Purpose of ReviewBiosimilars of the reference biologic therapeutics infliximab, etanercept, adalimumab, and rituximab are entering the market. Clinical and real-world data on the effects of reference → biosimilar switching are limited. This review was carried out to assess the current body of switching data.Recent FindingsFifty-three switching studies were identified. Infliximab publications covered CT-P13 (25 studies), SB2 (1), infliximab NK (1), and unspecified infliximab biosimilars (2). Etanercept publications covered SB4 (2) and GP2015 (2). Adalimumab publications covered ABP 501 (2) and SB5 (1). Rituximab publications covered CT-P10 (1). Efficacy and safety data generally showed no differences between patients who switched treatments versus those who did not. No differences were seen pre- and post-switch. Immunogenicity data were presented in 19/37 (51%) studies.SummaryAdditional data from switching studies of these therapies are still required, as is continuing pharma-covigilance. Switching should remain a case-by-case clinical decision made by the physician and patient on an individual basis supported by scientific evidence.Electronic supplementary materialThe online version of this article (doi:10.1007/s11926-017-0658-4) contains supplementary material, which is available to authorized users.

ObjectiveTo assess the incidence of anti-drug antibodies (ADA) in patients with rheumatoid arthritis (RA) treated with the TNF inhibitors etanercept (ETN), adalimumab (ADL), or infliximab (IFX), and determine the potential relationship with trough drug concentration, efficacy, and patient-reported outcomes.MethodsThis multi-national, non-interventional, cross-sectional study (NCT01981473) enrolled adult patients with RA treated continuously for 6–24 months with ETN, ADL, or IFX. ADA and trough drug concentrations were measured by independent assays ≤2 days before the next scheduled dose. Efficacy measurements included Disease Activity Score 28-joint count (DAS28), low disease activity (LDA), remission, and erythrocyte sedimentation rate (ESR). Targeted medical histories of injection site/infusion reactions, serum sickness, and thromboembolic events were collected.ResultsBaseline demographics of the 595 patients (ETN: n = 200; ADL: n = 199; IFX: n = 196) were similar across groups. The mean duration of treatment was 14.6, 13.5, and 13.1 months for ETN, ADL, and IFX, respectively. All ETN-treated patients tested negative for ADA, whereas 31.2% and 17.4% patients treated with ADL and IFX, respectively, tested positive. In ADL- or IFX-treated patients, those with ADA had significantly lower trough drug concentrations. There were negative correlations between trough drug levels and both CRP and ESR in ADL- and IFX-treated patients. DAS28-ESR LDA and remission rates were higher in patients without ADA. The rate of targeted medical events reported was low.ConclusionADA were detected in ADL- and IFX-treated but not ETN-treated patients. Patients without ADA generally showed numerically better clinical outcomes than those with ADA.Trial registrationThis study was registered on www.ClinicalTrials.gov (NCT01981473).

Biologics are vital to the management of patients with rheumatic and musculoskeletal diseases such as rheumatoid arthritis and other inflammatory and autoimmune conditions. Nevertheless, access to these highly effective treatments remains an unmet medical need for many people around the world. As patents expire for existing licensed biologic (originator) products, biosimilar products can be approved by regulatory authorities and enter clinical use. Biosimilars are highly similar copies of originator biologics approved through defined and stringent regulatory processes after having undergone rigorous analytical, non-clinical, and clinical evaluations. The introduction of high-quality, safe, and effective biosimilars has the potential to expand access to these important medicines. Biosimilars are proven to be similar to the originator biologic in terms of safety and efficacy and to have no clinically meaningful differences. In contrast, “intended copies” are copies of originator biologics that have not undergone rigorous comparative evaluations according to the World Health Organization recommendations, but are being commercialized in some countries. There is a lack of information about the efficacy and safety of intended copies compared with the originator. Furthermore, they may have clinically significant differences in formulation, dosages, efficacy, or safety. In this review, we explore the differences between biosimilars and intended copies and describe key concepts related to biosimilars. Familiarity with these topics may facilitate decision making about the appropriate use of biosimilars for patients with rheumatic and musculoskeletal diseases.

Atopic dermatitis (AD), the leading cause of skin-related burden of disease worldwide, is increasing in prevalence in developing countries of Asia, Africa, Latin America, and the Middle East. Although AD presents similarly across racial and ethnic groups as chronic and relapsing pruritic eczematous lesions, some features of the disease may be more or less prominent in patients with darker skin. Despite a similar presentation, consistent diagnostic criteria and consistent treatment guidelines are lacking. Because of these and other challenges, adherence to treatment guidelines is difficult or impossible. Previous studies have stated that many patients with AD receive ineffective or inappropriate care, such as oral antihistamines, oral corticosteroids, or traditional medicines, if they are treated at all; one study showed that approximately one-third of patients received medical care for their dermatologic condition; of those, almost three-quarters received inappropriate or ineffective treatment. In addition, other challenges endemic to developing countries include cost, access to care, and lack of specialists in AD. Furthermore, most of the available diagnostic criteria and treatment guidelines are based on European and North American populations and few clinical trials report the racial or ethnic makeup of the study population. Drug pharmacokinetics in varying ethnicities and adverse effects in different skin physiologies are areas yet to be explored. The objective of this review is to describe the diagnosis, treatment, and management of AD in developing countries in Asia, Africa, Latin America, and the Middle East; to discuss the differences among the countries; and to establish the unmet needs of patients with AD in them. The unmet medical need for treatment of AD in developing countries can be addressed by continuing to train medical specialists, improve Enhanced Digital Features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.9918782.

Objective: To determine the prevalence of diabetic peripheral neuropathic pain (DPNP) among South African adults with type 1 or type 2 diabetes. Methods: This cross-sectional study recruited patients with diabetes from 50 institutional/private clinics. DPNP was diagnosed using Douleur Neuropathique 4 (DN4) questionnaire (score !4). Health-related quality-of-life (HRQoL) and sleep were assessed with EQ-5D and Daily Sleep Interference Scale (DSIS), respectively. Results: Prevalence of DPNP was 30.3% (n ¼ 1046). Risk of DPNP was significantly increased in people aged 50-64 years (odds ratio [OR] 1.71, 95% confidence intervals [CI] 1.21, 2.41), with diabetes for !10 years (OR 1.55, 95% CI 1.15, 2.08), female patients (OR 1.58, 95% CI 1.18, 2.12), and black patients (OR 1.71, 95% CI 1.19, 2.46). Mean AE SD EQ-5D and DSIS scores were 0.84 AE 0.16 and 0.83 AE 1.90, respectively, in participants without DPNP versus 0.64 AE 0.25 and 3.62 AE 2.96, respectively, in those with DPNP.