnancy, porphyria, epilepsy, type 1 diabetes, severe heart, kidney or catabolic disease, binge eating disorders, treatment with warfarin, lithionin or phenantoin, mental imbalance affecting participation, being subject to a heart infarction, stroke, major surgery or trauma during last the 3 months and being treated for cancer during the last 5 years.

All the patients in the study gave their written informed consent. The study was approved by the Regional Ethics Committee in Gothenburg and carried out in accordance with the Helsinki Declaration.

Intervention: weight loss treatment with very low energy diet (VLED)

Weight loss treatment with VLED (< 800 kcal/day) is an effective and established method in clinical use in Sweden. In severe obesity, BMI ≥ 35.0 kg/m2, a rigorous energy restriction is needed for optimal weight loss [19]. The VLED used in the present study provided a daily intake of 640 kcal including recommended doses of vitamins, minerals and other essential nutrients (Cambridge Weight Plan Limited, Corby, UK). The diet consisted of four daily portions of powder dissolved in cold or hot water and consumed as shakes or soups. Based on pre-treatment BMI (< 40 or ≥ 40 kg/m2), the participants followed an initial period of 12 or 16 weeks on strict VLED. In addition, non-energy-containing beverages were allowed at libitum. During VLED, the mean weight loss usually is 1–2 kg per week. Adherence to treatment was controlled by measuring the body weight of the patients regularly. Absent or limited weight loss was considered a sign of poor adherence to the diet.

After the strict period, food was gradually reintroduced during a period of 12 weeks. Each patient was instructed to follow an energy-restricted diet based on individual energy requirements for weight stability reduced by 30% to achieve further weight loss. The side effects of the VLED treatment are mostly mild to moderate and transient and ceases when the strict period is ended. The most prevalent side effects are headache, nausea, obstipation, dryness of skin and hair loss [19]. The treatment is not associated with any health risks, when given under the surveillance of health professionals following an evidence-based protocol [19, 20]. The treatment was given within the framework of a 12-month protocol including structured weight loss treatment, support and medical follow-up from a team of doctors, nurses and dieticians at the Obesity Unit at Sahlgrenska University Hospital.

Measures of assessment

All examinations were done at baseline, after 3 months and 6 months. No blinding of assessors was made. Body height and weight were measured with a calibrated ruler and digital scale. Waist circumference was measured with a tape measure in centimetres midway between the lower rib and iliac crest. Joints were examined with 66/68 swollen/tender joints count and entheses with Leeds enthesitis index [21]. The extent of psoriasis was evaluated with body surface area (BSA) [22]. Quality of life related to psoriasis was assessed with the Dermatology Life Quality Index (DLQI) [23]. The patients’ disease activity was assessed with visual analogue scales (VAS) for global disease activity, pain and fatigue. The physician’s global assessment of disease activity was also evaluated with a VAS. Function and activity limitations were assessed using the Health Assessment Questionnaire (HAQ) [24]. Both the Disease Activity Score using 28 joint counts based on CRP (DAS28CRP) and the Disease Activity in PSoriatic Arthritis (DAPSA) score were calculated [25, 26].

The primary endpoint minimal disease activity (MDA) is defined as meeting five of the seven following criteria: tender joint count 68 ≤ 1, swollen joint count 66 ≤ 1, psoriasis body surface area ≤ 3%, patient pain VAS ≤ 15 mm, patient global disease activity VAS ≤ 20 mm, HAQ ≤ 0.5 and tender entheseal points ≤ 1 [27].

Secondary endpoints were the number of patients reaching the PsA Response Criteria (PsARC) and the American College of Rheumatology (ACR) 20, 50 and 70 criteria for treatment response. The PsARC is defined as improvement in at least two of the following four areas: ≥ 20% improvement in physician’s global VAS, ≥ 20% improvement in patient global disease activity VAS, ≥ 30% improvement in 66 swollen joint count, ≥ 30% improvement in 68 tender joint count. Improvement in the swollen or tender joint counts is mandatory, and there should be no worsening of any component [28, 29]. The ACR 20, 50 and 70 criteria are defined as a 20%, 50% or 70% improvement in the 28 swollen or tender joint counts together with a 20%, 50% or 70% improvement in at least 3/5 of the following: the patient’s global health VAS, patient’s pain VAS, physician’s global VAS, HAQ and CRP or ESR [30].

Blood samples were analysed for haemoglobin (Hb), white blood cell count (WBC), platelet count (PLT) and C-reactive protein (CRP) using standard laboratory techniques at Sahlgrenska University Hospital.

Statistical analyses

Statistical analyses were made using SPSS Statistics version 25 (IBM, Chicago, USA). Descriptive statistics are presented as median and interquartile range (IQR) and range. Wilcoxon signed rank test was used to compare continuous related samples and McNemar test to compare categorical related samples. Correlations were calculated using Spearman’s correlation (rS). All tests were two-tailed, and p ≤ 0.05 was considered statistically significant.

