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Introduction Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). To provide additional clinical evidence in regulatory submissions for a modified-release (MR) once-daily (QD) tofacitinib formulation, we compared real-world adherence and effectiveness between patients initiating the MR QD formulation and patients initiating an immediate-release (IR) twice-daily (BID) formulation. Methods Two noninterventional cohort studies were conducted. First, adherence and two effectiveness proxies were compared between patients with RA who newly initiated tofacitinib MR 11 mg QD or IR 5 mg BID in the IBM® MarketScan® Commercial and Medicare Supplemental US insurance claims databases (March 2016–October 2018). Second, using data collected in the Corrona US RA Registry (February 2016–August 2019), two Clinical Disease Activity Index (CDAI)-based measures of effectiveness were compared between tofacitinib MR 11 mg QD and IR 5 mg BID, and against noninferiority criteria derived from placebo-controlled clinical trials of the tofacitinib IR formulation. Multiple sensitivity analyses of the registry data were conducted to reassure regulators of consistent results across different assumptions. Results In each study, approximately two-thirds of patients initiated the MR formulation. In the claims database study, improved adherence and at least comparable effectiveness were observed with tofacitinib MR vs IR over 12 months, particularly in patients without prior advanced therapy. In the registry study, the noninferiority of tofacitinib MR vs IR was demonstrated for both CDAI outcomes at ~6 months; this finding was robust across multiple sensitivity analyses. Conclusion These results demonstrate the value of real-world evidence from complementary data sources in understanding the impact of medication adherence with a QD formulation in clinical practice. These analyses were suitable for regulatory consideration as an important component of evidence for the comparability of tofacitinib MR 11 mg QD vs IR 5 mg BID in patients with RA. Trial Registration Claims database study: ClinicalTrials.gov identifier NCT04018001, retrospectively registered July 12, 2019. Corrona US RA Registry study: ClinicalTrials.gov identifier NCT04267380, retrospectively registered February 12, 2020. Electronic supplementary material The online version of this article (10.1007/s12325-020-01501-z) contains supplementary material, which is available to authorized users.

Introduction No published studies exist comparing the effectiveness of tofacitinib with other advanced therapies for the treatment of rheumatoid arthritis (RA) in real-world clinical practice. Here, we report differences in effectiveness of tofacitinib compared with standard of care, tumor necrosis factor inhibitors (TNFi), with or without concomitant methotrexate (MTX), using US Corrona registry data. Methods This observational cohort study included RA patients receiving tofacitinib (from 6 November 2012; N = 558) or TNFi (from 1 November 2001; N = 8014) with or without MTX until 31 July 2016. Efficacy outcomes at 6 months included modified American College of Rheumatology 20% responses, Clinical Disease Activity Index (CDAI) and Pain. Outcomes were compared between patients receiving TNFi and tofacitinib with or without MTX and by line of therapy. Outcomes within therapy lines were compared using propensity-score matching; between-group differences were estimated using mixed-effects regression models. Results Patients receiving tofacitinib had longer RA duration and a greater proportion had previously received biologics than those receiving TNFi; other baseline characteristics were comparable. In patients receiving second- and third-line TNFi therapy, CDAI low disease activity/remission response rates were significantly better with concomitant MTX. Too few patients received tofacitinib as second line for meaningful assessment. No significant differences were observed in outcomes between tofacitinib as monotherapy and tofacitinib with concomitant MTX. Conclusions In clinical practice, TNFi efficacy is improved with concomitant MTX in the second and third line. In the third/fourth line, patients are likely to achieve similar efficacy with tofacitinib monotherapy, or TNFi or tofacitinib in combination with MTX. Funding Pfizer Inc Electronic supplementary material The online version of this article (10.1007/s40744-019-00177-4) contains supplementary material, which is available to authorized users.

Dose escalation of infliximab in both primary and secondary nonresponders is widely reported; however, the usefulness of dose escalation has been disputed. The objective of this analysis is to evaluate trends in clinical efficacy following multiple infliximab dose escalations in patients with rheumatoid arthritis (RA). Patients enrolled in a US RA registry were included if they initiated infliximab at 3 mg/kg every 8 weeks, received ≥ 1 infliximab dose escalation within 12 months of initiation, and had ≥ 1 visit following dose escalation. Trends in mean Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire (HAQ) scores from visits following dose escalations were evaluated. In patients who received 2 or 3 dose escalations, the initial (1 or 2) dose escalations resulted in reduced mean CDAI scores, but subsequent escalations did not further reduce disease activity. In patients who received ≥ 4 dose escalations, mean CDAI scores did not further reduce disease activity over time. Mean HAQ scores were stable over time in patients who received 2 or 3 dose escalations. In patients who received ≥ 4 dose escalations, mean HAQ scores decreased following 1 dose escalation but progressively increased following subsequent dose escalations. Initial dose escalations (from 3 mg/kg to the equivalent of approximately 5 to 7 mg/kg) may be useful in controlling disease activity; however, there may be diminishing clinical benefit of further escalations, which can also increase the potential risk for infection and increase incremental drug costs. • Initial infliximab dose escalations (1 to 2) may be useful in lowering disease activity in patients with rheumatoid arthritis. • There does not appear to be a clinical benefit in infliximab dose escalations above the equivalent of 5 to 7 mg/kg.

