An international survey of current management practices for polymyalgia rheumatica by general practitioners and rheumatologists.

OBJECTIVES: To explore current management practices for PMR by general practitioners (GPs) and rheumatologists including implications for clinical trial recruitment. METHODS: An English language questionnaire was constructed by a working group of rheumatologists and GPs from six countries. The questionnaire focused on: 1: Respondent characteristics; 2: Referral practices; 3: Treatment with glucocorticoids; 4: Diagnostics; 5: Comorbidities; and 6: Barriers to research. The questionnaire was distributed to rheumatologists and GPs worldwide via members of the International PMR/Giant Cell Arteritis Study Group. RESULTS: In total, 394 GPs and 937 rheumatologists responded to the survey. GPs referred a median of 25% of their suspected PMR patients for diagnosis and 50% of these were returned to their GP for management. In general, 39% of rheumatologists evaluated patients with suspected PMR >2 weeks after referral, and a median of 50% of patients had started prednisolone before rheumatologist evaluation. Direct comparison of initial treatment showed that the percentage prescribing >25 mg prednisolone daily for patients was 30% for GPs and 12% for rheumatologists. Diagnostic imaging was rarely used. More than half (56%) of rheumatologists experienced difficulties recruiting people with PMR to clinical trials. CONCLUSION: This large international survey indicates that a large proportion of people with PMR are not referred for diagnosis, and that the proportion of treatment-naive patients declined with increasing time from referral to assessment. Strategies are needed to change referral and management of people with PMR, to improve clinical practice and facilitate recruitment to clinical trials.

The Clinical Impact of Seropositivity on Treatment Response in Patients with Rheumatoid Arthritis Treated with Etanercept: A Real-World Iraqi Experience.

Purpose: To assess the clinical impact of rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (ACPA)'s seropositivity on treatment response in patients with rheumatoid arthritis (RA) treated with etanercept. Patients and Methods: A retrospective analysis of patients with RA registered in Baghdad Teaching Hospital Registry from May 2012 to August 2019 was conducted. Patients aged ≥18 years, meeting the ACR/EULAR 2010 criteria for RA, being treated with etanercept, and followed up at ≥1 year after etanercept initiation were included; patients who received any other biologics for RA were excluded. Patients were classified as seropositive (RF- and ACPA-positive), seronegative (RF- and ACPA-negative), RF-positive, RF-negative, ACPA-positive, and ACPA-negative. The primary outcomes included Clinical Disease Activity Index (CDAI) and Disease Activity Score 28 (DAS28) which were measured at one year after treatment initiation. Results: At baseline, a total of 1318 (88.3%) patients were seropositive; 1122 (75.2%) and 1054 (70.6%) patients were RF- and ACPA-positive, respectively. Baseline mean CDAI scores were significantly (P = 0.001) higher among seropositive patients compared with seronegative patients. The baseline mean DAS28 score was also significantly higher in ACPA-positive group compared with the ACPA-negative group (P = 0.021). At baseline, the number of patients who had high CDAI scores was significantly higher among the seropositive, RF-positive, and ACPA-positive groups (P = 0.001, P = 0.001, and P = 0.002, respectively). After one year of treatment with etanercept, among seropositive versus seronegative and ACPA-positive versus ACPA-negative groups, there was a significant improvement in terms of the mean CDAI score (P = 0.004 and P = 0.017, respectively) and CDAI response (P = 0.011 and P = 0.048, respectively). At one year, the proportion of patients among the seropositive versus seronegative group who reached remission were 566 (42.9%) versus 78 (44.6%) and 642 (47.3%) versus 83 (47.4%), for CDAI and DAS28 response, respectively. Conclusion: The results imply that seropositivity and ACPA-positivity may influence the treatment response in patients with RA, who were treated with etanercept.

Clinical Outcomes in Iraqi Patients with Rheumatoid Arthritis Following Earlier or Later Treatment with Etanercept.

