Towards improved treatment of undifferentiated and rheumatoid arthritis
Visser, K.
Citation
Visser, K. (2011, December 8). Towards improved treatment of undifferentiated and rheumatoid arthritis. Retrieved from https://hdl.handle.net/1887/18197
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General Introduction
1
10 | Chapter 1
Rheumatoid arthritis
Rheumatoid arthritis (RA) is a systemic auto-immune inflammatory joint disease with the potential of having a chronic destructive course.1The prevalence of RA is approxima- tely 0.5-1 percent in European and North American countries, with an incidence of 20- 50/100.000 new cases per year. Women are affected two to three times more often than men.2Multiple genes and environmental factors play a role in the pathogenesis, which is still being unraveled.3 RA is characterized by inflammation of synovial joints, typically including the small joints of the hands and feet, leading to symptoms of pain, swelling and restriction of movement. Systemic symptoms include morning stiffness, malaise, anorexia and weight loss, and fever.4 Without effective and timely antirheu- matic treatment, chronic inflammation leads to synovial hyperplasia, cartilage and bone degradation, resulting in progressive joint destruction, which manifests as the typical radiographic features of bone erosions and joint space narrowing. Disease acti- vity, mostly in the early stage of the disease, and joint damage, more pronounced later in the disease, both result in functional impairment and contribute to the reduced qua- lity of life and work loss experienced by patients with RA.5-7After prolonged inflamma- tion, extraarticular manifestations such as rheumatoid nodules, rheumatoid vasculitis, pulmonary and ocular inflammation, and in particular cardiovascular disease may even result in increased mortality.8-10Thus, the clinical, social and economic burden that po- ses RA underscores the importance of effective therapeutic intervention. However, in individual patients the disease course is variable and ranges from mild non-destructive to rapidly progressive poor prognosis RA.11
Diagnosis
Although earlier descriptions of RA date back to 1800, Garrod was the first to name the disease ‘rheumatoid arthritis’ in 1850.12,13 Only a hundred years later, the American Col- lege of Rheumatology (ACR) proposed the first classification criteria, in order to distin- guish RA from other types of joint diseases.14 In 1987 the criteria were revised (table 1).15 The 1987 criteria have served well as inclusion criteria to select homogeneous patient groups for clinical trials, but they have been criticized for the lack of diagnostic value.
Since the presence of nodules, erosions and chronicity are hallmarks of more advanced disease, the sensitivity and specificity of the 1987 criteria for early diagnosis of RA are poor.16 In addition, the presence of rheumatoid factor is not unique for RA and more specific serological markers have been identified, including the widely studied antibo- dies against citrullinated proteins (ACPA).17Incorporation of ACPA into the criteria has been shown to improve the sensitivity for recent-onset RA.18Most importantly, anti- rheumatic treatment should preferably be started before the hallmarks of RA have de- veloped, in order to prevent patients from reaching the chronic destructive state charac- terized by the 1987 criteria. Therefore, it is crucial to identify RA in a much earlier stage.
Table 1. American College of Rheumatology classification criteria for probable rheumatoid arthritis (1958) and rheumatoid arthritis (1987).
1958 ACR criteria for probable RA 1987 ACR criteria for RA
1. Morning stiffness 1. Morning stiffness lasting at least 1 hour 2. Swelling (soft-tissue or fluid) of a joint 2. Swelling (soft-tissue or fluid) of at least
three joint areas
3. Swelling of another joint 3. Swelling of a hand joint area (wrist, MCP, PIP)
4. Pain on motion or tenderness in a joint 4. Symmetrical joint swelling 5. Symmetrical joint swelling 5. Subcutaneous nodules 6. Subcutaneous nodules 6. Positive rheumatoid factor
7. Positive rheumatoid factor 7. Typical radiographic changes on hand TT and wrist radiographs (erosions or juxta-articular osteoporosis) 8. Typical radiographic changes (erosions TT
or unequivocal bony decalcification) 9. Mucin clot from synovial fluid 10. Characteristic histological synovial
changes
11. Characteristic histological nodule changes
* Criteria 1-5 present for at least 6 weeks * Criteria 1-4 present for at least 6 weeks
* Probable RA = 3/11 criteria met * RA = at least 4/7 criteria met MCP=metacarpal phalangeal joint; PIP= proximal interphalangeal joint
Undifferentiated arthritis
Patients with RA may present with typically distributed inflammatory polyarthritis, but can also have mono- or oligoarthritis, which does not (yet) fulfill criteria for any rheu- matologic disorder. If no certain diagnosis can be made, this form of arthritis is called unclassified or undifferentiated arthritis (UA).19 UA represents a variety of disorders, some self-limiting and prone to go into spontaneous remission, others potentially chro- nic and damaging. Follow-up data of various Early Arthritis Cohorts, set up to promote
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early detection and treatment of rheumatic disorders, have shown that up to 50% of UA patients have self-limiting disease, whereas 17-32% (depending on the definition of UA) eventually progress to a syndrome that fulfills the 1987 ACR classification criteria for RA (table 1).20-22The prognosis of those patients who present with UA but progress to RA within one year is similar to that of patients who present with RA at baseline.23 Thus, a subset of UA patients is actually in an early stage of RA.
Since it has become clear that starting treatment with disease-modifying antirheuma- tic drugs (DMARDs) earlier leads to improved outcomes for patients with RA, starting antirheumatic therapy already in the UA phase might result in even more sustained benefits and potentially even a chance for cure.24-26 This has been called the ‘window of opportunity’ hypothesis, pointing towards a restricted timeframe where therapeutic intervention might permanently alter the disease course.27To avoid inappropriate treat- ment of patients who will go into spontaneous remission or have other diagnoses, there is a need to identify which UA patients will go on to have a chronic destructive disease course. Several prediction models have been developed for this purpose, but prediction is not yet accurate enough for all UA patients.28,29 Since no classification cri- teria for UA exist, the studied patients with UA in part I of this thesis had to fulfill the 1958 criteria for probable RA (table 1), as a means of defining early inflammatory arthritis prone to become persistent.14
Anti-citrullinated protein antibodies
One of the most important and widely studied markers for early RA is the presence of antibodies against citrullinated proteins (ACPA) in the serum of patients with arthritis.