Results

Characteristics of the study population

In total, 46 patients were included and started VLED treatment, whereof five patients (11%) dropped out before the 6 months visit (at the beginning of the VLED treatment, one cancelled participation and one was excluded due to depression, after 3 months two cancelled participation and one was excluded due to pregnancy).

A total of 41 patients completed the study, 63% women. The median baseline age was 54 (IQR 48–62) years. The characteristics of the study population are shown in Table 1.

Table 1 Characteristics of the 41 patients with PsA and obesity included in the study
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The association between BMI and disease activity at baseline

At baseline BMI was positively correlated with several measures of disease activity and function including DAS28CRP, DAPSA, tender joints count, CRP, patient’s global health VAS, Leeds enthesitis index and HAQ (Spearman’s rho ranged from rS = 0.312, p = 0.047 to rS = 0.483, p = 0.001) (Table 2).

Table 2 The correlation between BMI and disease activity and function at baseline in patients with PsA and obesity (N = 41)
Full size table

Weight loss and waist circumference

All the patients lost weight, from a minimum of 8.5 to a maximum of 40.2 kg. The median weight loss from baseline to the 6 months visit was 18.7 kg (IQR 14.6–26.5), corresponding to a loss of in median 18.6% (IQR 14.7–26.3) or min–max range 8–35% of baseline weight. BMI decreased from median 35.2 kg/m2 (IQR 34.1–38.1) to 29.7 kg/m2 (IQR 26.2–31.5) (p < 0.001) and waistline circumference was reduced from median 116 cm (IQR 112–122) to 95.5 cm (89–103) (p < 0.001).

Change in disease activity

A significant reduction was seen in a majority of the disease activity measures at the 6 months visit (Table 3). The percentage of patients with MDA (primary endpoint) increased from 29.3% (n = 12) at baseline to 53.7% (n = 22) at 6 months (p = 0.002). Regarding the secondary endpoints, PSARC was reached by 46.3% (n = 19) of the patients and ACR 20, 50 and 70 responses by 51.2% (n = 21), 34.1% (n = 14) and 7.3% (n = 3) respectively (Fig. 1).

Table 3 Disease activity and function before and after weight loss treatment in 41 patients with PsA
Full size table
Fig. 1
figure 1

The percentage of patients reaching American College of Rheumatology (ACR) 20, ACR 50 and ACR 70 response criteria, Psoriatic Arthritis Response Criteria (PsARC) and Minimal Disease Activity (MDA). BL, baseline; M6, 6 months visit

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The distributions of BSA, DAS28CRP, DAPSA and HAQ at baseline and the three- and six-months visits are shown in Fig. 2. The improvement of the skin occurred later than for the other disease activity parameters. Five patients (12%) experienced a flare in their psoriatic lesions at the 3 months visit. Six patients (15%) had a worsening of joint disease defined as an increase in DAPSA score (range + 1.9–9.1) at the 6 months visit. The laboratory parameters haemoglobin, CRP and PLT all declined significantly, compared with baseline.

Fig. 2
figure 2

Boxplots showing the distributions at baseline and the 3 and 6 months visits of a psoriatic body surface area (BSA), b Disease Activity in PSoriatic Arthritis (DAPSA), c Disease Activity Score using 28 joint counts based on CRP (DAS28CRP) and d Health Assessment Questionnaire (HAQ)

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A sub-analysis on the 29 patients who did not already have MDA at baseline, showed that PsARC was reached by 51.7% (n = 14) and ACR 20, 50 and 70 response by 62.1% (n = 18), 37.9% (n = 11) and 6.9% (n = 2) respectively of patients in this group. Disease activity and function before and after weight loss treatment in patients who did not have MDA at baseline is displayed in Additional file 1: Table S1.

Improvement of disease activity in relation to grade of weight loss

The weight loss in percentage of baseline weight was positively correlated with Δ-DAS28CRP (rS = 0.464; p = 0.002) and Δ-HAQ (rS = 0.376; p = 0.015), but not with other Δ-values of disease activity. In addition, the ACR 20 response rate was significantly higher in patients with a weight loss ≥ median 18.6% (n = 21) compared with < 18.6% (n = 20) (ACR 20 71% vs 30%; p = 0.008). Similarly, a trend towards higher ACR 50 response rate was observed in patients with a weight loss ≥ 18.6% compared with < 18.6% (ACR 50 48% vs 20%; p = 0.062). The percentage reduction in waist circumference was also significantly correlated with the reduction in DAS28CRP (Δ-value) (rS = 0.374; p = 0.019).