Objective Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). We compared 5-year adverse event (AE) incidence rates (IRs) between patients initiating tofacitinib and those initiating new biological disease-modifying antirheumatic drugs (bDMARDs) within the United States (US) Corrona RA registry. Methods IRs (number of first events/100 patient-years) of major adverse cardiovascular events (MACE), serious infection events (SIEs), herpes zoster (HZ), malignancies, and death were estimated among tofacitinib and bDMARD initiators, regardless of dose/schedule, between November 6, 2012 (US Food and Drug Administration tofacitinib approval), and July 31, 2018 (follow-up through January 31, 2019). Propensity score (PS) methods were used to control for nonrandom prescribing practices. Hazard ratios (HRs) were calculated to compare rates using multivariable-adjusted Cox regression. Different risk windows were used for acute (MACE, SIEs, HZ, and venous thromboembolic events [VTEs]) and long-term (malignancy and death) events. VTEs were assessed descriptively. Results For MACE, SIEs, and HZ, 1999 (3152.1 patient-years) and 8358 (12 869.4 years) tofacitinib and bDMARD initiators were included, respectively; for malignancy/death, 1999 (4505.6 patient-years) and 6354 (16 670.8 patient-years) initiators were included, respectively. AE rates were similar across cohorts, except for HZ, which was significantly higher with tofacitinib versus bDMARDs (PS-trimmed adjusted HR 2.32; 95% confidence interval [CI] 1.43-3.75). There were 45 (zero serious) and 88 (five serious) HZ events with tofacitinib and bDMARDs, respectively. Sensitivity analyses demonstrated similar results. VTE IRs (95% CI) were 0.29 (0.13-0.54) and 0.33 (0.24-0.45) for tofacitinib and bDMARDs, respectively. Conclusion In this registry analysis, both cohorts had similar MACE, SIE, malignancy, death, and VTE rates; HZ rates were higher for tofacitinib initaitors than for bDMARD initiators.

Background: Tofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). Real-world data (RWD) complement clinical trial data in assessing long-term safety. To our knowledge, this is the first long-term comparative RWD analysis of tofacitinib. Objectives: To compare 5-year adverse event (AE) incidence rates (IRs) in patients (pts) starting tofacitinib vs biological (b)DMARDs using cohorts from the US Corrona RA registry. Methods: This prospective, observational 5-year study embedded in the ongoing US Corrona RA registry routinely collected 9 categories of predefined AEs from participating physicians. Real-world safety event rates of major adverse cardiovascular events (MACE), serious infectious events (SIEs) and herpes zoster (HZ; serious and non-serious) were compared in pts with RA who started tofacitinib or a bDMARD regardless of dose/schedule between 6 Nov 2012 (US FDA approval) and 30 Jun 2017 (follow-up through 31 Dec 2017). Endpoints were selected a priori as having sufficient power to detect a 2-fold difference between cohorts at this datacut; there was insufficient power to assess malignancy. Baseline variables with a standardised difference >│0.10│ between tofacitinib and bDMARD initiators, and a priori selected covariates (gender, age, line of therapy, history of AE of interest) were used to construct propensity scores (PS) to derive a PS-trimmed (primary) population and a PS–matched population for sensitivity analysis (ratio: max. 4 bDMARD:1 tofacitinib; calliper=0.05). Pts were followed from initiation until an AE of interest, discontinuation and/or start of a new therapy +90 days, death or end of follow-up, whichever came first. Crude IRs (events/100 pt–years [PY]) were estimated; multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) comparing rates of first events between cohorts. Results: In total, 1544 tofacitinib (2138.2 PY) and 7083 bDMARD (9904.9 PY) initiators were included. PS–trimming resulted in 1117 tofacitinib and 5542 bDMARD initiators. Rates of MACE and SIEs were similar in both cohorts (Fig 1A); adjusted HRs (95% confidence intervals [CIs]) were: MACE 0.60 (0.30, 1.18); SIEs 0.99 (0.72, 1.36; Fig 1B). HZ IR was higher for tofacitinib vs bDMARDs (Fig 1A); HRs for HZ were significantly increased with tofacitinib vs bDMARDs (adjusted HR 2.12 [1.22, 3.66]; Fig 1B); all HZ events were non-serious with tofacitinib. Similar results were observed in PS-matched populations. Conclusion: This is the first comparative analysis of RWD for tofacitinib and bDMARDs to use PS-trimmed and PS-matched analyses to adjust for channelling/prescribing patterns for newly approved therapies. Pts starting tofacitinib or bDMARDs for RA had similar rates of MACE and SIEs. Tofacitinib initiators had higher HZ IRs vs bDMARD initiators. These results are consistent with long-term clinical trial findings. Acknowledgement: Sponsors: Corrona, LLC. Corrona is supported by contracted subscriptions with multiple companies. This was a Corrona/Pfizer collaboration with Pfizer financial support. Medical writing support provided by Anthony G McCluskey of CMC Connect and funded by Pfizer Inc. Disclosure of Interests: Joel Kremer Grant/research support from: AbbVie, Genentech, Lilly, Novartis, Pfizer, Consultant for: AbbVie, Amgen, BMS, Genentech, Lilly, Regeneron, Sanofi, Pfizer, Clifton Bingham Grant/research support from: BMS, Consultant for: AbbVie, BMS, Eli Lilly, Genentech/Roche, Janssen, Pfizer, Sanofi/Regeneron, Laura Cappelli Grant/research support from: Bristol-Myers Squibb, Consultant for: Regeneron/Sanofi Genzyme, Carol Etzel Shareholder of: Corrona, LLC, Consultant for: Merck, Employee of: Corrona, LLC, Jeffrey Greenberg Shareholder of: Corrona, LLC, Consultant for: Eli Lilly, Genentech, Janssen, Novartis, and Pfizer Inc, Employee of: Corrona, LLC, Jamie Geier Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ann Madsen Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Connie Chen Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Alina Onofrei Employee of: Corrona, LLC, Christine Barr Shareholder of: Corrona, LLC, Employee of: Corrona, LLC, Dimitrios A Pappas Grant/research support from: AbbVie, Consultant for: AbbVie, Employee of: Corrona, Heather J. Litman: None declared, Kimberly J Dandreo Employee of: Corrona, LLC, Andrea Shapiro Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Carol A. Connell Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Arthur Kavanaugh Grant/research support from: UCB Pharma