ACPA are measured with the anti-cyclic citrullinated peptides (anti-CCP) test, which has a comparable sensitivity (approximately 70%), but higher specificity (95% versus less than 90%) than reumatoid factor (RF), the traditional marker for RA.30Interestingly, ACPA can be found in serum years before the appearance of clinical symptoms and pre- dict the development from UA into RA.31-33 In established RA, ACPA are also associated with a higher rate of radiographic progression and worse disease outcome.34 Further- more, they are present in affected joints and have been shown to enhance arthritis in an experimental mouse model.35 All this evidence suggest an important role for ACPA in the pathogenesis of RA, but it is not yet clear whether ACPA are cause or result of the immunopathologic processes in the joint.36Although research has mainly focused on ACPA-positive disease, around fifty percent of UA patients (depending on the inclusion criteria) and one third of RA patients is ACPA-negative. ACPA-negative disease appears to confer a different genetic predisposition, different environmental risk factors and different clinical outcome compared to ACPA-positive disease. For example, long known risk factors for RA, the shared epitope allele for the HLA-DRB1 molecule and smoking, are associated with ACPA-positive, but not with ACPA-negative RA and histopathologi- cal features are also different. 37, 38This has led to the view that ACPA-positive and ACPA- negative RA are distinct disease entities, which still need to be further elucidated.
Disease-modifying antirheumatic drugs
The armamentarium of therapeutic agents for RA, known as disease-modifying anti- rheumatic drugs (DMARDs), has largely broadened in the past two decades. The num- ber of randomized comparative trials evaluating conventional drugs has dramatically grown and new biological drugs tackling specific molecular targets have been desig- ned, as a result of increased knowledge on pathofysiological pathways in RA.
Methotrexate
Methotrexate is regarded as the cornerstone of RA treatment. Since its first use in pa- tients with RA in the 1960s, the efficacy and toxicity profile of methotrexate (MTX) has been well established in randomized controlled trials (RCTs) in the early 1980s and in longitudinal cohort studies in the 1990s.39-42 MTX has shown higher retention rates compared with other DMARDs in long-term observational studies, demonstrating its favorable efficacy/toxicity ratio.43,44 In addition, MTX suppresses the progression of ra- diographic joint damage.45,46In high dosages, MTX as a folate antagonist acts anti-pro- liferative via blocking purine synthesis. However, in the dosages used in RA, 7.5-30 mg/
wk, MTX probably has immunosuppressive actions via various routes which are still being explored.47 There is large variability in how patients respond to MTX, both in terms of efficacy and toxicity. Only part of this variation can be explained with clinical markers, such as gender, baseline disease activity and RF status, but pharmacogenetic data might enhance the prediction of the response.48,49Multiple polymorphisms in genes encoding proteins in the MTX metabolic pathways have already been linked to either efficacy or toxicity.50
MTX is currently recommended by the European League Against Rheumatism (EULAR) as the first DMARD of choice in the treatment of RA and as the anchor drug to which other DMARDs can be combined and new drugs can be evaluated.51,52 Surprisingly, despite the widespread use and long-term experience, considerable variation still exists among rheumatologists in prescribing and managing MTX.53,54Only few countries have elaborated national guidelines for the use of MTX, and the existing ones often lack the level of detail required for specific clinical situations. Therefore, evidence and consensus based recommendations for the use of MTX in daily practice would be of great value.
Other conventional DMARDs
Since the 1920s, one of the oldest drugs used for the treatment of RA are injectable or oral gold salts. Despite the reasonable efficacy, the use of gold salts has declined since the emergence of more rapidly active and less toxic DMARDs such as MTX and sulpha- salazine.55-58Sulphasalazine was specifically synthesized for the treatment of RA in the 1940s, but was only generally accepted in the 1980s.59 It can be used as monotherapy or in combination with MTX or antimalarials, although the additional efficacy of some of these combinations remains controversial.60-64Antimalarials, including chloroquine and hydroxychloroquine have been used since the 1950s, but are generally regarded as less potent DMARDs. However, because of their favorable safety profile and possible syner- gistic effect together with MTX, they are often used in combination therapy.63-65Lefluno- mide was developed in the 1990s, has demonstrated comparable efficacy as MTX and
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sulphasalazine and thus is often used as an alternative to these drugs.45,66However, concerns have been raised over increased toxicity of leflunomide in combination with MTX.67,68
Corticosteroids
Corticosteroids have played a pivotal role and are still frequently used in the treatment of RA, since they rapidly alleviate clinical symptoms and also have a modifying effect on the progression of joint destruction.69-71 Prednisone appears to be a crucial component of effective combination therapies with other conventional DMARDs.69,72,65,73However, corticosteroid use has been limited by the fear for the side effects of prolonged use and higher dosages, both by patients and rheumatologists.74,75,76 It can be debated whether these concerns are also justified for lower dosed or short-term induction courses of prednisone, as recent safety data seem reassuring and biological actions of lower dosa- ges of corticosteroids appear considerably different.76,73,77Nevertheless, in the last de- cade, the use of systemic glucocorticoids has seen a revival and recommendations for use and further research have been developed.78
Biologicals
The advent of biologic agents in the 1990s has marked a new era of RA treatment, one with impressive improvements in the clinical and radiographic outcome of RA. Biologi- cals, so called because they are produced via molecular biology techniques, target spe- cific cells or cytokines in the pathofysiological pathways of RA. The first available agents were blockers of tumor necrosis factor (TNF), a proinflammatory cytokine discovered to play a central role in the inflammatory process.79Infliximab (chimeric anti-TNF) and eta- nercept (recombinant human soluble anti-TNF-receptor) were first registered, followed later by adalimumab (recombinant humanized anti-TNF). Anti-TNF rapidly and drama- tically reduces inflammation and can halt radiographic progression, even better when combined with MTX therapy, both in patients who had an inadequate response to prior DMARDs and in recent-onset DMARD-naive RA.80-86The efficacy of infliximab, etaner- cept and adalimumab seems comparable, but no head-to-head trials have yet been per- formed.87-89
The repertoire of biologic agents is still expanding. Two new TNF-blockers, certolizumab pegol and golimumab, have recently been approved.90 For patients with active RA who failed to respond to traditional DMARDs or anti-TNF, anakinra (interleukine-1 receptor antagonist), rituximab (B-cell depletor), abatacept (inhibitor of T-cell costimulatory pathways) and tocilizumab (interleukine-6 receptor antagonist) are now available.91-94 Despite the high efficacy of these drugs, concerns remain about the increased risk of infections, especially tuberculosis, possibly of malignancies and the considerable costs.