Side effects and the patients’ experiences of the VLED treatment

The treatment was generally well tolerated. Some patients experienced obstipation, freezing, loss of hair and hypotension during the strict VLED period and 12% a flare in psoriasis as previously mentioned. No serious adverse events occurred. When asked to score their experience of the VLED treatment between 1 (very easy to implement) and 10 (very hard to implement), the median score was 2 (IQR 1–3.5). When asked to score their experience of the VLED treatment in comparison to what they had expected, 83% (n = 34) answered “much easier than expected” or “easier than expected”. The patients generally scored their experience of the transition from VLED to normal food as harder. The median score was 4 (IQR 2–6) and totally 56% (n = 23) answered “as expected” or “harder than expected” (Fig. 3).

Fig. 3
figure 3

The patients’ experience of the very low energy diet (VLED) treatment and the transition from VLED to normal food

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Discussion

This study aimed to prospectively investigate the association between VLED weight loss treatment and disease activity in patients with PsA and obesity. We found significant improvement of the disease activity in joints, entheses and skin, reduction of CRP, PLT and parameters assessing function at the 6 months follow-up. The primary endpoint, patients with MDA, increased from 29.3% at baseline to 53.7% at 6 months (p = 0.002). PSARC was reached by 46% of the patients, and the ACR 20, 50 and 70 responses were 51%, 34% and 7% respectively. As a comparison, randomized controlled trials of TNF inhibitors on PsA have typically reported ACR 20 and 50 responses of 50–60% and 30–40% respectively, whereas the reported ACR 20 and 50 responses to placebo have been 15–25% and 0–5% [31, 32]. Reduction in weight correlated in a dose-response manner with higher ACR 20 response rate and greater reductions in DAS28CRP and HAQ. The treatment which resulted in a substantial weight loss of in median 18.6% of the baseline weight was well tolerated with only few and mild side effects and was perceived as feasible by a majority of the patients. Further, we found that a higher BMI at baseline was associated with increased disease activity and poorer self-reported function. The present study thus supports the hypothesis that obesity is a promotor of disease activity in PsA.

The mechanisms linking PsA occurrence and disease activity with obesity has not been fully clarified. Both immunological, biomechanical and behavioural mechanisms are likely to be involved in the interplay between PsA and obesity. PsA, obesity and atherosclerosis are conditions characterized by chronic inflammation, mediated via partly common immunologic pathways. Tumour necrosis factor α (TNFα), interleukin (IL)23, IL17, IL6 and IL1β are all key cytokines in the pathogenesis of PsA. The white adipose tissue (WAT) can produce the same cytokines (TNFα, IL-23, IL-17, IL-6, IL-1β) in addition to both pro-inflammatory adipokines (resistin, fetuin-A, chemerin, leptin) and adipokines viewed as primarily anti-inflammatory (adiponektin, omentin) [33]. In obese individuals, WAT is infiltrated by immune cells, such as M1-type macrophages, dendritic cells, IL17 producing T-lymphocytes (Th17) and B-lymphocytes [34]. Moreover, in obesity, there is a persistent over-production of the pro-inflammatory cytokines and adipokines, which may fuel the autoimmune inflammation in PsA [34, 35]. Interestingly, there is also evidence that localized inflammation in fat pads inside joints, juxta-posed to entheses and underneath psoriatic skin lesions may play a local pathophysiological role in PsA and psoriasis [36]. Elevated levels of leptin and resistin and lower levels of adiponectin in serum adjusted for BMI have been shown in patients with PsA and psoriasis in comparison with healthy controls. Elevated serum leptin and resistin have also been associated with an increased burden of skin and joint inflammation [37, 38].

Biomechanical stress may be another factor linking obesity with PsA. PsA is characterized by enthesitis, which is a chronic inflammation at attachment sites of tendons and ligaments, anatomical locations often subject to mechanical stress [39]. The weight load of obesity leads to both increased mechanical stress and risk of local microdamage. In the general population, obesity is also associated with pathology of entheses and tendons, in both upper and lower extremities [40]. In PsA, repeated occupational lifting of heavy loads and exposure to injury or bone fracture has been associated with onset of inflammatory arthritis in subjects with psoriasis [41, 42]. Psoriasis is also known to develop at sites of trauma, the so-called Köbner response [43]. Studies on animal models for spondyloarthritis (TNFΔARE and DBA/1 mice) have provided further proof for the importance of mechanical stress, by showing that unloading of the hind limb or tail suspension prohibited enthesitis and new bone formation in these mice [44].

Behavioural factors can also be a link between PsA and obesity. Pain and skin disease can induce a vicious cycle of lowered physical activity and over-eating, leading to obesity and further reduction of the mobility and physical activity [8, 45]. Efficient weight loss treatment could help reverse this process. Patients with PsA are at increased risk of developing CV and thromboembolic disease [12, 13]. In addition, obesity has been shown to be associated with poorer response and adherence to TNF inhibitor therapy [17, 46]. We recommend that weight loss treatment should be considered as complementary to pharmacological treatment in patients with PsA and obesity, since weight loss may improve both disease activity, effect of drug treatment and CV risk profile.