Background Registry studies provide a valuable source of comparative safety data for tumor necrosis factor inhibitors (TNFi) used in rheumatoid arthritis (RA), but they are subject to channeling bias. Comparing safety outcomes without accounting for channeling bias can lead to inaccurate comparisons between TNFi prescribed at different stages of the disease. In the present study, we examined the incidence of serious infection and other adverse events during certolizumab pegol (CZP) use vs other TNFi in a U.S. RA cohort before and after using a methodological approach to minimize channeling bias. Methods Patients with RA enrolled in the Corrona registry, aged ≥ 18 years, initiating CZP or other TNFi (etanercept, adalimumab, golimumab, or infliximab) after May 1, 2009 (n = 6215 initiations), were followed for ≤ 12 months. A propensity score (PS) model was used to control for baseline characteristics associated with the probability of receiving CZP vs other TNFi. Incidence rate ratios (IRRs) of serious infectious events (SIEs), malignancies, and cardiovascular events (CVEs) in the CZP group vs other TNFi group were calculated with 95% CIs, before and after PS matching. Results Patients were more likely to initiate CZP later in the course of therapy than those initiating other TNFi. CZP initiators (n = 975) were older and had longer disease duration, more active disease, and greater disability than other TNFi initiators (n = 5240). After PS matching, there were no clinically important differences between CZP (n = 952) and other TNFi (n = 952). Before PS matching, CZP was associated with a greater incidence of SIEs (IRR 1.53 [95% CI 1.13, 2.05]). The risk of SIEs was not different between groups after PS matching (IRR 1.26 [95% CI 0.84, 1.90]). The 95% CI of the IRRs for malignancies or CVEs included unity, regardless of PS matching, suggesting no difference in risk between CZP and other TNFi. Conclusions After using PS matching to minimize channeling bias and compare patients with a similar likelihood of receiving CZP or other TNFi, the 1-year risk of SIEs, malignancies, and CVEs was not distinguishable between the two groups. Electronic supplementary material The online version of this article (doi:10.1186/s13075-017-1496-5) contains supplementary material, which is available to authorized users.

Midurethral slings are increasingly used for the treatment of stress incontinence, but there are limited data comparing types of slings and associated complications.We performed a multicenter, randomized equivalence trial comparing outcomes with retropubic and transobturator midurethral slings in women with stress incontinence. The primary outcome was treatment success at 12 months according to both objective criteria (a negative stress test, a negative pad test, and no retreatment) and subjective criteria (self-reported absence of symptoms, no leakage episodes recorded, and no retreatment). The predetermined equivalence margin was +/-12 percentage points.A total of 597 women were randomly assigned to a study group; 565 (94.6%) completed the 12-month assessment. The rates of objectively assessed treatment success were 80.8% in the retropubic-sling group and 77.7% in the transobturator-sling group (3.0 percentage-point difference; 95% confidence interval [CI], -3.6 to 9.6). The rates of subjectively assessed success were 62.2% and 55.8%, respectively (6.4 percentage-point difference; 95% CI, -1.6 to 14.3). The rates of voiding dysfunction requiring surgery were 2.7% in those who received retropubic slings and 0% in those who received transobturator slings (P=0.004), and the respective rates of neurologic symptoms were 4.0% and 9.4% (P=0.01). There were no significant differences between groups in postoperative urge incontinence, satisfaction with the results of the procedure, or quality of life.The 12-month rates of objectively assessed success of treatment for stress incontinence with the retropubic and transobturator approaches met the prespecified criteria for equivalence; the rates of subjectively assessed success were similar between groups but did not meet the criteria for equivalence. Differences in the complications associated with the two procedures should be discussed with patients who are considering surgical treatment for incontinence. (ClinicalTrials.gov number, NCT00325039.)

