US rheumatologists' beliefs and knowledge about biosimilars: a survey.

OBJECTIVES: We sought to evaluate perceptions of biosimilar products among US rheumatologists who prescribe TNF-α inhibitors, given that 10 TNF-α inhibitor biosimilars and two rituximab biosimilars have Food and Drug Administration (FDA) approval. METHODS: A 19-question self-administered online survey was conducted from 6 May to 1 June 2019, and fielded by WebMD, LLC. Rheumatologists (n = 9050) who were members of Medscape.com and its partner panels were invited to participate. Likert and other rating scales were used to collect responses, which were summarized descriptively. RESULTS: Responses were obtained from 320 board-certified US rheumatologists, 85% of whom were fellows of the ACR. Nearly all respondents were familiar with the FDA definition of a biosimilar product and were aware that an infliximab biosimilar was FDA approved; fewer realized that adalimumab, etanercept and rituximab biosimilars were also FDA approved. Most respondents (84%) were aware that an approved biosimilar was not automatically deemed interchangeable by the FDA. Rheumatologists were more likely to initiate biosimilar treatment for a biologic treatment-naïve patient with RA (73%) than they were to switch to the biosimilar for a patient with RA doing well on the reference product (35%). CONCLUSIONS: The results of this survey suggest that US rheumatologists have a good understanding and acceptance of biosimilar products, particularly for the initiation of treatment in biologic-naïve individuals. They were hesitant to switch from a reference product to a biosimilar for a patient doing well on the reference product. Additional education on biosimilars is required to help inform treatment decisions by rheumatologists. A plain language summary of this article has been uploaded as supplementary material, available at Rheumatology online.

Hydroxychloroquine and Chloroquine in COVID-19: A Survey of Prescription Patterns Among Rheumatologists.

OBJECTIVE: With hydroxychloroquine (HCQ) and chloroquine (CQ) emerging as potential therapies for coronavirus disease 2019 (COVID-19), shortages have been reported. We aimed to understand how rheumatologists, one of the most common prescribers of HCQ/CQ, prescribed these medications to manage COVID-19 and to understand if their patients are affected by shortages. METHODS: Between April 8 and April 27, 2020, an online survey was distributed to a convenience sample of rheumatologists who practice medicine in a diverse range of settings globally, resulting in 506 responses. Adjusted Poisson regression models were calculated. RESULTS: Only 6% of respondents prescribed HCQ/CQ for COVID-19 prophylaxis, and only 12% for outpatient treatment of COVID-19. Compared to the United States, the likelihood of prescribing HCQ/CQ for prophylaxis was higher in India (adjusted risk ratio [aRR], 6.7; 95% confidence interval [CI], 2.7-16.8; p < 0.001). Further, compared to the United States and those with 1 to 5 years of experience, rheumatologists in Europe (aRR, 2.9; 95% CI, 1.6-5.3; p < 0.001) and those with 10+ years of experience (11-20 years: aRR, 2.5; 95% CI, 1.2-5.3; p = 0.015; 21+ years: aRR = 3.3; 95% CI, 1.4-7.4; p = 0.004) had a higher likelihood of prescribing HCQ/CQ for outpatient treatment. Of note, 71% of all rheumatologists reported that their patients were directly affected by HCQ/CQ shortages. CONCLUSION: The results suggest that only a small percentage of rheumatologists are prescribing HCQ/CQ for prophylaxis or outpatient treatment of COVID-19. Medication shortages experienced by large numbers of autoimmune disease patients are concerning and should play a role in decisions, especially given poor efficacy data for HCQ/CQ in COVID-19.

Short-term costs associated with non-medical switching in autoimmune conditions.