The reduced disease activity seen in the PsA patients after the VLED treatment in the present study could be due to a combination of mechanisms: metabolic effects associated with dietary energy restriction, reduction of pro-inflammatory mediators produced by the WAT, reduced loading of joints and entheses, especially in the back and lower limbs and reduced pain sensitivity. In situations of negative energy balance cells switch to utilize non-hepatic glucose, ketone bodies and free fatty acids as energy source [47]. This has a dampening and pro-apoptotic effect on activated T lymphocytes, which primarily depend on aerobic glycolysis [48]. Energy restriction and weight loss is also associated with increased levels of glucocorticoids and adiponectin and reduced levels of IL-6, TNFα and leptin in serum [49, 50]. In the current study, a negative energy balance was mainly present during the 12–16 weeks of strict VLED treatment. After this time point, only six patients (15%) had a further weight loss, whereas the rest of the patients had an increase in weight between the 3 and 6 months visits, indicative of a positive energy balance. The patients will be followed for 2 years to determine the relation between BMI and disease activity when the patients are no longer in a hypocaloric condition.

Obesity is associated with increased pain sensitivity in inflammatory rheumatic diseases, osteoarthritis and fibromyalgia [45]. In the current study, the change in composite scores for disease activity after weight loss was mainly driven by a reduction in the number of tender joints and entheses and by lowered patients’ VAS for pain and global disease activity, although there was also a reduction in parameters reflecting inflammation, such as CRP, PLT, swollen joints count and BSA.

There is one prior study which has prospectively studied the effects of weight loss in patients with PsA and obesity or overweight starting treatment with a TNF-inhibitor. After 6 months treatment, the patients with a successful weight loss (≥ 5%) had a higher rate of achieving MDA than those without a successful weight loss (MDA 50% vs 23%; p < 0.001) [17]. The patients had higher disease activity at baseline than in the present study, but the weight loss, which was achieved by a hypocaloric diet, was lower. One earlier randomized trial studied the effects of low-energy diet (LED) treatment (800–1000 kcal/day) compared with an ordinary healthy all-round diet in patients with psoriasis and obesity (30 vs. 30) and reported improvement of DLQI and cardiovascular risk profile in the LED arm, but only a trend towards improvement of Psoriasis Area and Severity Index (PASI) after 16 weeks. The weight loss was however correlated with the reduction of PASI. The beneficial effects were sustained at 64 weeks follow-up [51, 52]. Positive effects on psoriasis have also been reported retrospectively by patients after bariatric surgery in earlier studies [53, 54].

There are some limitations of the study. First, the present study lacks a control group. The success of the weight loss treatment is reliant on the patients’ determination to follow the given instructions and refrain from intake of energy-containing foods and beverages other than the VLED and non-caloric beverages during the initial strict period of 12–16 weeks. To be effective, VLED treatment must be based on the patients’ active decision and randomization between VLED and care-as-usual was therefore considered unsuitable. Second, no blinding of the assessors was made. Third, a high disease activity was not an inclusion criterion of the study, which may have affected the results. In fact, 29% of the patients had already MDA at baseline. Nevertheless, the study was able to show significant association between weight loss and reduced disease activity. Fourth, no documentation of the side effects (obstipation, freezing, loss of hair and hypotension) was done; hence, no exact data on the occurrence can be presented. No serious adverse event occurred however during the study. Fifth, the study was relatively short in duration, and it is indeed a great challenge to achieve long-term weight loss. The patients will however be followed during 24 months.

Strengths of the present study are the prospective design and the powerful intervention that resulted in a substantial weight loss due to excellent adherence to the dietary regime. The study demonstrates that adding a weight loss treatment to the conventional pharmacologic treatment in patients with PsA and obesity may lead to benefits including lowering of several measures of disease activity along with the weight reduction.

Conclusions

Weight loss treatment with VLED in patients with PsA and obesity was associated with significant improvement of disease activity in joints, entheses and skin at 6 months follow-up. A larger weight loss resulted in more improvement in a dose-response manner. The treatment was effective, safe and well tolerated. In addition, we could demonstrate association between higher BMI and increased disease activity at baseline. The patients will be followed during 24 months to study long-term treatment effects. The study supports the hypothesis that obesity is involved in the pathophysiology of PsA.