NIH/NIDDK, Bethesda, MarylandAims: To describe perineal surface patch electromyography (EMG) activity during urodynamics (UDS) and compareactivity between filling and voiding phases and to assess for a relationship between preoperative EMG activity andpostoperative voiding symptoms. Methods: 655 women underwent standardized preoperative UDS that included peri-neal surface EMG prior to undergoing surgery for stress urinary incontinence. Pressure-flow studies were evaluatedfor abdominal straining and interrupted flow. Quantitative EMG values were extracted from 10 predetermined time-points and compared between fill and void. Qualitative EMG activity was assessed for the percent of time EMG wasactive during fill and void and for the average amplitude of EMG during fill compared to void. Postoperative voidingdysfunction was defined as surgical revision or catheterization more than 6 weeks after surgery. Fisher’s exact testwith a 5% two-sided significance level was used to assess differences in EMG activity and postoperative voiding dys-function. Results: 321 UDS had interpretable EMG studies, of which 131 (41%) had EMG values at all 10 predeter-mined and annotated time-points. Quantitative and qualitative EMG signals during flow were usually greater thanduring fill. The prevalence of postoperative voiding dysfunction in subjects with higher preoperative EMG activityduring void was not significantly different. Results were similar in the 42 subjects who had neither abdominal strain-ing during void nor interrupted flow. Conclusions: Perineal surface patch EMG did not measure expected pelvic floorand urethral sphincter relaxation during voiding. Preoperative EMG did not predict patients at risk for postoperativevoiding dysfunction. Neurourol. Urodynam. 2011 Wiley-Liss, Inc.Key words: electromyography; pelvic floor; stress urinary incontinence; urethra; urodynamics; voiding dysfunction

To identify clinical and demographic factors predictive of midurethral sling failure.Overall treatment failure was defined by one or more of the following objective outcomes: a positive stress test, positive 24-hour pad test or retreatment for stress urinary incontinence (SUI); subjective outcomes: self reported SUI by the Medical, Epidemiologic and Social Aspect of Aging questionnaire, incontinent episodes by 3-day diary, or retreatment for SUI, or a combination of these. Logistic regression models adjusting for sling type and clinical site were used to predict odds of overall treatment failure after univariable analysis. Models were also fit to compare factors associated with objective failure and subjective failure only.Previous UI surgery (odds ratio [OR] 1.99, 95% confidence interval [CI] 1.14-3.47); maximum Q-tip excursion30° (OR 1.89, 95% CI 1.16-3.05); Medical, Epidemiologic and Social Aspect of Aging questionnaire urge score per 10 points (OR 1.97, 95% CI 1.21-3.21); and pad weight per 10 g (OR 1.06, 95% CI 1.02-1.10) were predictors of overall failure. Having concomitant surgery (OR 0.44, 95% CI 0.22-0.90) was predictive of subjective failure only rather than objective failure. Age per 10 years (OR 1.48, 95% CI 1.14-1.90); Urogenital Distress Inventory score per 10 points (OR 1.09, 95% CI 1.02-1.17); pad weight per 10 g (OR 1.05, 95% CI 1.01-1.10) were predictive of objective failure compared with subjective failure only. Associations of risk factors and failure were similar independent of sling type (retropubic or transobturator).Twelve months after surgery, risk factors for overall and objective treatment failure were similar in women undergoing retropubic and transobturator sling procedures. This information may assist in counseling patients regarding efficacy of sling procedures and in setting expectations for women at increased odds for treatment failure.ClinicalTrials.gov, www.clinicaltrials.gov, NCT00325039.II.

We compared urinary incontinence severity measures and the impact of stress urinary incontinence in normal, overweight and obese women.Baseline characteristics of subjects in the SISTEr (655) and the TOMUS (597) were analyzed. Body mass index was defined as normal (less than 25 kg/m(2)), overweight (25 to less than 30 kg/m(2)) and obese (30 kg/m(2) or greater). Independent urinary incontinence severity measures included a 3-day diary including incontinence episode frequency, Urogenital Distress Inventory scores and Valsalva leak point pressure from urodynamic testing. Impact was measured using the Incontinence Impact Questionnaire. Multivariable regression models were fit for each severity measure (Urogenital Distress Inventory, incontinence episode frequency, Valsalva leak point pressure and Incontinence Impact Questionnaire) on weight category. Covariates included age, race, diabetes and variables significantly associated with body mass index on bivariate analysis.Mean age (SD) of participants was 51.9 (10.3) in SISTEr and 52.9 (11.0) in TOMUS. In each trial 45% of subjects were obese. In SISTEr multivariable regression analyses showed that higher weight category was independently associated with higher mean Urogenital Distress Inventory score (p = 0.003), incontinence episode frequency (p0.0001), Valsalva leak point pressure (p = 0.003) and Incontinence Impact Questionnaire score (p = 0.0004). In TOMUS higher weight category was not associated with Urogenital Distress Inventory score (p = 0.24) but was associated with higher incontinence episode frequency (p = 0.0003), Valsalva leak point pressure (p = 0.0006) and Incontinence Impact Questionnaire score (p0.0001).Obese women undergoing surgery for stress urinary incontinence report more incontinence episodes, more symptom distress and worse quality of life despite better measure of urethral function (higher Valsalva leak point pressure) on urodynamics.