OBJECTIVES: To estimate short-term costs associated with non-medical switch (NMS) from originator biologics to biosimilars among stable patients with autoimmune conditions in rheumatology, gastroenterology, and dermatology from a US provider's and third-party payer's perspective. METHODS: An economic model was constructed to estimate switching costs related to physician time and healthcare resource utilisation (HRU) at the initial NMS visit and over 3 months. The proportion of patients with relevant conditions treated with originators and expected NMS rate, physician time, HRU, and payer reimbursement were derived from a physician survey. Switching costs were estimated for a practice of 1,000 patients with relevant conditions by therapeutic area and for an insurance plan with 1 million individuals by therapeutic area and all areas combined. Switching cost drivers were assessed with one-way sensitivity analyses. RESULTS: Physicians expected extra 6 minutes for the NMS visit and 22 minutes over 3 months; NMS rates of 14.4%, 15.5%, and 17.7%; and 11.3%, 16.2%, and 33.2% of time not reimbursed for gastroenterology, rheumatology, and dermatology, respectively. The total switching costs for payer's were $771,460 (for n = 3,609 patients with an NMS rate of 16.6%), mostly due to follow-up visits and additional laboratory tests/procedures. In sensitivity analyses, the NMS rate was the main cost driver. Increasing the NMS rate to 25% and 50% increased payer's total switching costs to $1.19 and $2.39 million, respectively. CONCLUSIONS: Originator-to-biosimilar NMS in stable patients with autoimmune conditions could result in considerable switching costs for both providers and payers.

Comparison of patient and physician perspectives in the management of rheumatoid arthritis: results from global physician- and patient-based surveys.

BACKGROUND: In order to better understand the perspectives of patients and physicians regarding the treatment and management of rheumatoid arthritis (RA), we present and compare results from a patient-based and a physician-based survey developed by the RA NarRAtive advisory panel. METHODS: The RA NarRAtive initiative is directed by a global advisory panel of 39 healthcare providers and patient organization leaders from 17 countries. A survey of patients self-reporting a diagnosis of RA and a physician-based survey, designed by the advisory panel, were fielded online by Harris Poll from September 2014 to April 2016, and from August 2015 to October 2015, respectively. RESULTS: We present findings from 1805 patients whose RA was primarily managed by a rheumatologist, and 1736 physicians managing patients with RA. Results confirmed that RA carries a substantial disease burden; half of the patients surveyed reported stopping participation in certain activities as a result of their disease. While 90% of physicians were satisfied with their communications with their patients regarding RA treatment, 61% of patients felt uncomfortable raising concerns or fears with their physician. Of the patients providing responses, 52% felt that improved dialogue/discussion would optimize their RA management, and 68% of physicians wished that they and their patients talked more about their RA goals and treatment. Overall, 88% of physicians agreed that patients involved in making treatment decisions tend to be more satisfied with their treatment experience. CONCLUSION: The results of these surveys highlight the impact of RA on patients, and a discrepancy between patient and physician views on communication. Further research, focused on improving patient-physician dialogue, shared goal-setting, and treatment planning, is needed.

Down-titration of biologics for the treatment of rheumatoid arthritis: a systematic literature review.

Biologic therapies have improved the management of rheumatoid arthritis (RA) and the treat-to-target approach has resulted in many patients achieving remission. In the current treatment landscape, clinicians have begun considering dose reduction/tapering for their patients. Rheumatology guidelines in Asia, Europe, and the United States include down-titration of biologics but admit that the level of evidence is moderate. We conducted a systematic literature review to assess the published studies that evaluate down-titration of biologics in RA. The published literature was searched for studies that down-titrated the following biologics: abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, and tocilizumab. Eligible studies included randomized controlled trials (RCTs), non-RCTs, observational, and pharmacoeconomic studies. The outcomes of interest were (1) efficacy and health-related quality of life, (2) disease flares, and (3) impact on cost. Eleven full-text publications were identified; only three were RCTs. Study results suggest that dosing down may be an option in many patients who have achieved remission or low disease activity. However, some patients are likely to experience a disease flare. Across the studies, the definition of disease flare and the down-titration criteria were inconsistent, making it difficult to conclude which patients may be appropriate and when to attempt down-titration. Studies have evaluated the practice of dosing down biologic therapy in patients with RA; however, a relatively small number of RCTs have been published. Although down-titration may be an option for some patients in LDA or remission, additional RCTs are needed to provide guidance on this practice.

