Anti‐tumor necrosis factor therapy: the Australian experience

Anti‐tumor necrosis factor (TNF) therapy for the management of rheumatic diseases has been reimbursed in Australia progressively per agent and disease indication since 2003. Initial projections of uptake were grossly overestimated. In this article the anti‐TNF experience in Australia is reviewed, including results of an eligibility study, Australian Rheumatology Association guidelines, anti‐TNF registry, and a report of adverse effects. These observations may assist APLAR countries currently coming to terms with anti‐TNF drug registration and funding.     

WHO‐ILAR‐COPCORD in the Asia‐Pacific: the past,present and future

The aim of the Community Oriented Program for Control of Rheumatic Disorders (COPCORD) is reduction of community burden of rheumatic disorders, particularly in developing communities. Stage I entails estimation of prevalence and incidence of musculoskeletal pain and rheumatic disorders. Stage II is dedicated to education of health workers, patients and the community. Stage III deals with identification of risk factors for common rheumatic disorders and development of strategies for their primary and secondary prevention. So far Stage I data have been reported from 15 countries in the Asia‐Pacific countries. The prevalence of musculoskeletal pain has varied from 11.6% to 45.4%. The commonest sites of pain were low back, knee, neck and shoulder. Commonest rheumatic disorders were osteoarthritis of knees, non‐specific low back pain and soft tissue rheumatism. A few scattered educational activities have been reported from Indonesia and India. Systematic case‐controlled or cohort studies aimed at finding out the risk factors for common rheumatic disorders were scanty. However, several associations were reported from cross‐sectional prevalence surveys. It is imperative that the COPCORD investigators in the Asia‐Pacific region focus on finding out the modifiable risk factors for rheumatic disorders with properly designed studies, develop preventive strategies on the basis of identified risk factors and carry out interventional studies to test the efficacy of the strategies with validated outcome instruments.     

Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti‐tumor necrosis factor treatment. Part 2: Management

Because anti‐tumor necrosis factor (anti‐TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti‐TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection and prevention of latent TB infection, and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti‐TNF treatment. Twenty‐three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web‐based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 2 of the statements comprised three parts: (3) management of latent TB in preparation for anti‐TNF therapy, (4) monitoring during anti‐TNF therapy, and (5) management of an active TB infection after anti‐TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti‐TNF treatment.     

Experience with anti‐tumor necrosis factor‐α therapy in India

Aims: To review the Indian experience with anti‐tumor necrosis factor (TNF)‐α therapy. Methods: ‘PubMed’ and ‘IndMED’ were searched for Indian studies on anti‐TNF‐α therapy. Data were compiled and analysed. Results: Data on infliximab from 176 patients from five different series were collated. One hundred and forty‐seven had ankylosing spondylitis (AS), nine had polyarticular juvenile idiopathic arthritis (JIA), 12 had rheumatoid arthritis (RA), six had undifferentiated spondyloarthropathy, one had inflammatory bowel disease‐related spondyloarthritis and one had psoriatic arthritis. Thus, 155/176. (88%) had spondyloarthropathy (SpA). No screening for latent tuberculosis was done in any of the studies. One series comprising 108 cases of AS, used 3 mg/kg infliximab infusions (instead of 5 mg/kg) at 8‐weekly intervals with omission of the 2‐week and 6‐week doses. All others with SpA (n = 47) followed the standard protocol: 171/176 patients had a significant improvement. Reactivation tuberculosis developed in 5/47 (10.6%) SpA patients treated with standard doses of infliximab. This amounted to 56 times increased risk compared to baseline (0.187%). None of the 129 patients treated with 3 mg/kg infusions of infliximab developed reactivation tuberculosis (AS ?108, RA ?12, JIA ?9). The lone study on etanercept showed good efficacy in 40 patients with RA. However, seven serious adverse events occurred. Conclusions: Infliximab showed expected efficacy in SpA, RA and JIA. Reactivation tuberculosis developed in 10.6% of the SpA group treated with standard regimen. Patients treated with lower doses of infliximab which included a large subgroup of SpA patients and those with RA or JIA did not develop tuberculosis.     