Abbreviations

ACR:

American College of Rheumatology

BMI:

Body mass index

BSA:

Body surface area

CASPAR:

Classification for Psoriatic Arthritis

CRP:

C-reactive protein

cs/b DMARD:

Conventional synthetic/biologic disease modifying anti-rheumatic drug

CV:

Cardiovascular

DAPSA:

Disease Activity in PSoriatic Arthritis

DAS28CRP:

Disease Activity Score using 28 joint counts based on CRP

DLQI:

Dermatology Life Quality Index

ESR:

Erythrocyte sedimentation rate

HAQ:

Health Assessment Questionnaire

Hb:

Haemoglobin

IL:

Interleukin

IQR:

Interquartile range

MDA:

Minimal disease activity

MetS:

Metabolic syndrome

NSAID:

Non-steroidal anti-inflammatory drug

PLT:

Platelet count

PsA:

Psoriatic arthritis

PsARC:

Psoriatic Arthritis Response Criteria

r S :

Spearman’s correlation

TNFi:

Tumour necrosis factor inhibitor

TNFα:

Tumour necrosis factor α

VAS:

Visual analogue scale

VLED:

Very low energy diet

WAT:

White adipose tissue

WBC:

White blood cell count

References

  1. Ritchlin CT, Colbert RA, Gladman DD. Psoriatic arthritis. N Engl J Med. 2017;376(21):2095–6.

    PubMed  Google Scholar 

  2. Labitigan M, Bahce-Altuntas A, Kremer JM, Reed G, Greenberg JD, Jordan N, Putterman C, Broder A. Higher rates and clustering of abnormal lipids, obesity, and diabetes mellitus in psoriatic arthritis compared with rheumatoid arthritis. Arthritis Care Res (Hoboken). 2014;66(4):600–7.

    Article  CAS  Google Scholar 

  3. Haroon M, Gallagher P, Heffernan E, FitzGerald O. High prevalence of metabolic syndrome and of insulin resistance in psoriatic arthritis is associated with the severity of underlying disease. J Rheumatol. 2014;41(7):1357–65.

    Article  Google Scholar 

  4. Bostoen J, Van Praet L, Brochez L, Mielants H, Lambert J. A cross-sectional study on the prevalence of metabolic syndrome in psoriasis compared to psoriatic arthritis. J Eur Acad Dermatol Venereol. 2014;28(4):507–11.

    Article  CAS  Google Scholar 

  5. Eder L, Harvey P, Chandran V, Rosen CF, Dutz J, Elder JT, Rahman P, Ritchlin CT, Rohekar S, Hayday R, et al. Gaps in diagnosis and treatment of cardiovascular risk factors in patients with psoriatic disease: an international multicenter study. J Rheumatol. 2018;45(3):378–84.

    Article  Google Scholar 

  6. Li W, Han J, Qureshi AA. Obesity and risk of incident psoriatic arthritis in US women. Ann Rheum Dis. 2012;71(8):1267–72.

    Article  Google Scholar 

  7. Eder L, Thavaneswaran A, Chandran V, Cook RJ, Gladman DD. Obesity is associated with a lower probability of achieving sustained minimal disease activity state among patients with psoriatic arthritis. Ann Rheum Dis. 2015;74(5):813–7.

    Article  Google Scholar 

  8. Versini M, Jeandel PY, Rosenthal E, Shoenfeld Y. Obesity in autoimmune diseases: not a passive bystander. Autoimmun Rev. 2014;13(9):981–1000.

    Article  CAS  Google Scholar 

  9. Setty AR, Curhan G, Choi HK. Obesity, waist circumference, weight change, and the risk of psoriasis in women: nurses’ health study II. Arch Intern Med. 2007;167(15):1670–5.

    Article  Google Scholar 

  10. Galindez E, Carmona L. Is obesity in psoriatic arthritis associated with a poorer therapeutic response and more adverse effects of treatment with an anchor drug? Reumatol Clin. 2016;12(6):307–12.

    Article  Google Scholar 

  11. Jamnitski A, Symmons D, Peters MJ, Sattar N, McInnes I, Nurmohamed MT. Cardiovascular comorbidities in patients with psoriatic arthritis: a systematic review. Ann Rheum Dis. 2013;72(2):211–6.

    Article  Google Scholar 

  12. Bengtsson K, Forsblad-d'Elia H, Lie E, Klingberg E, Dehlin M, Exarchou S, Lindstrom U, Askling J, Jacobsson LTH. Are ankylosing spondylitis, psoriatic arthritis and undifferentiated spondyloarthritis associated with an increased risk of cardiovascular events? A prospective nationwide population-based cohort study. Arthritis Res Ther. 2017;19(1):102.

    Article  Google Scholar 

  13. Bengtsson K, Forsblad-d'Elia H, Lie E, Klingberg E, Dehlin M, Exarchou S, Lindström U, Askling J, Jacobsson LTH. Risk of cardiac rhythm disturbances and aortic regurgitation in different spondyloarthritis subtypes in comparison with general population: a register-based study from Sweden. Ann Rheum Dis. 2018;77(4):541-548. https://doi.org/10.1136/annrheumdis-2017-212189.

  14. Eder L, Chandran V, Gladman DD. The Framingham risk score underestimates the extent of subclinical atherosclerosis in patients with psoriatic disease. Ann Rheum Dis. 2014;73(11):1990–6.