Sex differences in gout characteristics: tailoring care for women and men.

BACKGROUND: To characterize the differences between women and men with gout. METHODS: We analyzed a US national cohort of gout patients cared for by rheumatologists. RESULTS: Compared with the 1012 men with gout, women with gout (n = 262) were older (71 vs. 61 years, p < 0.001) and had a greater burden of comorbid conditions (p < 0.001 for hypertension, diabetes, renal disease and obesity). Risk factors for gout differed with women more often taking diuretics (p < 0.001), while men more frequently had dietary triggers (p < 0.05). CONCLUSIONS: The profiles of women and men with gout are markedly different, suggesting a need to tailor treatment recommendations.

Discontinuation of disease-modifying anti-rheumatic drugs and clinical outcomes in the Rheumatoid Arthritis DMARD Intervention and Utilisation Study 2 (RADIUS 2).

OBJECTIVES: The purpose of this analysis was to examine discontinuation and reasons for discontinuation from disease-modifying anti-rheumatic (DMARD) therapies in the RADIUS 2 registry, a long-term, open-label, observational study of patients with moderate to severe rheumatoid arthritis (RA). METHODS: Patients who participated in RADIUS 2 initiated etanercept (ETN) therapy at study entry and were followed for 5 years. In this post hoc analysis, patients who had received ETN continuously from entry to month 4 were categorised by treatment at month 4: ETN monotherapy, ETN+methotrexate (MTX), ETN+MTX+other DMARDs (OTH), or ETN+OTH. Outcomes were assessed at month 4 and at the time of any subsequent treatment change, and included Clinical Disease Activity Index (CDAI) and Health Assessment Questionnaire Disability Index (HAQ-DI). RESULTS: Of 3,484 patients analysed (982 ETN; 1,356 ETN+MTX; 537 ETN+MTX+OTH; 609 ETN+OTH), baseline demographic and clinical characteristics were similar across treatments. No treatment change occurred in 62.3%, 49.9%, 33.3%, and 37.1% of ETN, ETN+MTX, ETN+MTX+OTH, and ETN+OTH patients, respectively. The mean time on therapy from month 4 was longer for patients receiving ETN (23.3 months) or ETN+MTX (23.7 months) than those receiving ETN+MTX+OTH (18.0 months) or ETN+OTH (18.3 months). The greatest improvements in CDAI and HAQ-DI were seen in patients who continued on ETN. The most common reasons for discontinuing DMARD therapy were cost and ineffective treatment. CONCLUSIONS: Most patients who had received ≥4 months of ETN continued on ETN throughout the 5-year observation period. Patients with greatest clinical and disability improvements tended to continue on ETN.

The rheumatoid arthritis treat-to-target trial: a cluster randomized trial within the Corrona rheumatology network.