Understanding the complications of anti‐tumor necrosis factor therapy in East Asian patients with inflammatory bowel disease

Remarkable advances have been made in the treatment of inflammatory bowel disease since the introduction of anti‐tumor necrosis factor‐α agents, especially for patients who are refractory to or cannot tolerate conventional therapies. Currently, infliximab, adalimumab, and golimumab are available in the East Asian medical market, and these agents have been shown to be effective for inducing and maintaining long‐term remission of inflammatory bowel disease. Despite their clinical benefits, anti‐tumor necrosis factor therapy can also lead to increased vulnerability to infections, development of autoimmune diseases and malignancy, and decreased immunogenicity of vaccinations. Because infectious diseases, such as tuberculosis, hepatitis, and influenza, remain major health problems in East Asia, more cautious use of biologics is needed. To further improve treatment efficacy and safety, close monitoring of inflammation, regular surveillance for malignancy, and regularly scheduled vaccinations are needed. Treatment strategies for biologics should be customized to meet the needs of different patients.     

The infectious profiles of anti‐tumor necrosis factor agents in a Thai population: a retrospective study a the university‐based hospital

Aims: Anti‐tumour necrosis factor‐α (anti‐TNF) agents represented treatment advances in a number of rheumatologic diseases. However, adverse effects of anti‐TNF agents have been identified through both clinical trials and post‐marketing surveillance, especially an increased risk of serious infections. This study firstly described the infectious profiles of anti‐TNF agents in a Thai population. Methods: We retrospectively reviewed all infectious incidences from 100 consecutive medical records of patients who were treated with either etanercept or infliximab for any rheumatologic and non‐rheumatologic conditions. Results: Indications for anti TNF‐α agents were mainly rheumatoid arthritis (46%) and spondyloarthropathy (SpA) (41%). Seventy‐seven patients were treated with etanercept and 23 with infliximab. For those whose initial treatment was etanercept, there were two events of suspected active pulmonary tuberculosis (TB) and suspected hepatitis‐B virus (HBV) reactivation. Two out of 23 patients (8.7%) who were firstly treated with infliximab had herpes zoster skin infection. Incidence of overall infection before anti‐TNF treatment were significantly higher in patient who started with etanercept (0.065 vs. 0.019 cases per person‐years in etanercept and infliximab respectively, P < 0.0001). Incidence of overall infection post‐anti‐TNF treatment were 0.122 and 0.201 cases per person‐years in patients who started with etanercept and infliximab with no significant difference (P > 0.05). The overall infection rates were significantly increased after infliximab treatment (P < 0.0001). Conclusion: Even thought there were two new events of TB and HBV reactivation after etanercept treatment, incidence of overall infection seemed to be increased after infliximab treatment. The infectious screening and monitoring with high index of suspicion as well as the pre‐emptive treatment are still important whenever either etanercept or infliximab is started.     

Hepatitis B: overview of the burden of disease in the Asia‐Pacific region

Abstract: Hepatitis B virus (HBV) infection and its liver‐related complications are a substantial health concern in the Asia‐Pacific region. Over the last two decades, public health interventions and the implementation of universal vaccination programs have substantially reduced the incidence of HBV infections in many countries in this region. However, large proportions of individuals remain chronically infected and subject to an increased risk for serious sequelae, including cirrhosis, decompensated liver disease, and hepatocellular carcinoma. The management of HBV infection varies throughout the Asia‐Pacific region, with each country confronting different issues related to prevention, screening, and treatment. These issues include the availability of diagnostic testing and treatment, the cost of diagnosis and treatment, the availability of trained medical professionals and medical facilities, and disease awareness among primary care physicians and the public. This article reviews the epidemiology of HBV infection in the Asia‐Pacific region, explains factors influencing hepatitis B prevalence and prevention, and discusses barriers to prevention and treatment of chronic hepatitis B and its liver‐related complications.     

Challenges to and opportunities for the implementation of non‐invasive positive pressure ventilation in the Asia‐Pacific region

Non‐invasive positive pressure ventilation (NPPV) is undoubtedly one of the most significant advancements in mechanical ventilation technology in the past 30 years. With accumulating evidence from clinical studies and support from clinical guidelines, NPPV is now widely used in hospitals and increasingly prescribed for home therapy in the Asia‐Pacific region. However, in comparison with the developed Western countries, overall use of NPPV in the region is lagging behind. This study reviews this imbalance of NPPV use both in the acute and domiciliary settings in the Asia‐Pacific region. Important issues related to NPPV use are also discussed along with speculation around potential strategies that could promote wider implementation of NPPV in the region. We hope this review will stimulate interest in the clinical application and potential research avenues for NPPV in the Asia‐Pacific region, and promote education and staff training in the technique.     