    Article  Google Scholar 

  15. Eder L, Jayakar J, Shanmugarajah S, Thavaneswaran A, Pereira D, Chandran V, Rosen CF, Gladman DD. The burden of carotid artery plaques is higher in patients with psoriatic arthritis compared with those with psoriasis alone. Ann Rheum Dis. 2013;72(5):715–20.

    Article  Google Scholar 

  16. Eder L, Thavaneswaran A, Chandran V, Cook R, Gladman DD. Increased burden of inflammation over time is associated with the extent of atherosclerotic plaques in patients with psoriatic arthritis. Ann Rheum Dis. 2015;74(10):1830-5. https://doi.org/10.1136/annrheumdis-2014-205267.

  17. Di Minno MN, Peluso R, Iervolino S, Russolillo A, Lupoli R, Scarpa R. Weight loss and achievement of minimal disease activity in patients with psoriatic arthritis starting treatment with tumour necrosis factor alpha blockers. Ann Rheum Dis. 2014;73(6):1157–62.

    Article  Google Scholar 

  18. Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H, Group CS. Classification criteria for psoriatic arthritis: development of new criteria from a large international study. Arthritis Rheum. 2006;54(8):2665–73.

    Article  Google Scholar 

  19. Mustajoki P, Pekkarinen T. Very low energy diets in the treatment of obesity. Obes Rev. 2001;2(1):61–72.

    Article  CAS  Google Scholar 

  20. Lean M, Brosnahan N, McLoone P, McCombie L, Higgs AB, Ross H, Mackenzie M, Grieve E, Finer N, Reckless J, et al. Feasibility and indicative results from a 12-month low-energy liquid diet treatment and maintenance programme for severe obesity. Br J Gen Pract. 2013;63(607):e115–24.

    Article  Google Scholar 

  21. Healy PJ, Helliwell PS. Measuring clinical enthesitis in psoriatic arthritis: assessment of existing measures and development of an instrument specific to psoriatic arthritis. Arthritis Rheum. 2008;59(5):686–91.

    Article  Google Scholar 

  22. Bozek A, Reich A. The reliability of three psoriasis assessment tools: psoriasis area and severity index, body surface area and physician global assessment. Adv Clin Exp Med. 2017;26(5):851–6.

    Article  Google Scholar 

  23. Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)--a simple practical measure for routine clinical use. Clin Exp Dermatol. 1994;19(3):210–6.

    Article  CAS  Google Scholar 

  24. Fries JF, Spitz P, Kraines RG, Holman HR. Measurement of patient outcome in arthritis. Arthritis Rheum. 1980;23(2):137–45.

    Article  CAS  Google Scholar 

  25. Schoels M, Aletaha D, Funovits J, Kavanaugh A, Baker D, Smolen JS. Application of the DAREA/DAPSA score for assessment of disease activity in psoriatic arthritis. Ann Rheum Dis. 2010;69(8):1441–7.

    Article  Google Scholar 

  26. Prevoo ML, van ‘t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL. Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum. 1995;38(1):44–8.

    Article  CAS  Google Scholar 

  27. Coates LC, Fransen J, Helliwell PS. Defining minimal disease activity in psoriatic arthritis: a proposed objective target for treatment. Ann Rheum Dis. 2010;69(1):48–53.

    Article  CAS  Google Scholar 

  28. Clegg DO, Reda DJ, Weisman MH, Blackburn WD, Cush JJ, Cannon GW, Mahowald ML, Schumacher HR Jr, Taylor T, Budiman-Mak E, et al. Comparison of sulfasalazine and placebo in the treatment of ankylosing spondylitis. A Department of Veterans Affairs Cooperative Study. Arthritis Rheum. 1996;39(12):2004–12.

    Article  CAS  Google Scholar 

  29. Fransen J, Antoni C, Mease PJ, Uter W, Kavanaugh A, Kalden JR, Van Riel PL. Performance of response criteria for assessing peripheral arthritis in patients with psoriatic arthritis: analysis of data from randomised controlled trials of two tumour necrosis factor inhibitors. Ann Rheum Dis. 2006;65(10):1373–8.

    Article  CAS  Google Scholar 

  30. Felson DT, Anderson JJ, Boers M, Bombardier C, Furst D, Goldsmith C, Katz LM, Lightfoot R Jr, Paulus H, Strand V, et al. American College of Rheumatology. Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum. 1995;38(6):727–35.

    Article  CAS  Google Scholar 

  31. Mease PJ, Kivitz AJ, Burch FX, Siegel EL, Cohen SB, Ory P, Salonen D, Rubenstein J, Sharp JT, Tsuji W. Etanercept treatment of psoriatic arthritis: safety, efficacy, and effect on disease progression. Arthritis Rheum. 2004;50(7):2264–72.