BACKGROUND: The treat-to-target (T2T) approach to the care of patients with rheumatoid arthritis involves using validated metrics to measure disease activity, frequent follow-up visits for patients with moderate to high disease activity, and escalation of therapy when patients have inadequate therapeutic response as assessed by standard disease activity scores. The study described is a newly launched cluster-randomized behavioral intervention to assess the feasibility and effectiveness of the T2T approach in US rheumatology practices. It is designed to identify patient and provider barriers to implementing T2T management. This initial paper focuses on the novel study design and methods created to provide these insights. METHODS/DESIGN: This trial cluster-randomizes rheumatology practices from the existing Corrona network of private and academic sites rather than patients within sites or individual investigators to provide either T2T or usual care (UC) for qualified patients who meet the 2010 revised American College of Rheumatology criteria for the diagnosis of rheumatoid arthritis and have moderate to high disease activity. Specific medication choices are left to the investigator and patient, rather than being specified in the protocol. Enrollment is expected to be completed by the end of 2013, with 30 practices randomized and enrolling a minimum of 530 patients. During the 12-month follow-up, visits are mandated as frequently as monthly in patients with active disease in the T2T group and every 3 months for the UC group. Safety data are collected at each visit. The coprimary endpoints include a comparison of the proportion of patients achieving low disease activity in the T2T and UC groups and assessment of the feasibility of implementing T2T in rheumatology practices, specifically assessment of the rates of treatment acceleration, frequency of visits, time to next visit conditional on disease activity, and probability of acceleration conditional on disease activity in the 2 groups. DISCUSSION: This cluster-randomized behavioral intervention study will provide valuable insights on the outcomes and feasibility of employing a T2T treatment approach in clinical practice in the United States. TRIAL REGISTRATION: NCT01407419.

Impact of the COVID-19 Pandemic on People Living with Rheumatoid Arthritis: Experiences and Preferences in Accessing Healthcare Across Five Countries.

INTRODUCTION: The global coronavirus 2019 (COVID-19) pandemic created many challenges in healthcare provision. This study aimed to evaluate the global impact of the COVID-19 pandemic on people living with rheumatoid arthritis (RA). METHODS: The RA Narrative COVID-19 survey was conducted online among people with RA who resided in Brazil, Canada, France, Japan, and the US from August to September 2021. The survey examined disease management, healthcare access and experiences, and participant preferences for interactions with their doctor. RESULTS: Overall, 500 participants completed the survey: 100 each resided in Brazil, Canada, France, Japan, and the US. Emotional well-being was the aspect of disease management most reported to be negatively impacted by the pandemic (55% of participants); 'having more anxiety and/or stress' during the pandemic was the top factor that made controlling RA symptoms more difficult (49% of participants). In comparison, the top factor that made controlling RA symptoms easier was 'having a less busy schedule' (35% of participants). More participants had virtual appointments during versus pre-pandemic (53% vs. 13%, respectively) and participants were equally satisfied with the overall quality of care received via virtual and in-person appointments (76% of participants were 'satisfied' or 'very satisfied' with both). However, participants generally preferred in-person over virtual appointments, except for prescription refills, for which preferences were similar (39% vs. 36%, respectively). CONCLUSIONS: This survey suggests that the COVID-19 pandemic did negatively impact some aspects of disease management for people living with RA but had positive impacts on the utilization of virtual care. Although participants generally preferred in-person appointments, these results position virtual care as an appropriate means for routine follow-ups.

Blocking the effects of interleukin-6 in rheumatoid arthritis and other inflammatory rheumatic diseases: systematic literature review and meta-analysis informing a consensus statement.

BACKGROUND: Suppression of the immunoinflammatory cascade by targeting interleukin 6 (IL-6) mediated effects constitutes a therapeutic option for chronic inflammatory diseases. Tocilizumab is the only IL-6 inhibitor (IL-6i) licensed for rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), but also other agents targeting either IL-6 or its receptor are investigated in various indications. OBJECTIVE: To review published evidence on safety and efficacy of IL-6i in inflammatory diseases. METHODS: We performed systematic literature searches in Medline and Cochrane, screened EULAR and American College of Rheumatology meeting-abstracts, and accessed http://www.clinicaltrials.gov. RESULTS: Comprehensive evidence supports the efficacy of tocilizumab in RA in DMARD-naïve patients, and after DMARD- and TNFi-failure. Randomised comparisons demonstrate superiority of tocilizumab in JIA, but not ankylosing spondylitis (AS). Other indications are currently investigated. Additional IL-6i show similar efficacy; safety generally appears acceptable. CONCLUSIONS: IL-6i is effective and safe in RA and JIA, but not in AS. Preliminary results in other indications need substantiation.

