Background: Biologic disease modifying anti-rheumatic drugs (bDMARDs) are recommended for radiographic axial spondyloarthritis (r-axSpA), otherwise known as ankylosing spondylitis, when conventional therapies fail. We report efficacy and safety results of a Phase 3 study of ixekizumab, a high-affinity monoclonal antibody that selectively targets IL-17A, in bDMARDnaïve patients with r-axSpA. Methods: In this randomized, double-blind, Phase 3 study, adult patients with inadequate response/intolerance to NSAIDs, an established diagnosis of r-axSpA, and with radiographic sacroiliitis centrally defined by modified New York criteria and ≥1 spondyloarthritis feature according to Assessment of Spondyloarthritis International Society (ASAS) criteria were recruited from 84 sites (12 countries) in Europe, Asia, and North America. Patients were randomized 1:1:1:1 using a computer-generated random sequence to 80 mg subcutaneous ixekizumab every two (Q2W) or four (Q4W) weeks, 40 mg adalimumab Q2W (active reference arm), or placebo. The primary endpoint was the proportion of patients achieving an ASAS40 response at Week 16. Findings: Between June 20, 2016 and August 22, 2017, 341 patients were randomized to placebo (N=87), adalimumab (N=90), ixekizumab Q2W (N=83), or ixekizumab Q4W (N=81). At Week 16, significantly more patients achieved ASAS40 with ixekizumab Q2W (n=43, 51•8%, p<0•0001), ixekizumab Q4W (n=39, 48•1%, p<0•0001), and adalimumab (n=32, 35•6%; p=0•0053) versus placebo (n=16, 18•4%). One serious infection occurred in each of the ixekizumab Q2W (1•2%), ixekizumab Q4W (1•2%), and adalimumab (1•1%) arms; none were reported with placebo. One (1•1%) Candida infection occurred in the adalimumab arm and one (1•2%) patient receiving ixekizumab Q2W was adjudicated as having probable Crohn's disease. No opportunistic infections, malignancies, or deaths occurred. Interpretation: Each dosing regimen of ixekizumab was superior to placebo for improving r-axSpA signs and symptoms in bDMARD-naïve patients; the safety profile was consistent with previous studies of ixekizumab. The adalimumab control arm performed as expected. Funding: Eli Lilly and Company Research in context Evidence before this study Pubmed was searched using the terms "ankylosing spondylitis", "axial spondyloarthritis", and "disease-modifying anti-rheumatic drugs", including articles through May 30, 2018. Axial spondyloarthritis (axSpA) is a chronic immune-mediated disease characterized by inflammation of the spine and sacroiliac joint (SIJ), peripheral joint involvement, extra articular manifestations, and a strong genetic association with human leukocyte antigen (HLA)-B27. Radiographic axSpA (r-axSpA) was previously classified as ankylosing spondylitis (AS) in 1984 and updated to r-axSpA as part of the ASAS criteria. Both criteria sets require the same radiographically confirmed structural damage to the sacroiliac joint as well as at least one accompanying clinical element. Recommendations for the management of r-axSpA generally include exercise and physiothera...

This study showed that allopurinol 300 mg/day has a poor efficacy and tolerability profile when used to attain a biochemical predefined target level of sUr < or =0.30 mmol/l, following 2 months of treatment. In stage 2, benzbromarone 200 mg/day was more effective and better tolerated than probenecid 2 g/day.

Objective.Acute anterior uveitis (AAU) is common in ankylosing spondylitis (AS). Golimumab (GOL), a tumor necrosis factor-α inhibitor (TNFi), has proven to be effective in the treatment of AS. To date, the effect of GOL on the incidence of AAU in AS is unknown. The objective was to study the AAU occurrence rate in patients with AS during GOL treatment and secondarily, the efficacy of GOL in daily clinical practice.Methods.The study was a multicenter prospective study in a real-world setting in patients with AS who were treated with GOL for 12 months. The occurrence of AAU was assessed in the year before the initial TNFi treatment and during GOL treatment and calculated for the period at risk for a new AAU. Measures for disease activity [Ankylosing Spondylitis Disease Activity Score (ASDAS)] and treatment response [Assessment of Spondyloarthritis international Society (ASAS20 score)] were collected.Results.In total, 93 patients (65% male, 55% TNFi-naive, 27% history of AAU) were included, with a median disease duration of 7 years and ASDAS score of 3.1. During GOL treatment, the AAU occurrence rate was reduced from 11.1 to 2.2 per 100 patient-years (rate-ratio 0.20, 95% CI 0.04–0.91). After 3 months of treatment, 41% of the patients experienced a clinically important improvement of the ASDAS score (p < 0.001) and 36% an ASDAS20 response (p < 0.001). At month 12, 49% had achieved an ASAS20 response (p < 0.001).Conclusion.In AS, the AAU occurrence rate and disease activity decreased significantly during GOL treatment. Therefore, GOL can be considered a good choice in patients with AS who need a TNFi, especially in cases of recurrent AAU. (EudraCT number: 2012-002458-21)