Background and purpose Urodynamic studies (UDS) are routinely obtained prior to surgery for stress urinary incontinence (SUI) despite a lack of evidence that UDS information has an actual impact on outcome. The primary aim of this non-inferiority randomized clinical trial is to determine whether women with symptomatic, uncomplicated SUI who undergo only a basic office evaluation (BOE) prior to SUI surgery (No UDS arm) have non-inferior treatment outcomes compared to women who have BOE and UDS (UDS arm). Secondary aims are: 1) to determine how often physicians use preoperative UDS results to alter clinical and surgical decision-making, 2)to compare the amount of improvement in incontinence outcomes, and 3) to determine the incremental cost and utility of performing UDS compared with not performing UDS. Methods After an initial basic office evaluation, women planning surgery for uncomplicated SUI who consent to study participation will be randomized to receive preoperative UDS or No UDS. Treatment will be planned and performed by the surgeon utilizing all the data available to them. We will compare results from the basic office evaluation (No UDS) with results from the basic office evaluation and preoperative UDS. Results The primary outcome will be measured at 12 months using responses to the Urogenital Distress Inventory and the Patient Global Index-Improvement. Conclusions Randomized trials comparing the effects of different diagnostic alternatives on treatment outcomes pose study design challenges. A non-inferiority design is appropriate when comparing a less invasive and less expensive alternative with a standard of care approach.

Aims The Urinary Incontinence Treatment Network (UITN) was established in 2000 as a multi-disciplinary, multi-institutional network by the National Institute for Diabetes, Digestive, and Kidney Diseases (NIDDK) to investigate treatments for urinary incontinence in women.

We assessed the relationships among severity measures of urinary incontinence in women with stress predominant symptoms enrolled in a randomized clinical trial comparing 2 surgical techniques (Burch colposuspension vs pubovaginal sling) for stress urinary incontinence.A total of 655 women underwent a standardized preoperative assessment that included the Medical, Epidemiological and Social Aspects of Aging questionnaire, Urogenital Distress Inventory, Incontinence Impact Questionnaire, 3-day voiding diary, 24-hour pad test, a supine empty bladder stress test and Valsalva leak point pressure measurements. Correlations were estimated using Spearman correlation coefficients and 95% confidence intervals. T tests at alpha=0.05 were conducted to compare the distributions of the continuous severity measure between patients with positive and negative supine empty bladder stress test.Baseline mean scores on Medical, Epidemiological and Social Aspects of Aging, Urogenital Distress Inventory and Incontinence Impact Questionnaire were 25.8, 151 and 171, respectively. Mean incontinence episode frequency and pad weight were 3.2 per day and 43.5 gm, respectively. Supine empty bladder stress test was positive in 218 patients, and 428 patients had valid Valsalva leak point pressure measurements with a mean Valsalva leak point pressure of 80 cm H(2)O. Weak to moderate correlations were observed between Medical, Epidemiological and Social Aspects of Aging, incontinence episode frequency, pad weight, Incontinence Impact Questionnaire and Urogenital Distress Inventory. On the other hand, Valsalva leak point pressure correlated poorly with all variables measured. The sensitivity and specificity of the supine empty bladder stress test to predict intrinsic sphincter dysfunction were 49% and 60%, respectively.Urinary incontinence severity measures correlate moderately with each other at best. While Medical, Epidemiological and Social Aspects of Aging demonstrated stronger correlations with the other measures of severity and quality of life, Valsalva leak point pressure did not. Supine empty bladder stress test did not demonstrate a clinically significant association among severity measures.

Objective The aim of this study was to identify factors associated with urinary incontinence severity at baseline in women undergoing surgery for stress incontinence. Study design Baseline data were obtained from 650 women (age 28 to 81 years) with stress incontinence participating in a randomized surgical trial. Severity of incontinence was defined by the mean number of incontinence episodes per day recorded in a 3-day bladder diary. The relationships between severity and several baseline variables were examined, including demographics, medical, obstetric, and gynecologic history, body mass index, smoking status, Q-tip displacement, and Pelvic Organ Prolapse Quantification stage (POP-Q). Results In a multivariable model, severity of incontinence was positively associated with body mass index ( P = .0003) and current smoking ( P = .01), and negatively associated with prolapse stage ( P P = .042). Conclusion Incontinence severity in a surgical population was independently associated with 2 modifiable factors, obesity and tobacco use, as well as pelvic support.

The results of the VeGAS 2 trial further extend knowledge of the AngioJet device and demonstrate benefits in success, safety, and greater convenience to the patient and physician due to a single, combined procedure for thrombus removal and definitive intervention in this high-risk patient group. AngioJet should be regarded as the therapy of choice for treatment of thrombotic SVGs or native coronary arteries.