Consensus statement on blocking the effects of interleukin-6 and in particular by interleukin-6 receptor inhibition in rheumatoid arthritis and other inflammatory conditions.

BACKGROUND: Since approval of tocilizumab (TCZ) for treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), interleukin 6 (IL-6) pathway inhibition was evaluated in trials of TCZ and other agents targeting the IL-6 receptor and ligand in various RA populations and other inflammatory diseases. This consensus document informs on interference with the IL-6 pathway based on evidence and expert opinion. METHODS: Preparation of this document involved international experts in RA treatment and RA patients. A systematic literature search was performed that focused on TCZ and other IL6-pathway inhibitors in RA and other diseases. Subsequently, incorporating available published evidence and expert opinion, the steering committee and a broader expert committee (both including RA patients) formulated the current consensus statement. RESULTS: The consensus statement covers use of TCZ as combination- or monotherapy in various RA populations and includes clinical, functional and structural aspects. The statement also addresses the second approved indication in Europe JIA and non-approved indications. Also early phase trials involving additional agents that target the IL-6 receptor or IL-6 were evaluated. Safety concerns, including haematological, hepatic and metabolic issues as well as infections, are addressed likewise. CONCLUSIONS: The consensus statement identifies points to consider when using TCZ, regarding indications, contraindications, screening, dose, comedication, response evaluation and safety. The document is aimed at supporting clinicians and informing patients, administrators and payers on opportunities and limitations of IL-6 pathway inhibition.

An online survey among US patients with immune-mediated conditions: Attitudes about biosimilars.

BACKGROUND: Few surveys about biosimilars have been conducted among US patients. OBJECTIVE: To evaluate attitudes about biosimilars among patients with rheumatoid arthritis (RA), psoriasis and/or psoriatic arthritis (PsO/A), and/or inflammatory bowel disease (IBD). METHODS: WebMD, LLC fielded a 16-item online survey to members of the US Dynata consumer panel meeting these criteria: aged 18 years or older; self-reported specialist diagnosis of RA, PsO/A, or IBD of at least 1 year; and not currently receiving an infliximab biosimilar. A quota of 500 was set, stratified by region and condition. The survey was exempt by the institutional review board, exploratory, and not registered. RESULTS: Overall, 44% (n = 221) of patients were on a biologic; 56% (n = 279) were not on a biologic (40% [n = 199] were biologic naive and 16% [n = 80] used biologics in the past). Among all patients, 66% were unaware of biosimilars and 24% were aware (10% unsure). After being shown the US Food and Drug Administration definition of a biosimilar, main concerns were side effects (59%), long-term safety (50%), and not knowing a lot (46%). Among current users, 43% would switch to a biosimilar and 26% would not (32% unsure). Of those unwilling to switch, 51% were concerned about side effects, 42% about financial support, and 40% about efficacy. When those not on a biologic were asked if their doctor prescribed an original anti-tumor necrosis factor α but their insurance required its biosimilar, 49% would switch and 8% would not (43% unsure). 51% of patients surveyed thought pharmacist-level substitution of an interchangeable biosimilar was acceptable with notification. Survey findings were consistent among the RA, PsO/A, and IBD subgroups. CONCLUSIONS: Although two-thirds of patients surveyed were unaware of biosimilars, the majority were potentially receptive to biosimilar treatment after being provided with the definition of a biosimilar. Patients expressed a desire to know more about biosimilars in general, how they compare with original biologics, their benefits, and cost. DISCLOSURES: This study was funded by Boehringer Ingelheim Pharmaceuticals Inc. (BIPI). WebMD, LLC, fielded the survey. BIPI was given the opportunity to review the article for medical and scientific accuracy and intellectual property considerations. Dr Gibofsky is a consultant/advisor for AbbVie Inc., Biosplice Therapeutics, Lilly, Novartis Pharmaceuticals Corporation, and Pfizer Inc., and he is on the speakers' bureau for AbbVie Inc., Amgen, Lilly, and Pfizer Inc., and has stock ownership in AbbVie Inc., Amgen, Bristol-Myers Squibb Company, Horizon Pharma plc, and Pfizer Inc. Dr Peyrin-Biroulet reports that he has received personal consulting fees from Merck Sharp & Dohme, AbbVie, Janssen, Takeda, Celltrion, Pfizer, Bristol-Myers Squibb Company, Pharmacosmos, Shire, Genentech, Mitsubishi, Ferring, Norgine, Tillots, Vifor, UCB-Pharma, Hospira, BIPI, and Lilly. Dr McCabe is an employee of BIPI. Dr McGrath was an employee of BIPI at the time the survey was conducted. Mr Jacobson, Mr Franklin, and Ms O'Hara-Levi report no disclosures.