Therefore, in the Netherlands, the prescription of biologicals is restricted to patients who have failed on at least two conventional DMARDs including MTX. A current chal- lenge is to identify which patients are in need of earlier start of biologic therapy, and for which patients conventional DMARDs are a good initial choice, in order to maximize cost-efficiency and minimize overtreatment.
Treatment strategies
Strategies of RA treatment have also changed drastically in the past decades. Up until the 1980s, treatment followed the ‘pyramid approach’ in which the drugs considered least toxic such as analgesics and non-steroidal antiinflammatory drugs (NSAIDs) were prescribed first. ‘Second-line’ DMARDs were regarded more toxic and were only initia- ted after failure of the first-line drugs or in case of progressive erosive disease. However, once the toxicity profile of NSAIDs and DMARDs has been shown to be similar, and the debilitating outcome of RA patients was recognized, the more intensive ‘saw-tooth’
principle was introduced which advocated earlier, continuous and serial use of DMARDs.95-97
In the past decade, four important further changes have led to considerably improved treatment outcomes. First, early diagnosis and prompt initiation of DMARD therapy led to earlier suppression of disease activity with long-term impact.24-26,98 Second, DMARD combination therapies, especially those including corticosteroids, have proven superior without more toxicity than DMARD monotherapies.64 65, 99,100 Third, the advent of the targeted therapies, most importantly anti-TNF, which have shown to be highly effective in combination with MTX both in DMARD-naive patients and in patients who failed previous DMARD therapy.80,84-86,101Finally, so called ‘tight-control’ (frequent evaluations and adjustments of therapy with validated tools aiming at a pre-set goal of minimal disease activity), has been proven to result in better outcomes than ‘routine care’.102-105 As a result of these changes, sustained disease remission has become an achievable goal of RA treatment.106
The BeSt study
The BeSt (acronym for ‘Behandel Strategieën’) study has combined these therapeutic innovations, starting with early, tightly controlled treatment (via aiming at a low disease activity score) in four different treatment arms, including initial monotherapy (arms 1 and 2) and initial combination therapy with either prednisone (arm 3) or with the TNF-blocker infliximab (arm 4), in patients with recent-onset RA. This approach has resulted in a remarkable clinical improvement and reduction of radiological damage progression in the majority of patients.100 The observation that clinical remission could be achieved and, in part of the patients, could be maintained after tapering and discon- tinuation of all antirheumatic medication, illustrates the window of opportunity for changing the disease outcome, even in patients who had already progressed to full- blown RA.106 The next challenge is to increase the rate of drug-free remission induction, possibly by starting effective treatment earlier in the disease course, in patients with UA.
Outcome
The development of responsive and validated methods to measure outcome in RA has largely contributed to the advanced evaluation and use of antirheumatic drugs. Core set variables have been formulated by the Outcome Measures in Rheumatoid Arthritis Cli- nical Trials Committee (OMERACT) and ACR/EULAR collaborations and include disease activity, functional ability and joint damage assessment.107,108 Physician-based measures
16 | Chapter 1
include tender and swollen joint counts, assessing between 28 and 68 joints, according to various available scores.109-111 Laboratory measures closely reflecting inflammation in- clude acute phase reactants, such as the erythrocyte sedimentation rate (ESR) and C-re- active protein (CRP). Patients can self-report pain, global health, morning stiffness, disease activity and fatigue on a 100 mm visual analog scale (VAS).112
Disease activity
Several of these physician-based, patient-based and more direct inflammation markers have been combined into single measures to better describe the disease activity from different points of view. This has resulted in various indices of disease activity, of which the disease activity score (DAS) is one of the most frequently used.113 The DAS consists of the Ritchie articular index, a 44 swollen joint count, patient global health measured on a VAS, and the ESR. Effects of treatment can be measured in absolute values of disease activity measures or as relative changes. ACR response criteria have been formulated to define 20%, 50% or 70% improvement in the core set variables.114 EULAR response crite- ria define good, moderate or no treatment response using both absolute values and relative changes of the DAS.115
Functional ability
Physical function is one of the most traditional outcome measures in RA and is assessed via the Health Assessment Questionnaire (HAQ), a self-assessed questionnaire asking about the ability of a patient to perform regular daily activities.116,117 The HAQ grades functional disability on a scale of 0-3 and the minimally clinical important difference is approximately 0.22, but may be smaller in clinical practice.118,119It has been shown that the HAQ correlates well with disease activity and is a strong predictor for future disabi- lity and mortality.120,121
Radiographic progression
Plain radiographs of hands and feet still form the gold standard of assessing joint da- mage in RA. One of the most widely used methods is the Van der Heijde modified Sharp score (SHS), which quantifies joint space narrowing and erosions in 44 joint locations in hands and feet, with a maximum score of 448.122 The percentage of patients suffering progression above the level of measurement error can be calculated using the smallest detectable change (SDC) and individual data can be visualized in probability plots.123,124 The observation that radiographic damage and disease activity independently contri- bute to impaired physical function forms a rationale for steering at minimal disease ac- tivity and damage progression.125Whether these relationships also exist in UA is not known.
