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Background: Obesity is overrepresented in patients with psoriatic arthritis (PsA) and associated with higher disease activity, poorer effect of treatment, and increased cardiovascular morbidity. However, studies on the effects of weight loss are needed. This study aimed to prospectively study the effects of weight loss treatment with a very low energy diet (VLED) on disease activity in patients with PsA (CASPAR criteria) and obesity (body mass index [BMI≥33kg/m2). Methods: VLED (640kcal/day) was taken for 12 to 16 weeks, depending on pretreatment BMI. Afterward, 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 antirheumatic drugs was held constant from three months before, until six months after baseline. Patients were assessed with BMI, 66/68 joints count, Leeds enthesitis index, psoriasis body surface area (BSA), questionnaires, and C-reactive protein (CRP) at baseline, three, and six 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: In total, 41 of 46 patients completed the study, 63 percent of whom were women, with a median age of 54 years (interquartile range [IQR] 48-62). At baseline, increased BMI was associated with higher disease activity and poorer function. The median weight loss was 18.7kg (IQR 14.6-26.5) or 18.6 percent (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, Health Assessment Questionnaire (HAQ) and patient Visual Analogue Scale (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 percent, (p=0.002). PsARC was reached by 46.3 percent of patients. The ACR 20, 50 and 70 responses were 51.2, 34.1, and 7.3 percent of patients, respectively. Conclusion: 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. [ABSTRACT FROM AUTHOR]