Prescriber Perspectives on Biosimilar Adoption and Potential Role of Clinical Pharmacology: A Workshop Summary.

The approval and adoption of biosimilar products are essential to contain increasing healthcare costs and provide more affordable choices for patients. Despite steady progress in the number of the US Food and Drug Administration (FDA) biosimilar approvals over the years, biosimilar adoption in the United States has been slow and gradual, largely driven by payers rather than clinicians. In order to better understand the barriers to biosimilar adoption in the clinic, the University of Maryland Center of Excellence in Regulatory Science and Innovation (M-CERSI) and the FDA jointly hosted a virtual workshop on April 13, 2022, titled "Biosimilars: A Decade of Experience and Future Directions - Strategies for Improving Biosimilar Adoption and the Potential Role of Clinical Pharmacology." This summary documents the experiences of four leading academic clinicians with specialties in oncology, rheumatology, gastroenterology, and endocrinology and their perspectives on how to increase biosimilar adoption, including the role of clinical pharmacology. Besides systemic changes in pricing and reimbursement, there is a need for additional education of a broad range of providers, including advanced care practitioners, and patients themselves. Educational efforts highlighting the rigor of the studies that support the approval of biosimilars-including the clinical pharmacology studies-and the benefits of biosimilars, can play a major role in improving biosimilar acceptance.

A comparative effectiveness study of adalimumab, etanercept and infliximab in biologically naive and switched rheumatoid arthritis patients: results from the US CORRONA registry.

PURPOSE: To compare the effectiveness of anti-tumour necrosis factor (TNF) agents in biologically naive and 'switched' rheumatoid arthritis (RA) patients. METHODS: RA patients enrolled in the CORRONA registry newly prescribed adalimumab (n=874), etanercept (n=640), or infliximab (n=728) were stratified based on previous anti-TNF use. Clinical effectiveness at 6, 12 and 24 months was examined using the modified American College of Rheumatology response criteria (mACR20/50/70) and achievement of remission (28-joint disease activity score (DAS28) and clinical disease activity index (CDAI)) in unadjusted and adjusted analyses. The persistence of anti-TNF treatment was examined using Cox proportional hazard models. RESULTS: Among 2242 patients (1475 biologically naive, 767 switchers), mACR20, 50 and 70 responses were similar (p>0.05) for adalimumab, etanercept and infliximab at all time points, as were rates of CDAI and DAS28 remission (p>0.05). Response and remission outcomes were consistently inferior for switched versus biologically naive patients. The adjusted OR for achieving an mACR20 response was 0.54 (95% CI 0.38 to 0.76) in first-time switchers and 0.42 (95% CI 0.23 to 0.78) in second-time switchers versus biologically naive patients at 6 months. The adjusted OR for achieving DAS28 remission were 0.29 (95% CI 0.15 to 0.58) for first-time switchers and 0.26 (95% CI 0.08 to 0.84) for second-time switchers. Persistence was higher in biologically naive patients, for whom persistence was highest with infliximab. CONCLUSIONS: No differences in rates of drug response or remission were observed among the three anti-TNF. Infliximab was associated with greater persistence in biologically naive patients. Response, remission and persistence outcomes were diminished for patients who switched anti-TNF.