Objective. To compare the clinical efficacy and safety of radiation synovectomy (RSO) with intraarticular (IA) yttrium-90 plus glucocorticoids (GCs) with the efficacy and safety of IA placebo yttrium plus GCs and to identify parameters that predict efficacy.Methods. The knees of 97 patients with persistent arthritis despite outpatient treatment with IA GCs (n ‫؍‬ 113 knees), were treated with either IA 90 Y plus GCs (50%) or IA placebo yttrium plus GCs (50%), followed by 3 days of bed rest in the hospital clinic, with splinting of the treated knee. Predominant diagnoses were undifferentiated arthritis (39%) and rheumatoid arthritis (32%). The clinical effect of therapy was assessed at 6 months using a composite change index (CCI; range 0-12). The primary outcome measure was the response rate (i.e., the percentage of joints with a CCI >6). Knees with persistent arthritis after 6 months underwent crossover therapy (51% of the 90 Y plus GCs group versus 45% of the placebo plus GCs group). Adverse effects and radiologic damage during followup were documented.Results. Neither the response rate (48% in both groups), the mean CCI, nor the duration of remission was significantly different between groups. No clinically relevant short-term adverse effects were observed, except for progression of radiologic damage in 34% of the 90 Y plus GCs group versus 28% of the placebo plus GCs group (knee prosthesis placement in 8% versus 1%). The functional and radiologic status at study entry predicted the clinical effect.Conclusion. Treatment with 90 Y plus GCs with bed rest and splinting is not superior to IA GCs with bed rest and splinting. Over the short term, both treatments appeared to be safe, although a negative effect of 90 Y on cartilage and bone cannot be ruled out. Thus, it appears that RSO with 90 Y should no longer be considered the treatment of first choice for persistent arthritis of the knee.In patients with persistent synovitis despite treatment with nonsteroidal antiinflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), and/or intraarticular (IA) glucocorticoids (GCs), radiation synovectomy (or, radiosynoviorthesis [RSO]) may be indicated. RSO is performed by IA administration of a radioactive isotope; yttrium-90 is

Objectives U-Act-Early was a 2-year, randomized placebo controlled, double-blind trial, in which DMARD-naïve early RA patients were treated to the target of sustained remission (SR). Two strategies initiating tocilizumab (TCZ), with and without methotrexate (MTX), were more effective than a strategy initiating MTX. The aim of the current study was to determine longer-term effectiveness in daily clinical practice. Methods At the end of U-Act-Early, patients were included in a 3-year post-trial follow-up (PTFU), in which treatment was according to standard care and data were collected every 3 months during the first year and every 6 months thereafter. Primary end point was disease activity score assessing 28 joints (DAS28) over time. Mixed effects models were used to compare effectiveness between initial strategy groups, correcting for relevant confounders. Between the groups as randomized, proportions of patients were tested for DMARD use, SR and radiographic progression of joint damage. Results Of patients starting U-Act-Early, 226/317 (71%) participated in the PTFU. Over the total 5 years, mean DAS28 was similar between groups (P &gt; 0.20). During U-Act-Early, biologic DMARD use decreased in both TCZ initiation groups and increased in the MTX initiation group, but during follow-up this trend did not continue. SR was achieved at least once in 99% of patients. Of the 226 patients, only 30% had any radiographic progression over 5 years, without significant differences between the groups. Conclusion Although in the short-term the strategies initiating TCZ yielded the most clinical benefit, in the longer-term differences in important clinical outcomes between the strategies disappeared, probably due to continuation of the treat-to-target principle.