In this prospective, open intervention study, we analysed the long-term effects of weight loss on disease activity, self-reported physical function and variables associated with the MetS in patients with PsA and obesity. After 12 months of structured weight loss treatment, a median weight reduction of 16% was associated with improvement of a majority of disease activity measures compared to baseline, including swollen/tender joints count, enthesitis, extent of psoriasis, CRP, HAQ, BASFI and VAS global health and fatigue. After 24 months, all patients had regained some weight, but a significant improvement could still be shown in swollen/tender joints count, enthesitis, CRP and HAQ, compared to baseline. Additionally, several variables of the MetS, such as waist circumference, HDL, TG, were significantly improved after 12 and 24 months, and some patients were able to stop anti-hypertensive treatment. The results of the study support the hypothesis of obesity as a promotor of disease activity in PsA, showing what could be attained by adding a weight loss program to routine medical care in patients with PsA and obesity.
In the present study the weight loss treatment with VLED was judged as easy to implement by most patients, but the transition from VLED to normal food was perceived as harder. A substantial weight reduction was noted during the VLED treatment, but as expected the patients started to gain weight already at six months. The patients were given an energy-reduced dietary advice and were instructed to engage in health-enhancing physical activity at least 150 minutes per week, but no follow up was made between 12- and 24-month visits. At the 24-month visit 40% still had a weight reduction of 10% or more compared to baseline in the present study. Several studies in both specialist and primary care have included VLED as part of a structured weight loss program for subjects with severe obesity and have shown clinically meaningful weight loss, and the results of the present study are comparable with those.[32–36] Given the difficulties to treat obesity in a longer perspective once it is established, more attention should be given to prevent weight gain and the development of obesity in patients with psoriasis and PsA. We propose that the patients should be informed about the unfavourable effects of obesity on disease course and cardiovascular risk during patient educational programs and that body weight should be routinely measured and discussed during medical follow-ups. We also argue that patients with overweight should aim for weight maintenance and patients with obesity should be offered a weight loss program and be encouraged to participate in health-enhancing physical activity throughout the disease course.
Totally six patients were lost to follow-up between the six- and 24-month visits. It is possible that the patients who did not come to follow-up had a poorer weight maintenance than the patients who continued in the study.
Studies on the effects of weight loss on disease activity in PsA are scares, but there are a few studies on psoriasis. Effect on disease severity in psoriasis has been shown after weight loss by bariatric surgery [37, 38] and dietary interventions [39–42]. Improved response to cyclosporine  and TNFi  has also been shown in psoriasis after weight loss. Additionally, bariatric surgery in obesity has been associated with a lower future risk of developing psoriasis in one study , and psoriasis and PsA in another study. One prior randomized controlled study on dietary interventions in patients with PsA and overweight or obesity starting treatment with TNFi demonstrated that a weight loss of ≥ 5% increased the chance of reaching MDA at six months follow-up. The odds ratio (OR) for achieving MDA at a weight loss 5–10% and > 10% was 3.75 (95% CI 1.36–10.36) and 6.67 (95% CI 2.41–18.41) respectively.
Obesity is a pro-inflammatory state, where the adipose tissue is invaded by activated M1-type macrophages and B- and T-lymphocytes, with an over-production of cytokines, such as tumour necrosis factor-a (TNFa) and interleukin (IL)1, IL6, IL17 and IL23, which are all involved in the pathogenesis of psoriasis and PsA.[48, 49] Moreover, pro-inflammatory adipokines (resistin, fetuin-A, chemerin, leptin) are over-expressed in the adipocytes in obesity and adipokines with mainly anti-inflammatory effects (adiponektin, omentin) are supressed. In the present study we show sustained lowered disease activity at the 12- and 24-month visits, when the patients were unlikely to be affected by the severe initial energy restriction from VLED, although the majority of participants had kept, to a different degree, an energy reduced diet. The anti-inflammatory effect of the weight loss may rather be explained by decreased production of pro-inflammatory cytokines and adipokines by the adipose tissue. Lowered mechanical loading by weight loss and less risk of microdamage, enthesitis and arthritis could also be explanatory factors.
In the present study, weight loss was associated with a reduction of other cardiovascular risk factors such as hypertension and dyslipidemia, and additionally lowered levels of blood glucose and HbA1c. MetS is defined as a set of cardiovascular risk factors that cluster together; enlarged waist circumference, high blood glucose levels, elevated blood pressure and TG, and reduced HDL. Insulin resistance, central obesity and overabundance of circulating fatty acid are suggested mechanisms underlying the MetS. The MetS is associated with increased mortality and poorer health outcomes in several aspects, such as a doubled risk of cardiovascular disease  and increased risk of various types of cancer . In psoriasis and PsA there is a clear overrepresentation of cardiovascular risk factors and of MetS [4, 14, 54, 55] and the patients are at higher risk of developing cardiovascular events.[5, 9] The present study shows that treatment of obesity entails both reduction in disease activity, possibly through reduction in pro-inflammatory state, as well as cardiovascular risk factor.
Patients with psoriasis and PsA are at increased risk of developing gout. In the present study weight loss was associated with a significant decrease in serum urate especially in the male patients. We could however not demonstrate any systematic correlation between the reduction in serum urate and the magnitude of weight loss, perhaps due to a small sample size and large interindividual weight change. Changes in dietary habits, including consumption of alcohol and sugar-sweetened soft drinks, may also have played a role in the reduction of serum urate.
Strengths and limitations
Strengths of the study are the prospective design with a long follow-up and the powerful intervention which resulted in a considerable weight loss.
There are also limitations of the present study to be acknowledged. Firstly, this is not a randomized controlled study and the absence of a control group is a major short-coming. Secondly, treatment with cs/bDMARDs was held constant from three month prior to baseline until the six-month visit, but change in cs/bDMARD treatment was allowed after the six-month visit, due to ethical reasons. We cannot exclude that change in treatment may have affected the results regarding disease activity at the 12- and 24-month visits. In the vast majority of patients, the medication with cs/bDMARDs was however held unchanged during the whole study period. Thirdly, pharmacological treatment against hypertension, hyperlipidemia and diabetes could not be held constant throughout the study, which may have affected levels of blood pressure, blood lipids and glucose metabolism during the follow-up. During the initial period with intense weight loss, some patients experienced hypotension and antihypertensive treatment had to be tapered.