Remission
Clinical remission of disease is another important endpoint, for which ACR remission crite- ria have been proposed and have been linked to a DAS<1.6 as remission cut-off.126However, since these definitions allow for residual or subclinical inflammation, it can be argued that remission should be defined more strictly.127A task force is currently investigating a uni-
form definition of remission, also in order to increase homogeneity of trial reports.128 The ultimate goal of antirheumatic therapy would be complete absence of disease activity, which can be sustained after discontinuation of therapy, closely resembling resolution of the disease. This state of drug-free remission has been reported in a subset of patients, but it is not yet clear whether this is intrinsically limited to certain patients, or that we are able to influence this state with early intensive tightly controlled treatment.129,130
Methodology and statistics
In part I and III of this thesis, statistical models have been used to study associations between multiple explanatory or predictor variables (covariates) and specified outco- mes. Here, the logistic model, Cox regression and GEE model will be introduced. With the logistic regression model a binary outcome can be predicted or explained by the values of a set of predictor variables.131 The model produces odds ratios for each of the predictor variables, from which predicted probabilities for individual patients can be calculated. Cox regression is useful for modeling the time to a specified event.131 The model produces hazard ratios from a survival function which predicts the probability for the event to occur at a certain time point for given values of the covariates. Longitu- dinal regression with generalized estimating equations (GEE) can be used to analyze the longitudinal relationships between a continuous outcome and several time-depen- dent or time-independent covariates, measured repeatedly across time.132,133 The GEE model corrects for the fact that the repeated measurements in individual patients are correlated by specifying a working correlation structure, it is robust against violation of normality and it can provide a regression coefficient that can be interpreted both in terms of the cross-sectional relationship as well as the longitudinal relationship.134 Part II of this thesis is largely based on the methodology of systematic literature review (SLR). A SLR is a comprehensive search and appraisal of relevant studies on a specific topic, according to a pre-specified and explicit method, in order to summarize the effectiveness of an intervention.135 In contrast, a traditional non-systematic review is usually a qualitative and narrative summary of evidence written by experts in the field after more subjective collection of data. Within the context of a SLR, a meta-analysis is the statistical combination of multiple study results to produce a single effect size.136 Key steps in the process of SLR are formulation of a research question, building a search strategy for the literature search, screening of studies following pre-defined in- and exclusion criteria, methodological quality assessment, data extraction, analysis and fi- nally reporting of the results and conclusions.135 SLR forms an important part of Evidence-Based Medicine, as it summarizes existing evidence in order to develop up-to- date recommendations and guidelines, and it identifies gabs in our knowledge which can guide future research.
Aim and outline of the thesis
Important challenges still remain to further improve the treatment and thereby the outcome of RA, maybe even towards ‘cure’ or prevention of this up to now regarded chronic incurable disease. This thesis has focused on and made a start towards tackling several of these challenges and consists of three parts.
18 | Chapter 1
In part I the effect of methotrexate (MTX) as remission induction therapy to prevent the development from UA into RA was investigated in the first randomized placebo- controlled trial in UA: the PRObable rheumatoid arthritis Methotrexate versus Placebo Therapy (PROMPT) study. Chapter 2 introduces the PROMPT study and presents the pri- mary results of the effect of MTX on the progression from UA to RA (by fulfilling the 1987 criteria) and radiographic damage, including subanalyses on ACPA-positive and ACPA-negative patients. Chapter 3 investigates in more detail the effect of MTX versus placebo on disease activity, joint damage and functional disability in UA using longitu- dinal data analysis. In addition, this chapter examines a theoretical background for early intensive treatment of UA, by investigating the longitudinal relationships between DAS, HAQ and SHS. Chapter 4 reports on the rate and predictors of drug-free remission after one year MTX or placebo therapy. In addition, in the subgroup of UA patients who did not develop RA under MTX therapy, the outcome of stopping MTX and predictors for
‘non-remission’ (recurrent, persistent or progressive arthritis) were identified. In Chap- ter 5 the validity of the DAS as a method to measure disease activity in UA is tested.
In part II, the ‘current’ therapy of RA with MTX is a central theme. Results are given of the 2nd edition of the 3E Initiative (Evidence, Expertise, Exchange), a multinational project to promote evidence-based medicine in rheumatology by formulating recommen- dations based on systematic literature research and expert opinion. Chapter 6 summa- rizes the results of ten systematic literature reviews and presents the corresponding recommendations for the management of MTX in (mostly) RA patients. Chapter 7 shows the results of a systematic review on the optimal dosage and route of admini- stration of MTX in RA. Chapter 8 summarizes the existing evidence on the risk of liver toxicity during MTX treatment in RA.
Part III focuses on improved treatment of RA and presents post-hoc analyses of the BeSt study, which was a randomized clinical trial comparing four different DAS-driven treat- ment strategies. In Chapter 9 a matrix model is presented which predicts the risk for rapid radiographic progression in patients with specific combinations of risk factors, if treated with different treatment strategies, requiring only a limited number of easily accessible clinical variables. This model is a step towards a more individualized initial treatment choice in patients with recently diagnosed RA. Chapter 10 investigates the question whether DAS-driven therapy results in more sustained drug-free remission than non-DAS-driven therapy, by comparing the prevalence and predictors in the BeSt study (DAS-driven cohort) with the Leiden Early Arthritis Clinic (non-DAS-driven cohort).
In Chapter 11 the findings in this thesis are summarized and discussed.
1. Klareskog L, Catrina AI, Paget S. Rheumatoid arthritis. Lancet 2009;373:659-72.
2. Alamanos Y, Voulgari PV, Drosos AA.
Incidence and prevalence of rheumatoid arthritis, based on the 1987 American College of Rheumatology criteria: a systematic review. Semin Arthritis Rheum 2006;36:182-8.
3. Plenge RM. Rheumatoid arthritis genetics:
2009 update. Curr Rheumatol Rep 2009;
11:351-6.
4. Grassi W, De Angelis R, Lamanna G, et al. The clinical features of rheumatoid arthritis. Eur J Radiol 1998;27 Suppl 1:S18-S24.
5. Allaire S, Wolfe F, Niu J, et al. Contemporary prevalence and incidence of work disability associated with rheumatoid arthritis in the US. Arthritis Rheum 2008;59:474-80.
