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.

The Prevalence of Non-radiographic Axial Spondyloarthritis Among Patients with Inflammatory Back Pain from Northwest and South Africa: Data from a Noninterventional, Cross-Sectional Study.

INTRODUCTION: Information is limited on the prevalence and clinical characteristics of nonradiographic axial spondyloarthritis (nr-axSpA) among patients with inflammatory back pain (IBP) in African countries. A global study estimated the prevalence of nr-axSpA among patients with IBP from 19 countries in Latin America, Europe, Asia, and Africa. This post hoc subset analysis focused on estimating prevalence of nr-axSpA and clinical characteristics among patients with IBP from Northwest Africa (Morocco and Algeria) and South Africa. METHODS: Patients from Northwest Africa and South Africa diagnosed with nr-axSpA according to protocol completed patient-reported outcome measures to assess disease activity and functional limitations, including Ankylosing Spondylitis Disease Activity Score (ASDAS). RESULTS: Of the 206 patients with IBP from Africa (n = 168, Northwest Africa and n = 38, South Africa), 33 (16.0%) were diagnosed with nr-axSpA (n = 26, Northwest Africa and n = 7, South Africa), corresponding to prevalence rates of 15.5% and 18.4%, respectively. Disease activity per region, measured as mean ASDAS, was 2.4 ± 1.4 and 2.4 ± 0.9, respectively, based on erythrocyte sedimentation rate and 2.4 ± 1.3 and 2.7 ± 0.7 based on C-reactive protein. CONCLUSIONS: Although the number of patients available for the analysis was low, it appears that the prevalence of nr-axSpA among patients with IBP is similar between Northwest and South Africa, and the disease burden is substantial. Limited access to magnetic resonance imaging may hinder early detection in these areas, thereby affecting the assessment of prevalence. FUNDING: Pfizer.

Maintenance of Remission with Etanercept-DMARD Combination Therapy Compared with DMARDs Alone in African and Middle Eastern Patients with Active Rheumatoid Arthritis.

INTRODUCTION: To compare etanercept (ETN) and placebo (PBO) for maintaining low disease activity (LDA) achieved with ETN in patients with rheumatoid arthritis (RA) from Africa and the Middle East. METHODS: In this subset analysis of the Treat-to-Target trial (ClinicalTrials.gov identifier NCT01981473), 53 adult patients with moderate-to-severe RA nonresponsive to methotrexate were treated with 50 mg ETN/week for 24 weeks (Period 1). Patients achieving LDA were randomized to continue ETN treatment or switched to PBO for an additional 28 weeks (Period 2). The proportion of patients maintaining LDA or remission in each arm at the end of Period 2 was determined. Additional efficacy and patient-reported outcomes (PROs) were also evaluated. RESULTS: During Period 1, 51 patients achieved LDA according to the disease activity score-28 joints-erythrocyte sedimentation rate (DAS28-ESR LDA) and 30 achieved remission. At week 52, nine of 22 and eight of 29 in the ETN and PBO groups, respectively, remained in DAS28-ESR LDA without experiencing a flare. Additionally, six of 14 and five of 16 in the ETN and PBO groups, respectively, remained in remission. Among patients experiencing a flare during Period 2, 13 of 22 and 21 of 29 received ETN or PBO, respectively. The median time to flare was 193 and 87 days in the ETN and PBO groups, respectively. At week 52, consistently more patients in the ETN group than in the PBO group achieved predetermined efficacy and PRO endpoints. CONCLUSIONS: These data suggest continuing ETN maintenance therapy is beneficial to patients after they have achieved their treatment target. However, this subset analysis is limited by the small patient population and must be interpreted with caution. FUNDING: Pfizer. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT0198147.

Experience and challenges for biologic use in the treatment of moderate-to-severe psoriasis in Africa and the Middle East region.

The incidence of psoriasis in Africa and the Middle East (AfME) is high as in other regions and represents a significant problem for both dermatologists and patients. Psoriasis co-morbidities such as obesity, cardiovascular disease and psoriatic arthritis (PsA) are also particularly common in these regions and may be under-recognized and under-treated. Despite this, regional guidelines to aid physicians on the appropriate use of biologic agents in their clinical practice are limited. A group of expert dermatologists from across the AfME region were surveyed to help establish best practice across the region, alongside supporting data from the literature. Although biologics have significantly improved patient outcomes since their introduction, the results of this survey identified several unmet needs, including the lack of consensus regarding their use in clinical practice. Discrepancy also exists among AfME physicians concerning the clinical relevance of immunogenicity to biologics, despite increasing data across inflammatory diseases. Significant treatment and management of challenges for psoriasis patients remain, and a move towards individualized, tailored care may help to address these issues. The development of specific local guidelines for the treatment of both psoriasis and PsA could also be a step towards understanding the distinct patient profiles in these regions.

The prevalence and clinical characteristics of nonradiographic axial spondyloarthritis among patients with inflammatory back pain in rheumatology practices: a multinational, multicenter study.

