Effect of Health Care Providers' Focused Discussion and Proactive Education About Relapse Management on Patient Reporting of Multiple Sclerosis Relapse.

BACKGROUND: Treatments for multiple sclerosis (MS) relapse include intravenous corticosteroids and repository corticotropin injection. Despite available treatment, in the Multiple Sclerosis in America 2017 survey, only 47% of patients reported always/often contacting their MS health care provider (HCP) during relapse. In this study, the Multiple Sclerosis in America 2017 survey participants who received intravenous corticosteroids or repository corticotropin injection for treatment of past relapses completed a follow-up survey to understand how patients characterize relapse severity and to explore predictors of patients contacting their HCP during a relapse. METHODS: Patients were 18 years and older, diagnosed as having MS by an HCP, and currently using disease-modifying therapy. Patients completed an online survey assessing relapse characteristics and interactions with the HCP treating the patient's MS. Regression analysis identified predictors of patients contacting their HCP during relapse. RESULTS: Mean age of the 126 respondents was 49.2 years, 81.0% were female, and most (80.2%) had one or more relapses in the past 2 years. Patients estimated that 38.3% of their relapses were mild; 45.1%, moderate; and 16.6%, severe. Number and frequency of symptoms increased with relapse severity. Less than half (46.0%) reported they were extremely likely to contact their HCP during a relapse. The best predictors of being likely to contact the HCP during relapse were the HCP having previously discussed the importance of immediately communicating a relapse and patients' willingness to accept the HCP's recommendation for relapse treatment. CONCLUSIONS: Findings highlight the importance of HCPs' advance discussions with patients with MS regarding relapse management to increase the likelihood patients will contact their HCP during relapse.

Efficacy and tolerability of pegloticase for the treatment of chronic gout in patients refractory to conventional treatment: two randomized controlled trials.

CONTEXT: Patients with chronic disabling gout refractory to conventional urate-lowering therapy need timely treatment to control disease manifestations related to tissue urate crystal deposition. Pegloticase, monomethoxypoly(ethylene glycol)-conjugated mammalian recombinant uricase, was developed to fulfill this need. OBJECTIVE: To assess the efficacy and tolerability of pegloticase in managing refractory chronic gout. DESIGN, SETTING, AND PATIENTS: Two replicate, randomized, double-blind, placebo-controlled trials (C0405 and C0406) were conducted between June 2006 and October 2007 at 56 rheumatology practices in the United States, Canada, and Mexico in patients with severe gout, allopurinol intolerance or refractoriness, and serum uric acid concentration of 8.0 mg/dL or greater. A total of 225 patients participated: 109 in trial C0405 and 116 in trial C0406. INTERVENTION: Twelve biweekly intravenous infusions containing either pegloticase 8 mg at each infusion (biweekly treatment group), pegloticase alternating with placebo at successive infusions (monthly treatment group), or placebo (placebo group). MAIN OUTCOME MEASURE: Primary end point was plasma uric acid levels of less than 6.0 mg/dL in months 3 and 6. RESULTS: In trial C0405 the primary end point was reached in 20 of 43 patients in the biweekly group (47%; 95% CI, 31%-62%), 8 of 41 patients in the monthly group (20%; 95% CI, 9%-35%), and in 0 patients treated with placebo (0/20; 95% CI, 0%-17%; P < .001 and <.04 for comparisons between biweekly and monthly groups vs placebo, respectively). Among patients treated with pegloticase in trial C0406, 16 of 42 in the biweekly group (38%; 95% CI, 24%-54%) and 21 of 43 in the monthly group (49%; 95% CI, 33%-65%) achieved the primary end point; no placebo-treated patients reached the primary end point (0/23; 95% CI, 0%-15%; P = .001 and < .001, respectively). When data in the 2 trials were pooled, the primary end point was achieved in 36 of 85 patients in the biweekly group (42%; 95% CI, 32%-54%), 29 of 84 patients in the monthly group (35%; 95% CI, 24%-46%), and 0 of 43 patients in the placebo group (0%; 95% CI, 0%-8%; P < .001 for each comparison). Seven deaths (4 in patients receiving pegloticase and 3 in the placebo group) occurred between randomization and closure of the study database (February 15, 2008). CONCLUSION: Among patients with chronic gout, elevated serum uric acid level, and allopurinol intolerance or refractoriness, the use of pegloticase 8 mg either every 2 weeks or every 4 weeks for 6 months resulted in lower uric acid levels compared with placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00325195.

Progress in measurement instruments for acute and chronic gout studies.