6. van der Heijde D, Landewe R, van Vollenho- ven R, et al. Level of radiographic damage and radiographic progression are determi- nants of physical function: a longitudinal analysis of the TEMPO trial. Ann Rheum Dis 2008;67:1267-70.
7. Welsing PM, van Gestel AM, Swinkels HL, et al. The relationship between disease activity, joint destruction, and functional capacity over the course of rheumatoid arthritis.
Arthritis Rheum 2001;44:2009-17.
8. Michaud K and Wolfe F. Comorbidities in rheumatoid arthritis. Best Pract Res Clin Rheumatol 2007;21:885-906.
9. Sokka T, Abelson B, Pincus T. Mortality in rheumatoid arthritis: 2008 update. Clin Exp Rheumatol 2008;26:S35-S61.
10. Young A and Koduri G. Extra-articular YY manifestations and complications of rheumatoid arthritis. Best Pract Res Clin Rheumatol 2007;21: 907-27.
11. Scott DL and Steer S. The course of establis- hed rheumatoid arthritis. Best Pract Res Clin Rheumatol 2007;21:943-67.
12. Garrod A. Treatise on nature and treatment of gout and rheumatic gout. London: Walton and Maberly 1859.
13. Storey GO, Comer M, Scott DL. Chronic arthritis before 1876: early British cases suggesting rheumatoid arthritis. Ann Rheum Dis 1994;53: 557-60.
14. Ropes MW, Bennett GA, Cobb S, et al. 1958 Revision of diagnostic criteria for rheuma-
toid arthritis. Bull Rheum Dis 1958;9(4):175-6.
15. Arnett FC, Edworthy SM, Bloch DF, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31(3):315-24.
16. Banal F, Dougados M, Combescure C, et al.F Sensitivity and specificity of the American College of Rheumatology 1987 criteria for the diagnosis of rheumatoid arthritis according to disease duration: a systematic literature review and meta-analysis. Ann Rheum Dis 2009;68:1184-91.
17. van der Linden MP, van der Woude D, Ioan-Facsinay A, et al. Value of anti-modified citrullinated vimentin and third-generation anti-cyclic citrullinated peptide compared with second-generation anti-cyclic citrullinated peptide and rheumatoid factor in predicting disease outcome in undifferen- tiated arthritis and rheumatoid arthritis.
Arthritis Rheum 2009;60:2232-41.
18. Liao KP, Batra KL, Chibnik L, et al. Anti-cyclic PP citrullinated peptide revised criteria for the classification of rheumatoid arthritis. Ann Rheum Dis 2008;67:1557-61.
19. Hulsemann JL and Zeidler H. Undifferentia- ted arthritis in an early synovitis out-patient clinic. Clin Exp Rheumatol 1995;13:37-43.
20. Harrison BJ, Symmons DP, Brennan P, et al.
Natural remission in inflammatory polyarthritis: issues of definition and prediction. Br J Rheumatol 1996;35:1096-100.
21. Verpoort KN, van Dongen H, Allaart CF, et al.VV Undifferentiated arthritis--disease course assessed in several inception cohorts. Clin Exp Rheumatol 2004;22:S12-S17.
22. Wolfe F, Ross K, Hawley DJ, et al. The prognosis of rheumatoid arthritis and undifferentiated polyarthritis syndrome in the clinic: a study of 1141 patients. J Rheumatol 1993;20:2005-9.
23. van Aken J, van Dongen H, le Cessie S, et al.
Comparison of long term outcome of patients with rheumatoid arthritis presenting with undifferentiated arthritis or with rheumatoid arthritis: an observational cohort study. Ann Rheum Dis 2006;65:20-5.
24. Nell VP, Machold KP, Eberl G, et al. Benefit of very early referral and very early therapy with disease-modifying antirheumatic
References
20 | Chapter 1
drugs in patients with early rheumatoid arthritis. Rheumatology (Oxford) 2004;43:906-14.
25. Finckh A, Liang MH, van Herckenrode CM, et al. Long-term impact of early treatment on radiographic progression in rheumatoid arthritis: A meta-analysis. Arthritis Rheum 2006;55:864-72.
26. van der Heide A, Jacobs JW, Bijlsma JW, et al.
The effectiveness of early treatment with
“second-line” antirheumatic drugs. A randomized, controlled trial. Ann Intern Med 1996;124:699-707.
27. Quinn MA and Emery P. Window of opportu- nity in early rheumatoid arthritis: possibility of altering the disease process with early intervention. Clin Exp Rheumatol 2003;21:S154-S157.
28. van der Helm-van Mil AH, le Cessie S, van Dongen H, et al. A prediction rule for disease outcome in patients with recent-onset undifferentiated arthritis: how to guide individual treatment decisions. Arthritis Rheum 2007;56:433-40.
29. Visser H, le Cessie S, Vos K, et al. How to diagnose rheumatoid arthritis early: a prediction model for persistent (erosive) arthritis. Arthritis Rheum 2002;46:357-65.
30. van Aken J, van Bilsen JH, Allaart CF, et al. The Leiden Early Arthritis Clinic. Clin Exp Rheumatol 2003;21:S100-S105.
31. Nielen MM, van Schaardenburg D, Reesink HW, et al. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors.
Arthritis Rheum 2004;50:380-6.
32. Rantapaa-Dahlqvist S, de Jong BA, Berglin E, et al. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis.
Arthritis Rheum 2003;48:2741-9.
33. van Gaalen FA, Linn-Rasker SP, van Venrooij WJ, et al. Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study. Arthritis Rheum 2004;50(3):709-15.
34. Syversen SW, Gaarder PI, Goll GL, et al. High anti-cyclic citrullinated peptide levels and an algorithm of four variables predict radiograp- hic progression in patients with rheumatoid arthritis: results from a 10-year longitudinal study. Ann Rheum Dis 2008;67:212-7.
35. Kuhn KA, Kulik L, Tomooka B, et al. Antibodies
against citrullinated proteins enhance tissue injury in experimental autoimmune arthritis.
J Clin Invest 2006;116:961-73.
36. van Gaalen F, Ioan-Facsinay A, Huizinga TW, et al. The devil in the details: the emerging role of anticitrulline autoimmunity in rheumatoid arthritis. J Immunol 2005;175:5575-80.