    Article  CAS  Google Scholar 

  32. Antoni C, Krueger GG, de Vlam K, Birbara C, Beutler A, Guzzo C, Zhou B, Dooley LT, Kavanaugh A, Investigators IT. Infliximab improves signs and symptoms of psoriatic arthritis: results of the IMPACT 2 trial. Ann Rheum Dis. 2005;64(8):1150–7.

    Article  CAS  Google Scholar 

  33. Wolk K, Sabat R. Adipokines in psoriasis: an important link between skin inflammation and metabolic alterations. Rev Endocr Metab Disord. 2016;17(3):305–17.

    Article  CAS  Google Scholar 

  34. Ivanov S, Merlin J, Lee MKS, Murphy AJ, Guinamard RR. Biology and function of adipose tissue macrophages, dendritic cells and B cells. Atherosclerosis. 2018;271:102–10.

    Article  CAS  Google Scholar 

  35. Chehimi M, Vidal H, Eljaafari A. Pathogenic role of IL-17-producing immune cells in obesity, and related inflammatory diseases. J Clin Med. 2017;6(7).

  36. Kruglikov IL, Wollina U. Local effects of adipose tissue in psoriasis and psoriatic arthritis. Psoriasis (Auckl). 2017;7:17–25.

    CAS  Google Scholar 

  37. Eder L, Jayakar J, Pollock R, Pellett F, Thavaneswaran A, Chandran V, Rosen CF, Gladman DD. Serum adipokines in patients with psoriatic arthritis and psoriasis alone and their correlation with disease activity. Ann Rheum Dis. 2013;72(12):1956–61.

    Article  CAS  Google Scholar 

  38. Xue Y, Jiang L, Cheng Q, Chen H, Yu Y, Lin Y, Yang X, Kong N, Zhu X, Xu X, et al. Adipokines in psoriatic arthritis patients: the correlations with osteoclast precursors and bone erosions. PLoS One. 2012;7(10):e46740.

    Article  CAS  Google Scholar 

  39. McGonagle DG, Helliwell P, Veale D. Enthesitis in psoriatic disease. Dermatology. 2012;225(2):100–9.

    Article  Google Scholar 

  40. Scott A, Zwerver J, Grewal N, de Sa A, Alktebi T, Granville DJ, Hart DA. Lipids, adiposity and tendinopathy: is there a mechanistic link? Critical review. Br J Sports Med. 2015;49(15):984–8.

    Article  Google Scholar 

  41. Pattison E, Harrison BJ, Griffiths CE, Silman AJ, Bruce IN. Environmental risk factors for the development of psoriatic arthritis: results from a case-control study. Ann Rheum Dis. 2008;67(5):672–6.

    Article  CAS  Google Scholar 

  42. Eder L, Shanmugarajah S, Thavaneswaran A, Chandran V, Rosen CF, Cook RJ, Gladman DD. The association between smoking and the development of psoriatic arthritis among psoriasis patients. Ann Rheum Dis. 2012;71(2):219–24.

    Article  Google Scholar 

  43. Melski JW, Bernhard JD, Stern RS. The Koebner (isomorphic) response in psoriasis. Associations with early age at onset and multiple previous therapies. Arch Dermatol. 1983;119(8):655–9.

    Article  CAS  Google Scholar 

  44. Jacques P, Lambrecht S, Verheugen E, Pauwels E, Kollias G, Armaka M, Verhoye M, Van der Linden A, Achten R, Lories RJ, et al. Proof of concept: enthesitis and new bone formation in spondyloarthritis are driven by mechanical strain and stromal cells. Ann Rheum Dis. 2014;73(2):437–45.

    Article  Google Scholar 

  45. Arranz LI, Rafecas M, Alegre C. Effects of obesity on function and quality of life in chronic pain conditions. Curr Rheumatol Rep. 2014;16(1):390.

    Article  Google Scholar 

  46. Hojgaard P, Glintborg B, Kristensen LE, Gudbjornsson B, Love TJ, Dreyer L. The influence of obesity on response to tumour necrosis factor-alpha inhibitors in psoriatic arthritis: results from the DANBIO and ICEBIO registries. Rheumatology (Oxford). 2016;55(12):2191–9.

    Article  Google Scholar 

  47. Longo VD, Mattson MP. Fasting: molecular mechanisms and clinical applications. Cell Metab. 2014;19(2):181–92.

    Article  CAS  Google Scholar 

  48. Choi IY, Lee C, Longo VD. Nutrition and fasting mimicking diets in the prevention and treatment of autoimmune diseases and immunosenescence. Mol Cell Endocrinol. 2017;455:4–12.

    Article  CAS  Google Scholar 

  49. Piccio L, Stark JL, Cross AH. Chronic calorie restriction attenuates experimental autoimmune encephalomyelitis. J Leukoc Biol. 2008;84(4):940–8.

