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Background To explore the effect of abatacept treatment on patient-reported outcomes (PROs) in psoriatic arthritis (PsA). Methods Patients with PsA were randomised (1:1) to subcutaneous abatacept 125 mg weekly/placebo for 24 weeks with early escape (EE) to open-label abatacept (week 16). Adjusted mean changes from baseline to weeks 16 (all patients) and 24 (non-EE responders) in Health Assessment Questionnaire-Disability Index (HAQ-DI), Short Form-36 (SF-36; physical and mental component summary and domains), Dermatology Life Quality Index and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated. Subpopulations were analysed by baseline C-reactive protein (CRP) level (> vs ≤ upper limit of normal [ULN]) and prior tumour necrosis factor inhibitor (TNFi) exposure. Proportions of patients reporting improvements ≥ minimal clinically important differences (MCIDs) and ≥ normative values (NVs) in HAQ-DI, SF-36 and FACIT-F (week 16 before EE) were analysed. Results In total population, numerically higher improvements in most PROs were reported with abatacept (n = 213) versus placebo (n = 211) at both time points (P > 0.05). Higher proportions of abatacept versus placebo patients reported PRO improvements ≥ MCID and ≥ NV at week 16. At week 16, all PRO improvements were numerically greater (P > 0.05) in patients with baseline CRP > ULN versus CRP ≤ ULN (all significant [95% confidence interval] for abatacept vs placebo); improvements in SF-36 component summaries and FACIT-F were greater in TNFi-naïve versus TNFi-exposed patients (abatacept > placebo). Week 24 subgroup data were difficult to interpret due to low patient numbers. Conclusions Abatacept treatment improved PROs in patients with PsA versus placebo, with better results in elevated baseline CRP and TNFi-naïve subpopulations. Trial registration ClinicalTrials.gov number, NCT01860976 (funded by Bristol-Myers Squibb); date of registration: 23 May 2013. Electronic supplementary material The online version of this article (10.1186/s13075-018-1769-7) contains supplementary material, which is available to authorized users.

Mast cell-deficient W/Wv mice are resistant to K/BxN serum transfer arthritis, and this resistance may be overcome by engraftment with mast cells. However, the pathways by which mast cells participate in arthritis remain unknown. Using a candidate mediator approach, we explored IL-1 as a potentially key mediator by which mast cells promote arthritis. As expected, IL-1α/β-deficient mice were completely resistant to arthritis. Short-term administration of exogenous IL-1 restored an attenuated arthritis course in these animals, consistent with an ongoing requirement for IL-1. Surprisingly, deficient W/Wv mice treated with IL-1 at disease induction displayed a full normal course of arthritis, demonstrating that exogenous IL-1 can bypass the need for mast cells. TNF proved unable to exert a similar effect. We therefore engrafted IL-1-/- bone marrow-derived mast cells (BMMC) into W/Wv animals and found that these animals displayed resistance to arthritis equivalent to nonengrafted W/Wv mice, consistent with an obligate role for IL-1 of mast cell origin. Exploring further the mechanisms by which mast cells may become activated in this IgG1-driven model, we found that BMMC stimulated in vitro via FcγRIII elaborated IL-1, while BMMC lacking this receptor were unable to mediate arthritis upon engraftment into W/Wv recipients. While BMMC engrafted into W/Wv animals disproportionately populate the spleen, we excluded a contribution from this aphysiologic mast cell population via splenectomy and by documenting that systemic levels of IL-1 were not detectable during arthritis initiation in engrafted animals. We conclude that mast cells local to the joint and activated via FcγRIII promote K/BxN serum transfer arthritis by production of IL-1, an activity that appears delimited to the initiation of disease (the 'jump start').