37. van Oosterhout M, Bajema I, Levarht EW, et al.
Differences in synovial tissue infiltrates between anti-cyclic citrullinated peptide- positive rheumatoid arthritis and anti-cyclic citrullinated peptide-negative rheumatoid arthritis. Arthritis Rheum 2008;58:53-60.
38. van der Helm-van Mil AH, Verpoort KN, le Ces- sie S, et al. The HLA-DRB1 shared epitope alleles differ in the interaction with smoking and predisposition to antibodies to cyclic citrullinated peptide. Arthritis Rheum 2007;56:425-32.
39. Williams HJ, Willkens RF, Samuelson CO, Jr., et al. Comparison of low-dose oral pulse methotrexate and placebo in the treatment of rheumatoid arthritis. A controlled clinical trial. Arthritis Rheum 1985;28:721-30.
40. Weinblatt ME, Kaplan H, Germain BF, et al.
Methotrexate in rheumatoid arthritis. A five- year prospective multicenter study. Arthritis Rheum 1994;37:1492-8.
41. Hoffmeister RT. Methotrexate therapy in rheumatoid arthritis: 15 years experience.
Am J Med 1983;75:69-73.
42. Aletaha D, Stamm T, Kapral T, et al. Survival and effectiveness of leflunomide compared with methotrexate and sulfasalazine in rheumatoid arthritis: a matched observatio- nal study. Ann Rheum Dis 2003;62:944-51.
43. Maetzel A, Wong A, Strand V, et al. Meta- analysis of treatment termination rates among rheumatoid arthritis patients receiving disease-modifying antirheumatic drugs. Rheumatology (Oxford) 2000;39:
975-81.
44. Aletaha D and Smolen JS. Effectiveness profiles and dose dependent retention of traditional disease-modifying antirheumatic drugs for rheumatoid arthritis. An observati- onal study. J Rheumatol 2002;29:1631-8.
45. Strand V, Cohen S, Schiff M, et al. Treatment of active rheumatoid arthritis with leflunomide compared with placebo and methotrexate. Leflunomide Rheumatoid Arthritis Investigators Group. Arch Intern Med 1999;159:2542-50.
46. Weinblatt ME, Kaplan H, Germain BF, et al.
Methotrexate in rheumatoid arthritis. A five-year prospective multicenter study.
Arthritis Rheum 1994;37:1492-8.
47. Wessels JA, Huizinga TW, Guchelaar HJ.
Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritis. Rheumatology (Oxford) 2008; 47:249-55.
48. Wessels JA, van der Kooij SM, le Cessie S, et al. A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent-onset rheumatoid arthritis. Arthritis Rheum 2007;56:1765-75.
49. Kooloos WM, Wessels JA, van der Kooij SM, et al. Optimalization of the clinical pharmaco- genetic model to predict methotrexate treatment response: the influence of the number of haplotypes of MTHFR 1298A-677C alleles on probability to respond. Ann Rheum Dis 2009;68:1371.
50. Ranganathan P. An update on methotrexate pharmacogenetics in rheumatoid arthritis.
Pharmacogenomics 2008;9:439-51.
51. Pincus T, Yazici Y, Sokka T, et al. Methotrexate as the “anchor drug” for the treatment of early rheumatoid arthritis. Clin Exp Rheuma- tol 2003;21:S179-S185.
52. Combe B, Landewe R, Lukas C, et al. EULAR recommendations for the management of early arthritis: report of a task force of the European Standing Committee for Internatio- nal Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis 2007;66:34-45.
53. Pope JE, Hong P, Koehler BE. Prescribing trends in disease-modifying antirheumatic drugs for rheumatoid arthritis: a survey of practicing Canadian rheumatologists. J Rheumatol 2002;29:255-60.
54. Criswell LA and Henke CJ. What explains the variation among rheumatologists in their use of prednisone and second line agents for the treatment of rheumatoid arthritis? J Rheumatol 1995;22:829-35.
55. Suarez-Almazor ME, Spooner CH, Belseck E, et al. Auranofin versus placebo in rheumatoid arthritis. Cochrane Database Syst Rev 2000;CD002048.
56. Clark P, Tugwell P, Bennet K, Bombardier C, et al. Injectable gold for rheumatoid arthritis.
Cochrane Database Syst Rev 2000;CD000520.
57. Rau R, Herborn G, Menninger H, et al.
Comparison of intramuscular methotrexate and gold sodium thiomalate in the treatment of early erosive rheumatoid arthritis: 12
month data of a double-blind parallel study of 174 patients. Br J Rheumatol 1997;36:
345-52.
58. Hamilton J, McInnes IB, Thomson EA, et al.
Comparative study of intramuscular gold and methotrexate in a rheumatoid arthritis population from a socially deprived area. Ann Rheum Dis 2001;60:566-72.
59. McConkey B, Amos RS, Durham S, et al.
Sulphasalazine in rheumatoid arthritis. Br Med J 1980;280:442-4.
60. Dougados M, Combe B, Cantagrel A, et al.
Combination therapy in early rheumatoid arthritis: a randomised, controlled, double blind 52 week clinical trial of sulphasalazine and methotrexate compared with the single components. Ann Rheum Dis 1999;58:220-5.
61. Haagsma CJ, van Riel PL, de Jong AJ, et al.
Combination of sulphasalazine and methotrexate versus the single components in early rheumatoid arthritis: a randomized, controlled, double-blind, 52 week clinical trial.
Br J Rheumatol 1997;36:1082-8.
62. Capell HA, Madhok R, Porter DR, et al.
Combination therapy with sulfasalazine and methotrexate is more effective than either drug alone in patients with rheumatoid arthritis with a suboptimal response to sulfasalazine: results from the double-blind placebo-controlled MASCOT study. Ann Rheum Dis 2007;66:235-41.
63. O’Dell JR, Haire CE, Erikson N, et al. Treatment of rheumatoid arthritis with methotrexate alone, sulfasalazine and hydroxychloroquine, or a combination of all three medications. N Engl J Med 1996;334:1287-91.
