Multiple switching between the biosimilar adalimumab PF-06410293 and reference adalimumab in patients with active rheumatoid arthritis: a phase 3, open-label, randomised, parallel-group study.

BACKGROUND: An adalimumab biosimilar with an interchangeability designation could increase access to effective treatment for more patients. We aimed to assess the interchangeability of adalimumab biosimilar PF-06410293 (adalimumab-afzb) and reference adalimumab using a multi-switch study design. METHODS: We did an open-label, randomised, parallel-group study at 61 community (n=29), hospital (n=12), and academic (n=20) sites in ten countries (Bulgaria, Bosnia and Herzegovina, Czech Republic, Lithuania, Poland, Russia, Serbia, South Africa, Ukraine, and USA). Eligible patients were aged 18-70 years and met the 2010 American College of Rheumatology-European League Against Rheumatism classification criteria for rheumatoid arthritis for at least 4 months with moderately to severely active rheumatoid arthritis, based on their physician's evaluation. Eligible patients had been receiving methotrexate for at least 12 weeks and been on a stable dose for at least 4 weeks before the first dose of study medication. All patients received subcutaneous reference adalimumab (40 mg/0·4 mL [100 mg/mL] every 2 weeks) for 10 weeks before randomisation. At week 10, patients were randomly assigned (1:1) to either three switches between subcutaneous reference adalimumab (40 mg/0·4 mL [100 mg/mL] every 2 weeks) and adalimumab-afzb (40 mg/0·8 mL [50 mg/mL] every 2 weeks; switching group), or continuous dosing with subcutanous reference adalimumab (40 mg/0·4 mL [100 mg/mL] every 2 weeks; non-switching group) with stratification by bodyweight groups. Patients, investigators, and site personnel were not masked to treatment allocation. Primary endpoints were maximum observed serum concentration (Cmax) and area under plasma concentration-time curve (AUCτ) during weeks 30-32 in the pharmacokinetic population. Interchangeability was based on geometric mean ratios and corresponding 90% CIs within prespecified equivalence margins of 80-125% for both primary endpoints. Safety was analysed in all patients who received at least one dose of adalimumab-afzb or reference adalimumab. This trial is registered with ClinicalTrials.gov, NCT04230213. FINDINGS: Of the 569 patients assessed for eligibility between Jan 13, 2020, and June 22, 2021, 445 were enrolled, and 427 completed the first 10 weeks and were randomly assigned (213 to the switching group and 214 to the non-switching group). Participants had a median age of 56 years (IQR 46-63), 354 (83%) of 427 patients were women and 73 (17%) were men, and 422 (99%) were White. In the pharmacokinetic population (n=380), no clinically meaningful differences were observed in mean steady-state pharmacokinetic parameters between the switching and non-switching groups (geometric mean AUC 2237 µg × h/mL in the switching group and 2125 µg × h/mL in the non-switching group; Cmax 8·21 µg/mL in the switching group and 8·00 µg/mL in the non-switching group). Geometric mean ratios and 90% CIs for AUCτ (105·31, 89·16-124·39) and Cmax (102·56, 89·78-117·17) were within prespecified equivalence margins. No meaningful differences were observed in the proportion of patients who had serious adverse events (three [1%] of 213 patients in the switching group vs eight [4%] of 214 patients in the non-switching group), grade 3 or higher adverse events of special interest, discontinuations due to adverse events (eight [4%] vs nine [4%]), or immunogenic reactions in antidrug antibody-positive patients. No deaths were reported during the study. INTERPRETATION: The risk of multiple switches between reference adalimumab and adalimumab-afzb with respect to diminished efficacy (using pharmacokinetics as a surrogate) or safety is not greater than the risk of using reference adalimumab alone. FUNDING: Pfizer. VIDEO ABSTRACT.

A global perspective on the challenges and opportunities in learning about rheumatic and musculoskeletal diseases in undergraduate medical education : White paper by the World Forum on Rheumatic and Musculoskeletal Diseases (WFRMD).

Rheumatic and musculoskeletal diseases (RMDs) encompass a spectrum of degenerative, inflammatory conditions predominantly affecting the joints. They are a leading cause of disability worldwide and an enormous socioeconomic burden. However, worldwide deficiencies in adult and paediatric RMD knowledge among medical school graduates and primary care physicians (PCPs) persist. In October 2017, the World Forum on Rheumatic and Musculoskeletal Diseases (WFRMD), an international think tank of RMD and related experts, met to discuss key challenges and opportunities in undergraduate RMD education. Topics included needs analysis, curriculum content, interprofessional education, teaching and learning methods, implementation, assessment and course evaluation and professional formation/career development, which formed a framework for this white paper. We highlight a need for all medical graduates to attain a basic level of RMD knowledge and competency to enable them to confidently diagnose, treat/manage or refer patients. The importance of attracting more medical students to a career in rheumatology, and the indisputable value of integrated, multidisciplinary and multiprofessional care are also discussed. We conclude that RMD teaching for the future will need to address what is being taught, but also where, why and to whom, to ensure that healthcare providers deliver the best patient care possible in their local setting.