Consensus exercises have identified and prioritized domains of measurement for studies in acute and chronic gout. In parallel, the technical properties of instruments for measurement in many of these domains have been assessed, with the main objective to consider the instruments in the context of the OMERACT filter of truth, discrimination, and feasibility. These data were presented and discussed at OMERACT 9 in the gout workshop, in breakout groups, and at informal meetings of the gout group. In acute gout, instruments for domains of pain, joint swelling, joint tenderness, and patient and physician global assessment have been assessed. In chronic gout, some validation exercises have been performed in instruments for domains serum urate, tophus measurement, health-related quality of life (HRQOL). In voting at OMERACT 9, the Medical Outcomes Study Short-Form 36 was endorsed as a valid instrument for measurement of HRQOL. Methods of tophus measurement were considered to have met some criteria of the OMERACT filter, but these require further work, particularly regarding sensitivity to change over shorter time periods. Priorities for future research include measurement of joint inflammation in acute gout and disability in acute and chronic gout.

Outcome domains for studies of acute and chronic gout.

Discussion and voting at OMERACT 9 confirmed 5 essential domains for outcomes of acute gout: pain, joint swelling, joint tenderness, patient global assessment and activity limitations. For studies in chronic gout 7 essential domains are: serum urate, acute gout attacks, tophus burden, health-related quality of life, activity limitations, pain, and patient global assessment. Implications of patient perspectives, discretionary domains for specific studies, measurement instruments and a possible responder index are under study.

Quality of life and disability in patients with treatment-failure gout.

OBJECTIVE: The relationship between self-reported quality of life and disability and disease severity was evaluated in subjects with treatment-failure gout (n = 110) in a prospective, 52-week, observational study. METHODS: Subjects had symptomatic crystal-proven gout of at least 2 years' duration and intolerance or refractoriness to conventional urate-lowering therapy. Serum uric acid (sUA) concentration, swollen and tender joint counts, frequency and severity of gout flares, tophus assessments, comorbidities, and patient-reported outcomes data [Medical Outcomes Study Short Form-36 (SF-36), Health Assessment Questionnaire-Damage Index] were collected. Analyses included correlations of patient-reported outcomes with clinical variables and changes in clinical status. RESULTS: Mean age of study subjects was 59 years. Mean scores on SF-36 physical functioning subscales were 34.2-46.8, analogous to persons aged >or= 75 years in the general population. Subjects with more severe gout at baseline had worse health-related quality of life (HRQOL) in all areas (p < 0.02 for all measures), compared to patients with mild-moderate disease. Number of flares reported in past year, number of tender joints, swollen joints, and tophi correlated significantly with some or all HRQOL and disability measures. sUA was not significantly correlated with any HRQOL or disability measure. Subjects with comorbidities experienced worse physical, but not mental, functioning. CONCLUSION: Severe gout is associated with poor HRQOL and disability, especially for patients who experience more gout flares and have a greater number of involved joints. Subject perceptions of gout-related functioning and pain severity appear to be highly sensitive indicators of HRQOL and disability.

Reduction of plasma urate levels following treatment with multiple doses of pegloticase (polyethylene glycol-conjugated uricase) in patients with treatment-failure gout: results of a phase II randomized study.

OBJECTIVE: To assess the efficacy of pegloticase in achieving and maintaining plasma urate levels of <6 mg/dl in gout patients in whom other treatments have failed, and to assess the pharmacokinetics and safety of pegloticase. METHODS: Forty-one patients were randomized to undergo 12-14 weeks of treatment with pegloticase at 1 of 4 dosage levels: 4 mg every 2 weeks, 8 mg every 2 weeks, 8 mg every 4 weeks, or 12 mg every 4 weeks. Plasma uricase activity, plasma urate, and antipegloticase antibodies were measured, pharmacokinetic parameters were assessed, and adverse events were recorded. RESULTS: The mean plasma urate level was reduced to

Population pharmacokinetic and pharmacodynamic analysis of pegloticase in subjects with hyperuricemia and treatment-failure gout.

Pegloticase is designed to convert urate into the easily excretable allantoin to treat hyperuricemia in gout. The aim of this analysis was to describe the pharmacokinetics and pharmacodynamics of pegloticase in 40 gout patients. Pegloticase was administered as intravenous infusions every 2 weeks at 4- and 8-mg doses or every 4 weeks at 8- or 12-mg doses for 12 weeks. Serum pegloticase concentrations, plasma urate, and serum antibody response were determined. Population pharmacokinetics and pharmacodynamics analyses were performed. Data were modeled simultaneously, and covariates were investigated (age, gender, race, body weight, ideal body weight, and antibody response). The dosing regimens to maintain uric acid levels below the therapeutic target of 6 mg/dL were then predicted by the model. The pharmacokinetics were best described by a 1-compartment linear model, while the pharmacodynamics model was fitted as a direct effect of pegloticase on uric acid concentrations with a suppressive maximum effect attributed to drug (E(max)) function. Pegloticase suppressed uric acid levels up to 83%. Weight only affected clearance and volume of distribution. No covariates affected pharmacodynamics. Simulation suggests pegloticase administered at 8 mg every 2 or 4 weeks as 2-hour intravenous infusions will maintain uric acid levels well under 6 mg/dL.