64. O’Dell JR, Leff R, Paulsen G, et al. Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a combination of the three medications: results of a two-year, randomi- zed, double-blind, placebo-controlled trial.
Arthritis Rheum 2002;46:1164-70.
65. Mottonen T, Hannonen P, Leirisalo-Repo M, et al. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group. Lancet 1999;353:1568-73.
66. Osiri M, Shea B, Robinson V, et al. Suarez- Almazor M, Strand V, Tugwell P et al.
Leflunomide for treating rheumatoid arthritis. Cochrane Database Syst Rev 2003;CD002047.
67. Kremer JM, Genovese MC, Cannon GW, et al.
22 | Chapter 1
Concomitant leflunomide therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 2002;137:726-33.
68. Weinblatt ME, Kremer JM, Coblyn JS, et al.
Pharmacokinetics, safety, and efficacy of combination treatment with methotrexate and leflunomide in patients with active rheumatoid arthritis. Arthritis Rheum 1999;42:1322-8.
69. Kirwan JR, Bijlsma JW, Boers M, et al. Effects of glucocorticoids on radiological progression in rheumatoid arthritis. Cochrane Database Syst Rev 2007;CD006356.
70. Wassenberg S, Rau R, Steinfeld P, et al. Very low-dose prednisolone in early rheumatoid arthritis retards radiographic progression over two years: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum 2005; 52:3371-80.
71. van Everdingen AA, Jacobs JW, Siewertsz Van Reesema DR, et al. Low-dose prednisone therapy for patients with early active rheumatoid arthritis: clinical efficacy, disease-modifying properties, and side effects: a randomized, double-blind, placebo-controlled clinical trial. Ann Intern Med 2002;136:1-12.
72. Landewe RB, Boers M, Verhoeven AC, et al.
COBRA combination therapy in patients with early rheumatoid arthritis: long-term structural benefits of a brief intervention.
Arthritis Rheum 2002;46:347-56.
73. van Tuyl LH, Boers M, Lems WF, et al. Survival, comorbidities and joint damage 11 years after the COBRA combination therapy trial in early rheumatoid arthritis. Ann Rheum Dis 2009;
[Epub ahead of print]
74.
77 van Tuyl LH, Plass AM, Lems WF, et al.
Discordant perspectives of rheumatologists and patients on COBRA combination therapy in rheumatoid arthritis. Rheumatology (Oxford) 2008;47:1571-6.
75. Van der Goes MC, Jacobs JW, Boers M, et al. VV Patients’ and rheumatologists’ perspectives on glucocorticoids an exercise to improve the implementation of the EULAR recommenda- tions on the management of systemic glucocorticoid therapy in rheumatic diseases.
Ann Rheum Dis 2009; [Epub ahead of print]
76. Da Silva JA, Jacobs JW, Bijlsma JW. Revisiting the toxicity of low-dose glucocorticoids: risks and fears. Ann N Y Acad Sci 2006;1069:275-88.
77. Da Silva JA, Jacobs JW, Kirwan JR, et al. Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data. Ann Rheum Dis 2006;65:285-93.
78. Hoes JN, Jacobs JW, Boers M, et al. EULAR evidence-based recommendations on the management of systemic glucocorticoid therapy in rheumatic diseases. Ann Rheum Dis 2007;66:1560-7.
79. Brennan FM, Chantry D, Jackson A, et al.
Inhibitory effect of TNF alpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet 1989;2:244-7.
80. Breedveld FC, Weisman MH, Kavanaugh AF, et al. The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment.
Arthritis Rheum 2006;54:26-37.
81. Emery P, Breedveld FC, Hall S, et al. Compari- son of methotrexate monotherapy with a combination of methotrexate and etaner- cept in active, early, moderate to severe rheumatoid arthritis (COMET): a rando- mised, double-blind, parallel treatment trial.
Lancet 2008;372:375-82.
82. Genovese MC, Bathon JM, Martin RW, et al.
Etanercept versus methotrexate in patients with early rheumatoid arthritis: two-year radiographic and clinical outcomes. Arthritis Rheum 2002;46:1443-50.
83. Keystone EC, Kavanaugh AF, Sharp JT, et al.
Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized, placebo-controlled, 52-week trial. Arthritis Rheum 2004;50:1400-11.
84. Klareskog L, van der Heijde D, de Jager JP, et al. Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 2004;363:675-81.
85. Lipsky PE, van der Heijde DM, St Clair EW, et al. Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-
Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med 2000;343:1594-602.
86. St Clair EW, van der Heijde DM, Smolen JS, et al. Combination of infliximab and metho- trexate therapy for early rheumatoid arthritis:
a randomized, controlled trial. Arthritis Rheum 2004;50:3432-43.
87. Kievit W, Adang EM, Fransen J, et al. The effectiveness and medication costs of three anti-tumour necrosis factor alpha agents in the treatment of rheumatoid arthritis from prospective clinical practice data. Ann Rheum Dis 2008;67:1229-34.
88. Dixon WG, Hyrich KL, Watson KD, et al.
Drug-specific risk of tuberculosis in patients with rheumatoid arthritis treated with anti-TNF therapy: results from the British Society for Rheumatology Biologics Register (BSRBR). Ann Rheum Dis 2010;69:522-8.
89. Askling J and Dixon W. The safety of anti-tumour necrosis factor therapy in rheuma-toid arthritis. Curr Opin Rheumatol 2008;20:138-44.
90. Statkute L and Ruderman EM. Novel TNF antagonists for the treatment of rheumatoid arthritis. Expert Opin Investig Drugs 2010;19:105-15.
91. Emery P, Keystone E, Tony HP, et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals:
results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis 2008;67:1516-23.
92. Jiang Y, Genant HK, Watt I, et al. A multicen- ter, double-blind, dose-ranging, randomized, placebo-controlled study of recombinant human interleukin-1 receptor antagonist in patients with rheumatoid arthritis:
radiologic progression and correlation of Genant and Larsen scores. Arthritis Rheum 2000;43:1001-9.
93. Cohen SB, Emery P, Greenwald MW, et al.
Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy:
Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum 2006;54:2793-806.
