Rheumatology Advance Access originally published online on October 12, 2009
Rheumatology 2009 48(11):1335-1336; doi:10.1093/rheumatology/kep334
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Editorial |
Registries in rheumatological and musculoskeletal conditions—call for papers
1UCL Division of Medicine, Centre for Rheumatology, University College London, London, UK, 2University of Texas Southwestern Medical Center, Metroplex Clinical Research Center, Dallas, TX, USA and 3Department of Rheumatology and Clinical Immunology, Justus-Liebig University Giessen, Kerckhoff-Clinic, Bad Nauheim, Germany.
Correspondence to: David Isenberg, UCL Division of Medicine, Centre for Rheumatology, University College London, Windeyer Building, 46 Cleveland Street, London W1T 4JF, UK. E-mail: d.isenberg{at}ucl.ac.uk
The outlook for patients with various inflammatory arthropathies, notably RA, PsA and AS, has been altered substantially in the past decade by the introduction of biologic agents, in particular those which block TNF-
and also by agents that either block co-stimulation or affect CD20 B cells. Although double-blind control trials involving thousands of patients have demonstrated the effectiveness of these drugs, such as etancercept [1], infliximab [2], adalimumab [3] and newer drugs such as certolizumab golimumab, abatacept and rituximab, real life experience of using these drugs is essential if we are to capture accurately the long-term benefits and side effects. By consent, the introduction of biologic registries of patients treated with biologics has provided a major advance in our ability to determine, evaluate and utilize these real life experiences. Many of these local, national and international registries have become a key tool in efforts to ascertain both the medium term (2–5 years) and, increasingly, the long-term outcome (>5 years) for patients, in whom the effects of pro-inflammatory cytokines and cells are being inhibited or even completely blocked.
The use of these registries, especially for patients with RA, has, for example, demonstrated that TNF- inhibitors are associated with an increased rate of infection [4], which is particularly evident in the first 90 days after the initiation of therapy, especially in the lower respiratory tract [5]. Reactivation of tuberculosis is a serious potential problem of anti-TNF- therapy [6], but this serious and hitherto unknown problem can be overcome by a pre-therapeutic tuberculosis skin screening and a chest X-ray, which will detect most (although not all) cases of latent tuberculosis [7]. More encouragingly, TNF- blockade has, so far, shown no overall increase in cancer risk [8] and appears to reduce cardiovascular morbidity and mortality [9], especially when the clinical symptoms respond to treatment.
Establishment of biologic registers, their design and how they acquire data are challenging and expensive issues. Registers overtly supported by pharmacological companies are liable to a criticism of company bias, yet few government departments are willing to contemplate supporting these valuable research tools.
In the next decade(s), rheumatologists, and those who fund clinical care for patients with musculoskeletal conditions, will face even bigger challenges. Monoclonal antibodies (and other biological approaches) to a variety of key cytokines, cells and molecules are now, or will shortly be, available. Although the key questions of drug effectiveness, side effects and costs will ultimately determine the fate of these new approaches, important subsidiary questions will need to be answered. For example, how are rheumatologists to make decisions about the optimal management of patients with RA, PsA and AS? In addition, it seems that biologic agents may well prove very helpful for patients with SLE, vasculitis and Sjögren's syndrome, but owing to the variability of these entities, the challenges of proving the efficacy and ensuring the relative safety of biologic drugs are bigger than for a standard RA setting. Among other critical questions that will need to be addressed are whether we can identify patients who are likely to require biologic agents sooner rather than later; if there is an optimal sequence of biologic agents to be tried in individual conditions; to what extent biomarkers may help to guide our use of individual biologic agents and what the long-term safety sequelae of biologic agents really are.
We, the editor and editorial staff at Rheumatology, feel that it would be timely to try and address these vital questions and would like to issue a call for papers dedicated to a whole issue of the Journal to the role of biologic registers in January 2011. We thus invite original and review articles related to a variety of facets of biologic registers. These topics will include problems and solutions of registry design; biometric and logistic pitfalls and escape strategies; how should registry best be funded; the establishment of multi-national registers focusing on a single rare disease or a group of diseases; how national registries should best capture treatment, treatment defects and failures—including long-term side effects and how registers might best work together effectively to increase the pool of knowledge. Comparisons among registers exploring their respective strengths and weaknesses will also be most welcome.
We invite contributors to submit suitable manuscripts by 1 April 2010. Please mention ‘Theme issue 2010’ in your covering letter as well as the title of your manuscript. All manuscripts should be submitted online via http://mc.manuscriptcentral.com/rheumatology. For more details about the call for the papers, please visit http://www.oxfordjournals.org/our_journals/brheum/callforpapers_registries.html.
Disclosure statement: U.M.-L. has received honoraria from Abbott, Essex, UCB, Wyeth, Merck, Actellion, MSD, Medac, BMS and Roche/Chugai. D. I. has consulted for Roche, Merck-Serono, Teva, Bristol Myers Squibb and Celltech. He does not accept personal remuneration from these companies and the honoraria are paid to a local arthritis charity. The other author has declared no conflicts of interest.
References
- Van der Heijde D, Klareskog L, Rodriguez-Valverde V, et al. Comparison of etanercept and methotrexate, alone and combined in the treatment of rheumatic arthritis. Arthritis Rheum (2006) 54:1063–74.[CrossRef][Web of Science][Medline]
- Maini R, St Clair EW, Breedveld F, et al, and the ATTRACT Study Group. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. Lancet (1999) 354:1932–9.[CrossRef][Web of Science][Medline]
- Weinblatt ME, Keystone EC, Furst DE, et al. Adalimumab, a fully human anti-tumour necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum (2003) 48:35–45.[CrossRef][Web of Science][Medline]
- Dixon WG, Symmons DC, Lunt M, et al. Serious infection following anti tumour necrosis factor alpha therapy in patients with rheumatoid arthritis: lessons from interpreting data from observational studies. Arthritis Rheum (2007) 56:2896–904.[CrossRef][Web of Science][Medline]
- Dixon WG, Watson K, Lunt M, et al. Rates of serious infection, including site-specific and bacterial intra-cellular infection, in rheumatoid arthritis patients receiving anti-tumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum (2006) 54:2368–76.[CrossRef][Web of Science][Medline]
- Keane J, Gershon S, Wise RP, et al. Tuberculosis associated with infliximab, a tumour necrosis factor alpha neutralizing agent. N Engl J Med (2001) 345:1098–104.
[Abstract/Free Full Text] - Tubach F, Salmon D, Ravaud P, et al, for the RATIO group. Definitive results of the national French prospective RATIO 3-year observatory on tuberculosis in patients treated with TNF blockers: the risk persists but depends on the drug. Arthritis Rheum (2007) 56:5158.
- Askling J, for the ARTIS Study Group. No increase in overall risk for cancer in RA treated with TNF-antagonists but risks for certain types may be elevated. Ann Rheum Dis (2007) 66(Suppl. ii):54.
- Dixon WG, Symmons DPM. What effects might anti-TNF treatment might be expected to have on cardiovascular morbidity and mortality in rheumatoid arthritis? A review of the role of TNF in cardiovascular pathophysiology. Am Rheum Dis (2007) 66:1132–6.[CrossRef]
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