Background TNF inhibitors (TNFi) can be used as monotherapy (mono) or in combination (combo) with conventional DMARDS (cDMARDS). Clinical trial data and European registry data have shown evidence of better effectiveness of TNFi combo therapy than mono. Effectiveness of mono vs combo in US clinical practice, in particular among biologic naive and experienced patients, has not been assessed. Objectives This study was carried out to quantify the prevalence and effectiveness of TNFi monotherapy use in US clinical practice. A secondary objective was to contrast this with tofacitinib (tofa) monotherapy use and effectiveness. Methods RA patients initiating a TNFi (adalimumab, etanercept, infliximab, golimumab, certolizumab pegol) or tofa with a six month follow-up in Corrona US were identified. A subcohort of TNFi initiations after 11/6/2012 (market approval of tofa) were used for comparisons with tofa initiators. We defined combo therapy as TNFi or tofa used with MTX alone and mono as no use of any cDMARD. The primary outcome was achieving low disease activity (LDA) or remission based on CDAI (≤10) at 6 months. Patients switching to another biologic prior to 6 months were defined as non-responders. Secondary outcomes included modified ACR20/50/70 and mean change in CDAI. Combo and mono initiators were matched within line of therapy using a propensity score. Covariates for the model were selected if the standardized mean difference between the groups >0.1. Results There were 7076 TNFi initiations in Corrona, with 2091 (30%) mono initiations. Mono by line of therapy was 21%, 35% and 41% for 2nd, 3rd and 4th line therapy, respectively. There were 325 tofa initiations with 201 (61%) mono and mono rates of 50%, 65% and 63% for 2nd, 3rd and 4th line therapy, respectively. In the matched populations, across outcome measures (Table 1), TNFi combo was more effective than TNFi mono in 2nd line therapy (55.6% LDA vs 47.1% LDA) and similar in 3rd and 4th line therapy. Tofa combo therapy was similar to mono in the matched populations (35.4% LDA vs 32.3% LDA). Tofa mono was similar to TNFi combo therapy in the matched populations (33.3% LDA vs 33.3% LDA). Conclusions TNFi monotherapy is common in U.S. clinical practice. TNFi monotherapy is less effective than combination therapy especially in biologic naive patients. There is no evidence that tofa monotherapy is less effective than tofa combination therapy or TNFi combination therapy. Acknowledgement This study is sponsored by Corrona, LLC. The Corrona RA registry has been supported through contracted subscriptions in the last two years by AbbVie, Amgen, BMS, Crescendo, Genentech, Horizon Pharma USA, Janssen, Eli Lilly, Novartis, Pfizer, and UCB. Disclosure of Interest G. Reed Shareholder of: Corrona, LLC, Employee of: Corrona, LLC, R. Gerber Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc., Y. Shan Employee of: Corrona, LLC, L. Takiya Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc., K. Dandreo Employee of: Corrona, LLC, D. Gruben Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc., J. Kremer Shareholder of: Corrona, LLC, Consultant for: AbbVie, Amgen, BMS, Genentech, GSK, Lilly, Medimmune, Pfizer, Sanofi, Employee of: Corrona, LLC, Speakers bureau: Genentech (for non-branded talk only), G. Wallenstein Shareholder of: Pfizer, Inc., Employee of: Pfizer, Inc.

The purpose of this study was to develop and test a unique, new pelvic floor surgery complication scale and compare it with an existing validated measure.Surgeons from 2 clinical trials networks rated complications based on perceived patient bother, severity, and duration of disability to develop a pelvic floor complication scale (PFCS). PFCS scores were calculated for subjects in 2 multicenter pelvic floor surgical trials. The PFCS and modified Clavien-Dindo scores were evaluated for associations with length of hospitalization, satisfaction, and quality-of-life measures (health utilities index, short form-36, urogenital distress inventory, and incontinence impact questionnaire).We calculated PFCS scores for 977 subjects. Higher PFCS and Clavien-Dindo scores similarly were associated with longer length of hospitalization (P.01), lower satisfaction (P.01), lower Health Utilities Index scores (P = .02), lower short form-36 scores (P = .02), higher urogenital distress Inventory scores (P.01), and incontinence impact questionnaire scores (P.01) at 3 months. No associations were present at 1 year.The PFCS compares favorably to the validated modified Clavien-Dindo instrument.

Urodynamic studies are commonly performed in women before surgery for stress urinary incontinence, but there is no good evidence that they improve outcomes.We performed a multicenter, randomized, noninferiority trial involving women with uncomplicated, demonstrable stress urinary incontinence to compare outcomes after preoperative office evaluation and urodynamic tests or evaluation only. The primary outcome was treatment success at 12 months, defined as a reduction in the score on the Urogenital Distress Inventory of 70% or more and a response of "much better" or "very much better" on the Patient Global Impression of Improvement. The predetermined noninferiority margin was 11 percentage points.A total of 630 women were randomly assigned to undergo office evaluation with urodynamic tests or evaluation only (315 per group); the proportion in whom treatment was successful was 76.9% in the urodynamic-testing group versus 77.2% in the evaluation-only group (difference, -0.3 percentage points; 95% confidence interval, -7.5 to 6.9), which was consistent with noninferiority. There were no significant between-group differences in secondary measures of incontinence severity, quality of life, patient satisfaction, rates of positive provocative stress tests, voiding dysfunction, or adverse events. Women who underwent urodynamic tests were significantly less likely to receive a diagnosis of overactive bladder and more likely to receive a diagnosis of voiding-phase dysfunction, but these changes did not lead to significant between-group differences in treatment selection or outcomes.For women with uncomplicated, demonstrable stress urinary incontinence, preoperative office evaluation alone was not inferior to evaluation with urodynamic testing for outcomes at 1 year. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT00803959.).