Asian Organization for Crohn's and Colitis and Asian Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti‐tumor necrosis factor treatment. Part 1: Risk assessment

Because anti‐tumor necrosis factor (anti‐TNF) therapy has become increasingly popular in many Asian countries, the risk of developing active tuberculosis (TB) among anti‐TNF users may raise serious health problems in this region. Thus, the Asian Organization for Crohn's and Colitis and the Asian Pacific Association of Gastroenterology have developed a set of consensus statements about risk assessment, detection, and prevention of latent TB infection and management of active TB infection in patients with inflammatory bowel disease (IBD) receiving anti‐TNF treatment. Twenty‐three consensus statements were initially drafted and then discussed by the committee members. The quality of evidence and the strength of recommendations were assessed by using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Web‐based consensus voting was performed by 211 IBD specialists from nine Asian countries concerning each statement. A consensus statement was accepted if at least 75% of the participants agreed. Part 1 of the statements comprised two parts: (i) risk of TB infection during anti‐TNF therapy and (ii) screening for TB infection prior to commencing anti‐TNF therapy. These consensus statements will help clinicians optimize patient outcomes by reducing the morbidity and mortality related to TB infections in patients with IBD receiving anti‐TNF treatment.     

Non‐tumor necrosis factor biological therapies for rheumatoid arthritis

The emergence and use of the biological agents is one of the major recent advances in the treatment of rheumatoid arthritis. Although the tumour necrosis factor alpha (TNF‐α) inhibitors are superior to conventional disease‐modifying antirheumatic drugs (DMARDs) in terms of efficacy, certain patients may still be unresponsive or intolerant to them. Moreover, infection such as tuberculosis and the possibility of long‐term adverse effects such as malignancies are major concerns of the anti‐TNF‐α agents. Thus, newer and, hopefully, more effective but less toxic biological agents have to be developed as alternative therapies. This article reviews the preliminary clinical data on several non‐TNF‐α biological agents in the treatment of rheumatoid arthritis.     

Extended indications for anti‐tumor necrosis factor‐α therapy

Tumour necrosis factor‐α is a pleiotropic cytokine which has a broad range of actions in inflammation, infection and immunity. TNF‐α is supposed to play a crucial role in the pathogenesis of various autoimmune diseases. TNF‐α blocking agents have been demonstrated to be highly effective in the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and juvenile rheumatoid arthritis. TNF‐α inhibitors also have been tried with other rheumatic diseases and have emerged as promising treatments. We here review the current evidences of effectiveness of the anti‐TNF‐α therapy in various autoimmune diseases.     

Higher-than-optimal body mass index and diabetes mortality in the Asia Pacific region

Aims

To estimate the population attributable fraction (PAF) of elevated body mass index (BMI) for diabetes mortality by country, sex and age group, for the Western Pacific and South-East Asia regions.

Methods

Published data on nationally representative mean BMI (since year 2000) and age-specific hazard ratios for death due to diabetes for a unit increase in BMI were used to calculate PAFs using the methodology of the WHO Global Burden of Disease project, taking a BMI of 21 kg/m² as the ideal.

Results

Data were available for 15 countries in the Western Pacific and South East Asia regions. This included data from 330,374 individuals. Age-standardized male PAFs ranged from 11% for India to 98% for American Samoa. Age-standardized female PAFs ranged from 9% in India to 95% in American Samoa. For males, several countries had PAFs at or below 30% - these were India, Indonesia and Japan; whereas, India and Indonesia were the only two countries with PAFs below approximately 30% for females.

Conclusion

Although this study is not a trial and thus not able to definitively state the proportions of diabetes deaths that could be averted by reducing mean BMI, this paper demonstrates that theoretically between 9% and 98% of deaths from diabetes could be prevented by tackling obesity in the Asia Pacific region. Preventing these deaths is likely to have an enormous positive social and economic impact, particularly in this region consisting of many low and middle-income countries.