Common language description of the term rheumatic and musculoskeletal diseases (RMDs) for use in communication with the lay public, healthcare providers and other stakeholders endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).

A European League Against Rheumatism-American College of Rheumatology working group consisting of practising and academic rheumatologists, a rheumatology researcher and a patient representative created a succinct general statement describing rheumatic and musculoskeletal diseases (RMDs) in adults and children in language that can be used in conversations with the lay public, media, healthcare providers and other stakeholders. Based on the literature review, several elements were deemed important for inclusion in the description of RMDs. First, RMDs encompass many different diseases that can affect individuals at any age, including children. Second, there are various pathophysiological pathways underlying different RMDs. Third, the impact of RMDs on individuals and society should be emphasised. The working group agreed that the language should be comprehensible to the lay public. Thus, the following description of RMDs has been developed: 'Rheumatic and musculoskeletal diseases (RMDs) are a diverse group of diseases that commonly affect the joints, but can affect any organ of the body. There are more than 200 different RMDs, affecting both children and adults. They are usually caused by problems of the immune system, inflammation, infections or gradual deterioration of joints, muscles and bones. Many of these diseases are long term and worsen over time. They are typically painful and limit function. In severe cases, RMDs can result in significant disability, having a major impact on both quality of life and life expectancy.' This description can be used by rheumatology groups, researchers and those who work in advocacy and education related to RMDs.

Common Language Description of the Term Rheumatic and Musculoskeletal Diseases (RMDs) for Use in Communication With the Lay Public, Healthcare Providers, and Other Stakeholders Endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).

A European League Against Rheumatism-American College of Rheumatology working group consisting of practicing and academic rheumatologists, a rheumatology researcher, and a patient representative created a succinct general statement describing rheumatic and musculoskeletal diseases (RMDs) in adults and children in language that can be used in conversations with the lay public, media, healthcare providers, and other stakeholders. Based on the literature review, several elements were deemed important for inclusion in the description of RMDs. First, RMDs encompass many different diseases that can affect individuals at any age, including children. Second, there are various pathophysiological pathways underlying different RMDs. Third, the impact of RMDs on individuals and society should be emphasized. The working group agreed that the language should be comprehensible to the lay public. Thus, the following description of RMDs has been developed: "Rheumatic and musculoskeletal diseases (RMDs) are a diverse group of diseases that commonly affect the joints, but can affect any organ of the body. There are more than 200 different RMDs, affecting both children and adults. They are usually caused by problems of the immune system, inflammation, infections, or gradual deterioration of joints, muscles, and bones. Many of these diseases are long term and worsen over time. They are typically painful and limit function. In severe cases, RMDs can result in significant disability, having a major impact on both quality of life and life expectancy." This description can be used by rheumatology groups, researchers, and those who work in advocacy and education related to RMDs.

Intra-articular hyaluronans: a review of product-specific safety profiles.

BACKGROUND AND OBJECTIVES: Intra-articular (IA) hyaluronans (HAs) are indicated for pain relief of osteoarthritis (OA) of the knee. Hyalgan (sodium hyaluronate), Supartz (sodium hyaluronate), and Synvisc (hylan G-F 20) are Food and Drug Administration-approved HA products. They are derived from rooster combs; Hyalgan and Supartz are naturally derived (unmodified); Synvisc is chemically modified to increase its molecular weight. This article reviews and updates the safety data for IA HAs used for the treatment of knee OA. METHODS: References were taken from Medline through July 2002; respective product information services and information from the searchable United States Food and Drug Administration Manufacturer and User Facility Device Experience Database also were used. RESULTS: All products demonstrated favorable safety profiles in clinical trials and practice compared to other standard therapies for management of OA knee pain. The most common adverse event associated with HAs is mild injection site pain and swelling. Each product has had rare reports of pseudogout and anaphylactoid reactions. Product-specific adverse events, severe acute inflammatory reactions (pseudoseptic knee), in patients receiving Synvisc have been reported. One such patient developed antibodies to chicken proteins and hylan, suggesting an immunologic basis for the severe acute inflammatory reaction. Data from an animal study support a possible immunogenic difference between Synvisc and Hyalgan. CONCLUSIONS AND RELEVANCE: Overall, HA therapy is a safe treatment for OA knee pain, although there may be interproduct variability in safety profiles.