A phase 2 study evaluating the efficacy and safety of a novel, proprietary, nano-formulated, lower dose oral diclofenac.

BACKGROUND: Safety concerns associated with nonsteroidal anti-inflammatory drugs (NSAIDs) have prompted the development of new formulations that minimize adverse events (AEs) and maintain efficacy. OBJECTIVES: To determine the analgesic efficacy and safety of an investigational, proprietary, nano-formulated, oral diclofenac (nano-formulated diclofenac) compared with placebo in subjects with acute dental pain. METHODS: A Phase 2, multisite, randomized, double-blind, single-dose, parallel-group, active- and placebo-controlled study was carried out in 202 subjects (18-50 years old) who had extraction of ≥2 third molars (≥1 had to be a fully or partially impacted mandibular third molar) and experienced moderate to severe pain intensity ≤6 hours postsurgery (NCT00985439). Subjects received nano-formulated diclofenac 35 mg or 18 mg, celecoxib 400 mg, or placebo. The primary efficacy variable was the sum of total pain relief (TOTPAR) over 0-12 hours (TOTPAR-12) after Time 0. Secondary end points included TOTPAR over 0-4 hours (TOTPAR-4), TOTPAR over 0-8 hours (TOTPAR-8), and time to onset of analgesia. RESULTS: Mean ± standard deviation TOTPAR-12 for nano-formulated diclofenac 35 mg and 18 mg, celecoxib, and placebo were 16.81 ± 12.76, 17.76 ± 13.76, 14.61 ± 15.05, and 5.65 ± 11.53, respectively (P < 0.001, nano-formulated diclofenac compared with placebo). Similar improvements were observed for TOTPAR-4, TOTPAR-8, mean time to first perceptible pain relief (P < 0.001), and peak relief (P < 0.05). Celecoxib treatment was not statistically different than placebo for these latter two parameters. Treatment-emergent AEs were similar across all treatment groups. CONCLUSIONS: Lower dose, nano-formulated diclofenac demonstrated good overall efficacy, prompt pain relief, and was well tolerated. These data suggest lower dose nano-formulated NSAIDs could be effective for acute pain and may potentially improve safety and tolerability as a result of using a lower overall dose.

Overview of biosimilars for immune-mediated inflammatory diseases: summary of current evidence.

Biosimilars offer the potential to deliver substantial cost savings in biologic therapy and to contribute to increased patient access to biologic treatments, both of which are particularly relevant for immune-mediated inflammatory diseases, given the number of patients affected by and receiving treatment for these conditions. For the United States to benefit from bringing biosimilar pipeline products to the market, legal and price-related barriers to competition must be addressed. In addition, education of prescribers, patients, payers, and providers is essential to increase uptake as biosimilars reach the market. This article discusses biosimilars currently available for the treatment of immune-mediated inflammatory diseases in the United States, reviews the main concepts related to regulatory approval of biosimilars by the FDA, and considers potential barriers to the uptake of biosimilars.

Provider and patient knowledge gaps on biosimilars: insights from surveys.

