All tophi with CR. Results: Among 212 patients randomized in the RCTs
All tophi with CR. Results: Among 212 patients randomized in the RCTs, 155 (73 ) had 1 tophus and 547 visible tophi were recorded at baseline. Overall tophus CR was recorded in 45 of patients in the biweekly group (P = 0.002 versus placebo), 26 in the monthly group, and 8 in the placebo group after six months of RCT therapy. TT-CR rates at six months were 28 , 19 , and 2 of tophi, respectively. Patients meeting the primary endpoint of sustained urate-lowering response to therapy (responders) were more likely than nonresponders to have an overall tophus CR at six months (54 vs 20 , respectively and 8 with placebo). Both overall tophus CR and TT-CRs increased with treatment duration in the OLE, reaching 70 (39/56) of patients and 55 (132/238) of target tophi after one year of treatment in patients receiving pegloticase during both the RCTs and OLE. At that time point, more tophi had resolved in responders (102/145 or 70 of tophi) than nonresponders (30/93; 32 ). Conclusions: Pegloticase reduced tophus burden in patients with refractory tophaceous gout, especially those achieving sustained urate-lowering. Complete resolution of tophi occurred in some patients by 13 weeks and in others with longer-term therapy. Trial registrations: NCT00325195, NCT* Correspondence: [email protected] 1 Center for Rheumatology Bone Research, 2730 University Blvd West, Wheaton, MD 20902, USA Full list of author information is ZM241385 mechanism of action available at the end of the article?2013 Baraf et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Baraf et al. Arthritis Research Therapy 2013, 15:R137 http://arthritis-research.com/content/15/5/RPage 2 ofIntroduction Refractory gout refers to the condition of a population of patients with symptomatic gout in whom treatment has failed to maintain a serum uric acid (SUA) level less than 6 mg/dl with oral urate-lowering therapies (ULTs) and appropriate medical management [1,2]. Patients with refractory gout are at risk for progressive urate crystal deposition disease, characterized by frequent attacks of acute gouty arthritis, gouty arthropathy and enlarging tophi, which are often associated with chronic pain, impairment of physical function and compromised healthrelated quality of life [1,3,4]. The tophus, a cardinal feature of chronic gout, is a mass of urate crystals embedded in fibrous and inflammatory tissue. Tophi contribute to gouty joint destruction and deformity and may undergo acute or chronic ulceration, erode adjacent bone, cause pressure effects on surrounding tissues and organs, interfere with joint function or become infected [1,5-9]. Once established, tophi do not regress or resolve unless the extracellular urate saturation that supports urate crystal deposition (reflected by hyperuricemia or SUA in excess of 6.8 mg/dl) is reversed and subsaturating urate levels are maintained. Achievement and maintenance of SUA in a range less than 6.0 mg for months to years does, however, promote dissolution PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/25962748 of urate crystal deposits and prevent further crystal deposition in tissues [10]. Rates of resolution of tophaceous deposits appear to be dependent on the extent of urate-lowering [11,12]. Furthermore, tracking the course of tophus size or number over time during treatm.
