Alipers using the diameter and the longest width perpendicular to the diameter. Response to treatment was categorized on the basis of change from baseline as complete response (CR; 100 decrease in area of the tophus), marked response (MR; 75 or greater to less than 100 decrease), partial response (PR; 50 or greater to less than 75 decrease), stable disease (SD; less than 50 decrease to less than 25 PX-478 web increase) and progressive disease (PD; 25 or greater increase). For each unmeasured target tophus, response to treatment was semiquantitatively assessed on the basis of the impression of the central reader, PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/29045898 and response was categorized as CR, improved, SD or PD. Tophus resolution was a secondary endpoint in the RCTs. The principal assessment was the proportion of patients achieving a tophus CR, defined as complete resolution of at least one tophus without development of new tophi or progressive enlargement of any other tophus. This measurement of a patient’s single overall best tophus response was intended to control for patients with multiple tophi and varying responses (Figure 1). If any new or progressing tophi were recorded at any time during the study, the final overall tophus response for that patient was PD. A second measure of tophus resolution was based on the total number of photographically identified baseline tophi. Target tophus CR (TT-CR) was defined as 100 decrease in the area of the tophus and is reported as the number or proportion of all baseline tophi with CR at the specific study visit.Statistical analysisThe two tophus assessment endpoints are presented as pooled data for the modified intent-to-treat (mITT) population in the RCTs, which comprised all randomized patients who received at least one dose of study medication and had at least one postdose observation. Only patients with tophi were included in these analyses (tophusevaluable population). The number or proportion of patients with overall best response of CR was compared for each pegloticase dosing group versus the placebo group using Fisher’s exact test. A similar analysis was applied to the number of tophi showing CR for the TT-CR endpoint. The overall tophus CR was further analyzed according to the patient’s PUA response, which was the predefined primary endpoint of the RCTs (lower than 6 mg/dl for 80 of the time during months 3 and 6).ResultsBaseline tophus statusThe mITT population included 212 patients with a mean gout duration of 15 years. From among theseBaraf et al. Arthritis Research Therapy 2013, 15:R137 http://arthritis-research.com/content/15/5/RPage 4 of003 25 mm 23 mmC61 mmTarget tophus outcomes for 4 tophi at 6 months Left knee 1 (A) CRD Left knee 2 (B) Right hand measurable (C) Right hand unmeasurable (D) PRPatient has 4 baseline tophi; 2 measurable on the knee (A and B), 1 measurable (C) and 1 unmeasurable (D) on the handCRSDA002 12 mm 20 mm 001 34 mmBest “overall” patient response is CR without new/progressing tophiBCal21 mm30 mmFigure 1 Illustration of a hypothetical patient showing the target tophus responses and overall tophus response. The diagram shows the tophus scoring system for a sample patient with four baseline tophi (three measurable and one unmeasurable). Tophus area was defined for each measurable tophus using the longest dimension and its perpendicular axis. The circle marks the unmeasurable tophus. Each baseline target tophus was rescored at all subsequent study visits. The patient illustrated in the figure had a best.