Beyond the legal and regulatory limitations associated with biosimilar availability in the United States, the adoption of biosimilars is contingent on the willingness of health care providers (HCPs) to prescribe them and of patients to accept them. In this dynamic market, it is of paramount importance to understand the current awareness, attitudes, and preferences of a broad spectrum of stakeholders if uptake of biosimilars is to be optimized. In this article, we highlight knowledge gaps among US HCPs and patients regarding biosimilars for immune-mediated inflammatory diseases as assessed in published survey literature over the last 5 years. Although HCP familiarity and understanding of biosimilars appears to have improved over the last 5 years, survey data suggest that some physicians and pharmacists still approach use of biosimilars with caution owing to concerns regarding nonmedical switching, interchangeability, pharmacist-led substitution, and the extent of any cost savings. Patients understand the potential cost benefits of biosimilars but share many of the HCPs' concerns. A large majority of patients were also concerned that biosimilars would not treat their disease as well as the reference product and that switching may cause more adverse effects. Consequently, nonmedical switching is a major concern for patients, with the majority reporting that they would attempt to avoid a switch. Although patients trust their physicians' treatment recommendations and express confidence in biosimilars, they have mixed views on automatic substitution by pharmacists. The areas of concern identified can be used to guide further education programs for HCPs and patients, and, in doing so, improve biosimilar uptake.

Biosimilars for immune-mediated inflammatory diseases: a managed care perspective.

Biosimilars hold the promise of substantial potential cost savings in health care with no compromise in the efficacy and safety of treatment. Despite this, their adoption in the United States has been substantially slower than might have been expected. In addition to patient and provider barriers to their widespread adoption as discussed in the second article in this supplement, additional potential barriers to their use are inherent to the current US health care system. In this article, we examine biosimilar agents from a managed care perspective and discuss some of the reasons behind their delayed adoption in the United States.

Methotrexate versus leflunomide in rheumatoid arthritis: what is new in 2011?

PURPOSE OF REVIEW: To review the recent efficacy and safety data comparing methotrexate (MTX) and leflunomide (LEF) monotherapy, in combination with biologic therapies and in combination with each other. RECENT FINDINGS: MTX is the 'anchor drug' in all rheumatoid arthritis treatment strategies. Patients with contraindications to or intolerance of this drug pose a challenge to the treating physician. Recent studies have re-examined LEF as an alternative to MTX and demonstrated comparable clinical and radiographic efficacy both as monotherapy and in combination with certain biologic agents (tumor necrosis factor inhibitors and rituximab). Safety data, however, are less conclusive. Though some studies have shown greater withdrawal rates with LEF, the incidence of infection and elevated transaminases have been comparable. There are few new data examining the previously demonstrated added benefit of combination MTX+LEF over either alone. The safety profile of this combination, however, has been re-examined in several studies, with conflicting results. Although two meta-analyses and two small retrospective studies have demonstrated a safety profile similar to that of MTX monotherapy, data from a large population study suggested a greater degree of hepatotoxicity with combination. SUMMARY: LEF offers an alternative with comparable efficacy to MTX as both monotherapy and, as preliminary data suggest, in combination with certain biologics agents. Addition of LEF to MTX in rheumatoid arthritis patients who have failed MTX monotherapy has added therapeutic benefit. Safety data on LEF compared to MTX are less conclusive. All patients on LEF, and particularly those on combined LEF+MTX, should be monitored closely for hepatotoxicity.

Treating Rheumatoid Arthritis to Target: multinational recommendations assessment questionnaire.

AIM: To measure the level of agreement and application of 10 international recommendations for treating rheumatoid arthritis (RA) to a target of remission/low disease activity. METHODS: A 10-point Likert scale (1=fully disagree, 10=fully agree) measured the level of agreement with each of 10 recommendations. A 4-point Likert scale (never, not very often, very often, always) assessed the degree to which each recommendation was being applied in current daily practice. If respondents answered 'never' or 'not very often', they were asked whether they would change their practice according to the particular recommendation. RESULTS: A total of 1901 physicians representing 34 countries participated. Both agreement with and application of recommendations was high. With regard to application of recommendations in daily practice, the majority of responses were 'always' and 'very often'. A significant percentage of participants who were currently not applying these recommendations in clinical practice were willing to change their practice according to the recommendations. CONCLUSION: The results of this survey demonstrated great support of 'Treating RA to Target' recommendations among the international rheumatology community. Additional efforts may be needed to encourage application of the recommendations among certain clinicians who are resistant to changing their practice.