PURPOSE: The development of evidence-based guidelines on early pharmacotherapeutic treatment of rheumatoid arthritis (RA) could be useful in Middle Eastern nations striving to improve outcomes in patients with this chronic, debilitating disease. Evidence obtained from local populations should inform such guidelines and therefore our aim was to use real-world data to evaluate the clinical responses of Iraqi patients with RA who received earlier or later treatment with the TNF inhibitor etanercept. PATIENTS AND METHODS: Data from patients registered in the Iraq National Center of Rheumatology database from May 2012 to December 2018, inclusive, were analyzed retrospectively. Inclusion criteria were age ≥18 years, meeting the ACR/EULAR 2010 criteria for RA, referral for etanercept treatment, and ≥1 year of follow-up after etanercept initiation. Patients were excluded if they had received another biologic for RA. Included patients were categorized according to two separate stratifications: whether duration of RA symptoms prior to etanercept initiation was ≤10 or >10 years (10 years represented the mean duration for the entire analysis population); and according to whether duration of RA symptoms prior to etanercept initiation was ≤1, >1 to ≤4, >4 to ≤10, >10 to ≤20, or >20 years. The evaluated outcomes were mean change from baseline in Clinical Disease Activity Index (CDAI) and 28-joint Disease Activity Score (DAS28) after 1 year of etanercept treatment. RESULTS: A total of 979 patients were included. CDAI and DAS28 were significantly reduced (p<0.001 for both) after 1 year of etanercept treatment irrespective of whether duration of RA symptoms prior to treatment was ≤10 or >10 years. Patients with RA symptoms for ≤1 year prior to etanercept initiation showed a significant reduction in CDAI after 1 year of treatment (p=0.01). CONCLUSION: Iraqi patients with RA who received earlier treatment with etanercept had superior outcomes compared with those who received later treatment.

Review of biologics, biosimilars, and intended copies in rheumatology, and current practice in Iraq.

Biologic therapies are an important option in the treatment of patients with rheumatic disease. As the development of potential biosimilars increases, many countries are following the guidelines developed by the WHO, European Medicines Agency, or US Food and Drug Administration to create country-specific regulations for the review and approval of these products. Iraq does not yet have such regulations, and this presents a potential safety concern for patients. The analytical, nonclinical, and clinical data requirements for approval of a potential biosimilar are specific and scientifically rigorous. In some countries, products are available that have not met the stringent criteria for biosimilars; they are usually referred to as "intended copies". Frequently, the available data are not sufficient to demonstrate that they are similar in efficacy and safety to the reference product. Thus, safety issues may arise once the product is in use, as was the case with Kikuzubam, an intended copy of rituximab that was withdrawn from the market in Mexico following reports of severe adverse reactions. It is important to implement scientific, evidence-based guidelines for the review, approval, therapeutic use, and monitoring of biosimilars, and to provide training on this topic to healthcare professionals and patients. In this review, we discuss issues related to the use and regulation of biosimilars, and the differences between biosimilars and intended copies. We also provide suggestions for including biosimilars as a treatment option in Iraq.

Anti-tumor necrosis factor biosimilars and intended copies in rheumatology: Perspective from the Asia Pacific region.

Although anti-tumor necrosis factor (TNF) agents have greatly improved the management of rheumatic diseases, their cost limits access to many patients throughout the world. As a result, patients and clinicians have turned to biosimilars to provide similar efficacy at a lower cost. Many of the regulatory guidelines in the Asia Pacific region are largely based on those of the European Medicines Agency and the World Health Organization; however, there are variations between countries. Additionally, in some countries, intended copies are available that were approved prior to the development of guidelines and have not fulfilled the requirements of a biosimilar. We review the various regulatory requirements for biosimilars in the Asia Pacific region, the anti-TNF biosimilars and intended copies approved in the region, and whether clinical data are available for these agents. We discuss concerns about the need for additional regulations and education, and we provide recommendations for a multidisciplinary pharmacovigilance approach that closely monitors the safety of biosimilar use.

Biosimilars in rheumatology: recommendations for regulation and use in Middle Eastern countries.

The increasing availability of biosimilar medicines in Middle Eastern regions may provide an opportunity to increase the number of rheumatology patients who have access to traditionally more expensive biologic medicines. However, as well as a lack of real-world data on the use of biosimilar medicines in practice, the availability of intended copies in the region may undermine physician confidence in prescribing legitimate biosimilar medicines. There is a need for regional recommendations for healthcare professionals to ensure that biosimilar drugs can be used safely. Therefore, a literature search was performed with the aim of providing important recommendations for the regulation and use of biosimilar medicines in the Middle East from key opinion leaders in rheumatology from the region. These recommendations focus on improving the availability of relevant real-world data, ensuring that physicians are aware of the difference between intended copies and true biosimilars and ensuring that physicians are responsible for making any prescribing and switching decisions.