To describe perineal surface patch electromyography (EMG) activity during urodynamics (UDS) and compare activity between filling and voiding phases and to assess for a relationship between preoperative EMG activity and postoperative voiding symptoms.655 women underwent standardized preoperative UDS that included perineal surface EMG prior to undergoing surgery for stress urinary incontinence. Pressure-flow studies were evaluated for abdominal straining and interrupted flow. Quantitative EMG values were extracted from 10 predetermined time-points and compared between fill and void. Qualitative EMG activity was assessed for the percent of time EMG was active during fill and void and for the average amplitude of EMG during fill compared to void. Postoperative voiding dysfunction was defined as surgical revision or catheterization more than 6 weeks after surgery. Fisher's exact test with a 5% two-sided significance level was used to assess differences in EMG activity and postoperative voiding dysfunction.321 UDS had interpretable EMG studies, of which 131 (41%) had EMG values at all 10 predetermined and annotated time-points. Quantitative and qualitative EMG signals during flow were usually greater than during fill. The prevalence of postoperative voiding dysfunction in subjects with higher preoperative EMG activity during void was not significantly different. Results were similar in the 42 subjects who had neither abdominal straining during void nor interrupted flow.Perineal surface patch EMG did not measure expected pelvic floor and urethral sphincter relaxation during voiding. Preoperative EMG did not predict patients at risk for postoperative voiding dysfunction.

OBJECTIVE To estimate whether perioperative and postoperative outcomes after Burch colposuspension or pubovaginal sling for stress urinary incontinence (SUI) differed with age. METHODS This study was a prospective secondary analysis of the Stress Incontinence Surgical Treatment Efficacy Trial. Baseline characteristics, adverse events, and 2-year outcomes of women at least 65 years old were compared with those younger than 65 years using chi(2) and t tests. Multivariable analyses were performed, including age and outcomes that differed between age groups on univariable analysis, adjusting for variables that differed by age group at baseline and by surgical treatment group. RESULTS Six-hundred fifty-five women were included in analyses of perioperative events and 520 for 2-year outcomes. Mean age (+/-standard deviation) was 69.7 (+/-3.7) years in the older group and 49.4 (+/-8.2) in the younger group. Older women had slightly longer time to normal activities (50 days compared with 42 days, P=.05), but there was no difference in time to normal voiding (14 days compared with 11 days, P=.42). Older women were more likely to have a positive stress test at follow-up (odds ratio [OR] 3.7, 95% confidence interval [CI] 1.70-7.97, P=.001), less subjective improvement in stress (8 point lesser decrease, 95% CI 1.5-14.1, P=.02), and urge incontinence (7 point lesser decrease, 95% CI 1.5-12.2, P=.01) by the Medical and Epidemiologic Social Aspects of Aging questionnaire, and were more likely to undergo surgical retreatment for SUI (OR 3.9, 95% CI 1.30-11.48). Perioperative adverse events and length of stay did not differ between groups. CONCLUSION Older women undergoing surgery for stress incontinence can expect to do as well as younger women with respect to perioperative outcomes, but experience 2-year outcomes that are worse.

We determined the clinicodemographic factors associated with complications of continence procedures, the impact of concomitant surgery on the complication rate and the relationship between the incidence of cystitis and the method of postoperative bladder drainage.We reviewed serious adverse events and adverse events in the Stress Incontinence Surgical Efficacy Trial, a randomized trial comparing Burch colposuspension to the autologous rectus fascial sling. Clinicodemographic variables were analyzed to determine those associated with adverse events using logistic regression analysis. Complications were stratified based on the presence or absence of concomitant surgery. Differences in complication rates (controlling for concomitant surgery) and cystitis rates (controlling for the bladder emptying method) were compared using Fisher's exact test.Blood loss (p = 0.0002) and operative time (p0.0001) were significantly associated with an adverse event. Patients who underwent concomitant surgery had a significantly higher serious adverse event rate (14.2% vs 7.3%, p = 0.01) and adverse event rate (60.5% vs 48%, p0.01) than patients who underwent continence surgery alone. Cystitis rates were higher in the sling vs the Burch group up to 6 weeks postoperatively regardless of concomitant surgery status (p0.01). Intermittent self-catheterization increased the cystitis rate by 17% and 23% in the Burch and sling groups, respectively.Concomitant surgery at continence surgery increased the risk of complications. Sling surgery was associated with a higher risk of cystitis within the first 6 weeks postoperatively. Intermittent self-catheterization increased the risk of cystitis in each group. Complications were associated with surgical factors and not with patient related factors.