BACKGROUND: Patients with ankylosing spondylitis (AS), who by definition have radiographic sacroiliitis, typically experience symptoms for a decade or more before being diagnosed. Yet, even patients without radiographic sacroiliitis (i.e., nonradiographic axial spondyloarthritis [nr-axSpA]) report a significant disease burden. The primary objective of this study was to estimate the prevalence and clinical characteristics of nr-axSpA among patients with inflammatory back pain (IBP) in rheumatology clinics in a number of countries across the world. A secondary objective was to estimate the prevalence of IBP among patients with chronic low back pain (CLBP). METHODS: Data were collected from 51 rheumatology outpatient clinics in 19 countries in Latin America, Africa, Europe, and Asia. As consecutive patients with CLBP (N = 2517) were seen by physicians at the sites, their clinical histories were evaluated to determine whether they met the new Assessment of SpondyloArthritis international Society criteria for IBP. For those who did, their available clinical history (e.g., family history, C-reactive protein [CRP] levels) was documented in a case report form to establish whether they met criteria for nr-axSpA, AS, or other IBP. Patients diagnosed with nr-axSpA or AS completed patient-reported outcome measures to assess disease activity and functional limitations. RESULTS: A total of 2517 patients with CLBP were identified across all sites. Of these, 974 (38.70 %) fulfilled the criteria for IBP. Among IBP patients, 29.10 % met criteria for nr-axSpA, and 53.72 % met criteria for AS. The prevalence of nr-axSpA varied significantly by region (p < 0.05), with the highest prevalence reported in Asia (36.46 %) and the lowest reported in Africa (16.02 %). Patients with nr-axSpA reported mean ± SD Ankylosing Spondylitis Disease Activity Scores based on erythrocyte sedimentation rate and CRP of 2.62 ± 1.17 and 2.52 ± 1.21, respectively, indicating high levels of disease activity (patients with AS reported corresponding scores of 2.97 ± 1.13 and 2.93 ± 1.18). Similarly, the overall Bath Ankylosing Spondylitis Disease Activity Index score of 4.03 ± 2.23 for patients with nr-axSpA (4.56 ± 2.17 for patients with AS) suggested suboptimal disease control. CONCLUSIONS: These results suggest that, in the centers that participated in the study, 29 % of patients with IBP met the criteria for nr-axSpA and 39 % of patients with CLBP had IBP. The disease burden in nr-axSpA is substantial and similar to that of AS, with both groups of patients experiencing inadequate disease control. These findings suggest the need for early detection of nr-axSpA and initiation of available treatment options to slow disease progression and improve patient well-being.

Assessment of clinical efficacy and safety in a randomized double-blind study of etanercept and sulfasalazine in patients with ankylosing spondylitis from Eastern/Central Europe, Latin America, and Asia.

Despite the demonstrated efficacy of etanercept for the treatment of ankylosing spondylitis (AS), sulfasalazine is often prescribed, especially in countries with limited access to biologic agents. The objective of this subset analysis of the ASCEND trial was to compare the efficacy of etanercept and sulfasalazine in treating patients with AS from Asia, Eastern/Central Europe, and Latin America. A total of 287 patients, 190 receiving etanercept 50 mg once weekly and 97 receiving sulfasalazine 3 g daily, from eight countries were included in this subset analysis. Differences in disease activity and patient-reported outcomes assessing health-related quality-of-life (HRQoL) parameters in response to treatment were analyzed using the Cochran-Mantel-Haenszel test for categorical efficacy endpoints and analysis of covariance model for continuous variables. At week 16, a significantly greater proportion of patients receiving etanercept achieved ASAS20 (79.0 %) compared with patients receiving sulfasalazine (61.9 %; p = 0.002). At week 16, treatment with etanercept also resulted in significantly better responses than sulfasalazine for ASAS40 (64.7 vs. 35.1 %; p < 0.001), ASAS5/6 (48.1 vs. 26.3 %; p < 0.001), proportion of patients achieving 50 % response in Bath AS Disease Activity Index (65.8 vs. 42.3 %; p < 0.001), partial remission (35.3 vs. 17.5 %; p = 0.002), and all HRQoL parameters. Both treatments were well tolerated. Etanercept was significantly more effective than sulfasalazine in the treatment of patients with AS from Asia, Central/Eastern Europe, and Latin America.

Challenges of diagnosis and management of axial spondyloarthritis in North Africa and the Middle East: An expert consensus.

Axial spondyloarthritis (SpA) is a spectrum of inflammatory disease with stages characterized by both nonradiographic and radiographic sacroiliitis. Nonradiographic axial SpA is associated with health-related quality-of-life impairment and may progress to ankylosing spondylitis. Axial SpA has a low prevalence in some countries in North Africa and the Middle East, and pooling of data and resources is needed to increase understanding of the regional picture. Early diagnosis and effective treatment are required to reduce disease burden and prevent progression. Anti-TNF therapy is recommended for patients with persistently high disease activity despite conventional treatment, and has been shown to be effective in patients without radiographic damage. Diagnostic delays can be an obstacle to early treatment and appropriate referral strategies are needed. In some countries, restricted access to magnetic resonance imaging and anti-TNF agents presents a challenge. In this article, a group of experts from North Africa and the Middle East evaluated the diagnosis and management of axial SpA with particular reference to this region.

Clinical Assessment and Management of Spondyloarthritides in the Middle East: A Multinational Investigation.

Data on spondyloarthritis (SpA) from the Middle East are sparse and the management of these diseases in this area of the world faces a number of challenges, including the relevant resources to enable early diagnosis and referral and sufficient funds to aid the most appropriate treatment strategy. The objective was to report on the characteristics, disease burden, and treatment of SpA in the Middle East region and to highlight where management strategies could be improved, with the overall aim of achieving better patient outcomes. This multicenter, observational, cross-sectional study collected demographic, clinical, laboratory, and treatment data on 169 consecutive SpA patients at four centers (Egypt, Kuwait, Qatar, and Saudi Arabia). The data collected presents the average time from symptom onset to diagnosis along with the presence of comorbidities in the region and comparisons between treatment with NSAIDs and biologics. In the absence of regional registries of SpA patients, the data presented here provide a rare snapshot of the characteristics, disease burden, and treatment of these patients, highlighting the management challenges in the region.