    Article  CAS  Google Scholar 

  50. Frikke-Schmidt H, O'Rourke RW, Lumeng CN, Sandoval DA, Seeley RJ. Does bariatric surgery improve adipose tissue function? Obes Rev. 2016;17(9):795–809.

    Article  CAS  Google Scholar 

  51. Jensen P, Christensen R, Zachariae C, Geiker NR, Schaadt BK, Stender S, Hansen PR, Astrup A, Skov L. Long-term effects of weight reduction on the severity of psoriasis in a cohort derived from a randomized trial: a prospective observational follow-up study. Am J Clin Nutr. 2016;104(2):259–65.

    Article  CAS  Google Scholar 

  52. Jensen P, Zachariae C, Christensen R, Geiker NR, Schaadt BK, Stender S, Hansen PR, Astrup A, Skov L. Effect of weight loss on the severity of psoriasis: a randomized clinical study. JAMA Dermatol. 2013;149(7):795–801.

    Article  Google Scholar 

  53. Farias MM, Achurra P, Boza C, Vega A, de la Cruz C. Psoriasis following bariatric surgery: clinical evolution and impact on quality of life on 10 patients. Obes Surg. 2012;22(6):877–80.

    Article  CAS  Google Scholar 

  54. Hossler EW, Wood GC, Still CD, Mowad CM, Maroon MS. The effect of weight loss surgery on the severity of psoriasis. Br J Dermatol. 2013;168(3):660–1.

    Article  CAS  Google Scholar 

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Acknowledgements

We wish to thank all the patients who participated in the study. We also wish to thank Anneli Lund and Marie-Louise Andersson at the Clinical Rheumatology Research Center at Sahlgrenska University Hospital and the personnel at the Obesity Unit at Sahlgrenska University Hospital.

Funding

This work was supported by grants from the Swedish state under the agreement between the Swedish Government and the county councils, the ALF-agreement (ALFGBG-825511), the Health and Medical Care Executive Board of the Västra Götaland, the Gothenburg Society of Medicine, Inger Bendix foundation for medical research, Rune and Ulla Amlövs foundation for Rheumatology Research, Stiftelsen Psoriasisfonden and the Swedish Rheumatology Association research grant in collaboration with Roche.

Availability of data and materials

The datasets analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

    Eva Klingberg, Lennart Jacobsson, Helena Forsblad-d’Elia & Hans Carlsten

  2. Institute of Neuroscience and Physiology, Section of Health and Rehabilitation, Physiotherapy, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

    Annelie Bilberg

  3. Department of Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

    Sofia Björkman & Ingrid Larsson

  4. Department of Rheumatology, Hospital of Borås, Borås, Sweden

    Martin Hedberg

  5. Department of Public Health and Clinical Medicine, Rheumatology, Umeå University, Umeå, Sweden

    Helena Forsblad-d’Elia

  6. Department of Medicine, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden

    Björn Eliasson

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  1. Eva Klingberg
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Contributions

EK was responsible for the study design, recruitment of patients, rheumatologic evaluations, data collection, statistical analyses and drafting of the article. AB participated in the study design, recruitment and examination of patients, collection, analysis and interpretation of data. SF participated in recruitment and examination of patients, weight loss treatment and follow-up, collection and interpretation of data. MH participated in the recruitment and rheumatologic evaluation of the patients and collection of data. LJ participated in the study design, analysis and interpretation of data. HF participated in the study design, analysis and interpretation of data. HC participated the study design, analysis and interpretation of data. BE participated in the study design, recruitment and examination of patients, collection and interpretation of data and was responsible for the weight loss treatment and follow-up. IL participated in the study design, recruitment and examination of patients, collection and interpretation of data and was responsible for the weight loss treatment and follow-up. All authors have critically reviewed the manuscript, approved the final version to be published and agreed to be accountable for all aspects of the work.

Corresponding author

Correspondence to Eva Klingberg.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the Regional Ethics Committee in Gothenburg and carried out in accordance with the Helsinki declaration. All participants gave their written informed consent.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no financial or nonfinancial competing interests. The patients were able to buy the VLED at a reduced price from Cambridge Weight Plan Limited, Solna, Sweden.

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Additional file

Additional file 1:

Table S1. Disease activity and function before and after weight loss treatment in the 29 patients with PsA who did not have minimal disease activity at baseline. (DOCX 16 kb)

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Klingberg, E., Bilberg, A., Björkman, S. et al. Weight loss improves disease activity in patients with psoriatic arthritis and obesity: an interventional study. Arthritis Res Ther 21, 17 (2019). https://doi.org/10.1186/s13075-019-1810-5

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Keywords

  • Psoriatic arthritis
  • Psoriasis
  • Obesity
  • Metabolic syndrome
  • Weight loss
  • VLED
  • Cardiovascular disease

Arthritis Research & Therapy

ISSN: 1478-6362

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