Many surgical procedures are available for women with urinary stress incontinence, yet few randomized clinical trials have been conducted to provide a basis for treatment recommendations.We performed a multicenter, randomized clinical trial comparing two procedures--the pubovaginal sling, using autologous rectus fascia, and the Burch colposuspension--among women with stress incontinence. Women were eligible for the study if they had predominant symptoms associated with the condition, a positive stress test, and urethral hypermobility. The primary outcomes were success in terms of overall urinary-incontinence measures, which required a negative pad test, no urinary incontinence (as recorded in a 3-day diary), a negative cough and Valsalva stress test, no self-reported symptoms, and no retreatment for the condition, and success in terms of measures of stress incontinence specifically, which required only the latter three criteria. We also assessed postoperative urge incontinence, voiding dysfunction, and adverse events.A total of 655 women were randomly assigned to study groups: 326 to undergo the sling procedure and 329 to undergo the Burch procedure; 520 women (79%) completed the outcome assessment. At 24 months, success rates were higher for women who underwent the sling procedure than for those who underwent the Burch procedure, for both the overall category of success (47% vs. 38%, P=0.01) and the category specific to stress incontinence (66% vs. 49%, P0.001). However, more women who underwent the sling procedure had urinary tract infections, difficulty voiding, and postoperative urge incontinence.The autologous fascial sling results in a higher rate of successful treatment of stress incontinence but also greater morbidity than the Burch colposuspension. (ClinicalTrials.gov number, NCT00064662 [ClinicalTrials.gov] .).

To understand the patient burden of study procedures/measures at completion of a randomized controlled trial (RCT) requiring extensive testing and follow-up visits. A survey sent after completing the 2-year visit of an RCT comparing Burch colposuspension and fascial retropubic sling to treat stress urinary incontinence assessed degree of bother for seven study procedures, eight study-related factors, and possible motivations to participate in the study. A total of 450 study participants (88%) returned the survey. Urodynamic testing was the most bothersome procedure, followed by 24-h pad test and Q-tip test. Self-administered questionnaires were the least bothersome. Main reasons to participate in the study were to help others, obtain better knowledge about the condition, and be guided by a committed team of investigators/study coordinators. At the end of a large multicenter RCT, we learned from a confidential patient survey that the most burdensome activities involved invasive procedures, frequent visits, and multiple forms to fill out.

Objective To describe surgical complications in 597 women over a 24-month period after randomization to retropubic or transobturator midurethral slings. Study Design During the Trial of Midurethral Slings study, the Data Safety Monitoring Board regularly reviewed summary reports of all adverse events using the Dindo Surgical Complication Scale. Logistic regression models were created to explore associations between clinicodemographic factors and surgical complications. Results A total of 383 adverse events were observed among 253 of the 597 women (42%). Seventy-five adverse events (20%) were classified as serious (serious adverse events); occurring in 70 women. Intraoperative bladder perforation (15 events) occurred exclusively in the retropubic group. Neurologic adverse events were more common in the transobturator group than in retropubic (32 events vs 20 events, respectively). Twenty-three (4%) women experienced mesh complications, including delayed presentations, in both groups. Conclusion Adverse events vary by procedure, but are common after midurethral sling. Most events resolve without significant sequelae.

The aim of this study was to determine whether preoperative voiding detrusor pressures were associated with postoperative outcomes after stress incontinence surgery.Opening detrusor pressure, detrusor pressure at maximum flow (p (det) Q(max)), and closing detrusor pressure were assessed from 280 valid preoperative urodynamic studies in subjects without advanced prolapse from a multicenter randomized trial comparing Burch and autologous fascia sling procedures. These pressures were compared between subjects with and without overall success, stress-specific success, postoperative detrusor overactivity, and postoperative urge incontinence using independent sample t tests.There were no clinically or statistically significant differences in mean preoperative voiding detrusor pressures in any comparison of postoperative outcomes.We found no evidence that preoperative voiding detrusor pressures predict outcomes in women with stress predominant urinary incontinence undergoing Burch or autologous fascial sling procedures.

Background: Women with urge urinary incontinence are commonly treated with antimuscarinic medications, but many discontinue therapy. Objective: To determine whether combining antimuscarinic drug therapy with supervised behavioral training, compared with drug therapy alone, improves the ability of women with urge incontinence to achieve clinically important reductions in incontinence episodes and to sustain these improvements after discontinuing drug therapy. Design: 2-stage, multicenter, randomized clinical trial conducted from July 2004 to January 2006. Setting: 9 university-affiliated outpatient clinics. Patients: 307 women with urge-predominant incontinence. Intervention: 10 weeks of open-label, extended-release tolterodine alone (n = 153) or combined with behavioral training (n = 154), followed by discontinuation of therapy and follow-up at 8 months. Measurements: The primary outcome, measured at 8 months, was no receipt of drugs or other therapy for urge incontinence and a 70% or greater reduction in frequency of incontinence episodes. Secondary outcomes were reduction in incontinence, self-reported satisfaction and improvement, and scores on validated questionnaires measuring symptom distress and bother and health-related quality of life. Study staff who performed outcome evaluations, but not participants and interventionists, were blinded to group assignment. Results: 237 participants completed the trial. According to life-table estimates, the rate of successful discontinuation of therapy at 8 months was the same in the combination therapy and drug therapy alone groups (41% in both groups; difference, 0 percentage points [95% Cl, -12 to 12 percentage points]). A higher proportion of participants who received combination therapy than drug therapy alone achieved a 70% or greater reduction in incontinence at 10 weeks (69% vs. 58%; difference, 11 percentage points [Cl, -0.3 to 22.1 percentage points]). Combination therapy yielded better outcomes over time on the Urogenital Distress Inventory and the Overactive Bladder Questionnaire (both P