94. Kremer JM, Westhovens R, Leon M, et al. Treat- ment of rheumatoid arthritis by selective
inhibition of T-cell activation with fusion protein CTLA4Ig. N Engl J Med 2003;349:
1907-15.
95. Sokka T and Hannonen P. Utility of disease- modifying antirheumatic drugs in “sawtooth”
strategy. A prospective study of early rheumatoid arthritis patients up to 15 years.
Ann Rheum Dis 1999;58:618-22.
96. Fries JF, Williams CA, Ramey DR, et al. The relative toxicity of alternative therapies for rheumatoid arthritis: implications for the therapeutic progression. Semin Arthritis Rheum 1993;23:68-73.
97. Scott DL, Symmons DP, Coulton BL, et al.
Long-term outcome of treating rheumatoid arthritis: results after 20 years. Lancet 1987;1:1108-11.
98. van Aken J, Lard LR, le Cessie S, et al. Radiologi- cal outcome after four years of early versus delayed treatment strategy in patients with recent onset rheumatoid arthritis. Ann Rheum Dis 2004;63:274-9.
99. Boers M, Verhoeven AC, Markusse HM, et al.
Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet
1997;350:309-18.
100. Goekoop-Ruiterman YP, Vries-Bouwstra JK, Allaart CF, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum 2005;52:
3381-90.
101. van der Heijde D, Klareskog L, Rodriguez- Valverde V, et al. Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis:
two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial. Arthritis Rheum 2006;54:1063-74.
102. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Kerstens PJ, et al. DAS-driven therapy versus routine care in patients with recent-onset active rheumatoid arthritis. Ann Rheum Dis 2010;69:65-9.
103. Grigor C, Capell H, Stirling A, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial.
Lancet 2004;364:263-9.
104. Schoels M, Knevel R, Aletaha D, et al. Evidence
24 | Chapter 1
for treating rheumatoid arthritis to target:
results of a systematic literature search. Ann Rheum Dis 2010;69:638-43.
105. Verstappen SM, Jacobs JW, van der Veen MJ,VV et al. Intensive treatment with methotrexate in early rheumatoid arthritis: aiming for remission. Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA, an open-label strategy trial). Ann Rheum Dis 2007;66:1443-9.
106. van der Kooij SM, Goekoop-Ruiterman YP, de Vries-Bouwstra JK, et al. Drug-free remission, functioning and radiographic damage after 4 years of response-driven treatment in patients with recent-onset rheumatoid arthritis. Ann Rheum Dis 2009;68:914-21.
107. Felson DT, Anderson JJ, Boers M, et al. The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. The Committee on Outcome Measures in Rheumatoid Arthritis Clinical Trials.
Arthritis Rheum 1993;36:729-40.
108. Aletaha D, Landewe R, Karonitsch T, et al.
Reporting disease activity in clinical trials of patients with rheumatoid arthritis: EULAR/
ACR collaborative recommendations.
Arthri- tis Rheum 2008;59:1371-7.
109. Fuchs HA and Pincus T. Reduced joint counts in controlled clinical trials in rheumatoid arthritis. Arthritis Rheum 1994;37:470-5.
110. Prevoo ML, van Riel PL, van ‘t Hof MA, et al.
Validity and reliability of joint indices. A longitudinal study in patients with recent onset rheumatoid arthritis. Br J Rheumatol 1993;32:589-94.
111. Ritchie DM, Boyle JA, McInnes JM, et al.
Clinical studies with an articular index for the assessment of joint tenderness in patients with rheumatoid arthritis. Q J Med 1968;37:393-406.
112. Joos E, Peretz A, Beguin S, et al. Reliability and reproducibility of visual analogue scale and numeric rating scale for therapeutic evaluation of pain in rheumatic patients. J Rheumatol 1991;18:1269-70.
113. van der Heijde DM, van ’t Hof MA, van Riel PL, et al. Development of a disease activity score based on judgment in clinical practice by rheumatologists. J Rheumatol 1993;20:579-81.
114. Felson DT, Anderson JJ, Boers M, et al.
American College of Rheumatology.
Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum
1995;38:727-35.
115. van Gestel AM, Prevoo ML, van ‘t Hof MA, et al. Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis.
Comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism Criteria. Arthritis Rheum 1996;39:34-40.
116. Fries JF, Spitz P, Kraines RG, et al. Measure- ment of patient outcome in arthritis.
Arthritis Rheum 1980;23:137-45.
117. Siegert CE, Vleming LJ, Vandenbroucke JP, et al. Measurement of disability in Dutch rheumatoid arthritis patients. Clin Rheuma- tol 1984;3:305-9.
118. Pope JE, Khanna D, Norrie D, et al. The minimally important difference for the health assessment questionnaire in rheumatoid arthritis clinical practice is smaller than in randomized controlled trials.
J Rheumatol 2009;36:254-9.
119. Wells GA, Tugwell P, Kraag GR, et al.
Minimum important difference between patients with rheumatoid arthritis: the patient’s perspective. J Rheumatol 1993;20:557-60.
120. Wolfe F, Michaud K, Gefeller O, et al.
Predicting mortality in patients with rheumatoid arthritis. Arthritis Rheum 2003;48:1530-42.
121. Drossaers-Bakker KW, de Buck M, van Zeben D, et al. Long-term course and outcome of functional capacity in rheumatoid arthritis:
the effect of disease activity and radiologic damage over time. Arthritis Rheum 1999;42:1854-60.
122. van der Heijde D. How to read radiographs according to the Sharp/van der Heijde method. J Rheumatol 2000;27:261-3.
123. Bruynesteyn K, Boers M, Kostense P, et al.
Deciding on progression of joint damage in paired films of individual patients: smallest detectable difference or change. Ann Rheum Dis 2005;64:179-82.
124. Landewe R and van der Heijde D. Radiograp- hic progression depicted by probability plots: presenting data with optimal use of individual values. Arthritis Rheum 2004;50:699-706.
125. Odegard S, Landewe R, van der Heijde D, et al. Association of early radiographic damage with impaired physical function in
