Showing papers by "Daniel Aletaha published in 2011"

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs

Abstract: Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects, are described. The recommendations are based on evidence from five systematic literature reviews (SLRs) performed for synthetic DMARDs, biological DMARDs, GCs, treatment strategies and economic issues. The SLR-derived evidence was discussed and summarised as an expert opinion in the course of a Delphi-like process. Levels of evidence, strength of recommendations and levels of agreement were derived. Fifteen recommendations were developed covering an area from general aspects such as remission/low disease activity as treatment aim via the preference for methotrexate monotherapy with or without GCs vis-à-vis combination of synthetic DMARDs to the use of biological agents mainly in patients for whom synthetic DMARDs and tumour necrosis factor inhibitors had failed. Cost effectiveness of the treatments was additionally examined. These recommendations are intended to inform rheumatologists, patients and other stakeholders about a European consensus on the management of RA with DMARDs and GCs as well as strategies to reach optimal outcomes of RA, based on evidence and expert opinion.

Treating rheumatoid arthritis to target: recommendations of an international task force (vol 69, pg 631, 2010)

Abstract: Background Aiming at therapeutic targets has reduced the risk of organ failure in many diseases such as diabetes or hypertension. Such targets have not been defined for rheumatoid arthritis (RA). Objective To develop recommendations for achieving optimal therapeutic outcomes in RA. Methods A task force of rheumatologists and a patient developed a set of recommendations on the basis of evidence derived from a systematic literature review and expert opinion; these were subsequently discussed, amended and voted upon by >60 experts from various regions of the world in a Delphi-like procedure. Levels of evidence, strength of recommendations and levels of agreement were derived. Results The treat-to-target activity resulted in 10 recommendations. The treatment aim was defined as remission with low disease activity being an alternative goal in patients with long-standing disease. Regular follow-up (every 1–3 months during active disease) with appropriate therapeutic adaptation to reach the desired state within 3 to a maximum of 6 months was recommended. Follow-up examinations ought to employ composite measures of disease activity which include joint counts. Additional items provide further details for particular aspects of the disease. Levels of agreement were very high for many of these recommendations (≥9/10). Conclusion The 10 recommendations are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA based on evidence and expert opinion.

American College of Rheumatology/European League Against Rheumatism Provisional Definition of Remission in Rheumatoid Arthritis for Clinical Trials

Abstract: Objective Remission in rheumatoid arthritis (RA) is an increasingly attainable goal, but there is no widely used defi nition of remission that is stringent but achievable and could be applied uniformly as an outcome measure in clinical trials. This work was undertaken to develop such a defi nition. Methods A committee consisting of members of the American College of Rheumatology, the European League Against Rheumatism, and the Outcome Measures in Rheumatology Initiative met to guide the process and review prespecifi ed analyses from RA clinical trials. The committee requested a stringent defi nition (little, if any, active disease) and decided to use core set measures including, as a minimum, joint counts and levels of an acute-phase reactant to defi ne remission. Members were surveyed to select the level of each core set measure that would be consistent with remission. Candidate defi nitions of remission were tested, including those that constituted a number of individual measures of remission (Boolean approach) as well as defi nitions using disease activity indexes. To select a defi nition of remission, trial data were analysed to examine the added contribution of patient-reported outcomes and the ability of candidate measures to predict later good radiographic and functional outcomes. Results Survey results for the defi nition of remission suggested indexes at published thresholds and a count of core set measures, with each measure scored as 1 or less (eg, tender and swollen joint counts, C reactive protein (CRP) level, and global assessments on a 0–10 scale). Analyses suggested the need to include a patientreported measure. Examination of 2-year follow-up data suggested that many candidate defi nitions performed comparably in terms of predicting later good radiographic and functional outcomes, although 28-joint Disease Activity Score–based measures of remission did not

European League Against Rheumatism recommendations for the inclusion of patient representatives in scientific projects

Abstract: Objective: To develop recommendations to enable successful inclusion of the patient perspective in European League Against Rheumatism (EULAR)-funded scientific research projects. Methods: The EULAR standardised operational procedures for guideline development were followed. A systematic literature review was presented during a first task force meeting, including 3 rheumatologists, 1 rheumatologist/epidemiologist, 2 allied health professionals, 2 representatives of arthritis research organisations and 7 patient representatives, resulting in 38 statements. A Delphi method was carried out to reduce and refine the statements and agree on a set of eight. Next, a survey among a wider group of experts, professionals and patient representatives (n=42), was completed. Feedback from this wider group was discussed at the second meeting and integrated in the final wording of the recommendations. Subsequently, the level of agreement of the group of experts (n=81) was re-evaluated. Results: The project resulted in a definition of patient research partner and agreement on a set of eight recommendations for their involvement in research projects. These recommendations provide practical guidance for organising patient participation, capturing (1) the role of patient research partners, (2) phase of involvement, (3) the recommended number, (4) recruitment, (5) selection, (6) support, (7) training and (8) acknowledgement. Conclusion: Collaboration between patients and professionals in research is relatively new. Trials or effectiveness studies are not yet available. Nevertheless, it is possible to define recommendations for the inclusion of patients in research following a solid expert opinion based consensus process.

Physical disability in rheumatoid arthritis is associated with cartilage damage rather than bone destruction

Abstract: Background Joint destruction in rheumatoid arthritis is comprised of cartilage and bone damage, which can be evaluated radiographically separately by the joint space narrowing (JSN) and erosion (ERO) scores. It is currently unclear to which extent these components affect irreversible functional disability. The aim of the present work was to determine these contributions. Methods Data, kindly provided by the sponsors, was evaluated from several randomised controlled clinical trials on adalimumab, etanercept, infliximab and leflunomide. Patients who reached stringent remission according to the Simplified Disease Activity Index (SDAI≤3.3) were extracted to eliminate the activity related (ie, reversible) component of disability. In these patients, residual Health Assessment Questionnaire Disability Index (HAQ-DI) score at the time of remission (to reflect the level of ‘irreversible’ disability) was determined and related to baseline measures of ERO and JSN scores univariately, by stratification and in adjusted regression models. Results A total of 748 patients who achieved a state of remission were analysed (16.3% of the total pooled population of 4602 patients). In the univariate analyses, mean residual HAQ-DI values in remission were significantly larger in higher tertiles of JSN and ERO (ERO: 0.21, 0.25, 0.35; JSN: 0.19, 0.24, 0.39; p Conclusions Cartilage damage appears to be the more clearly associated with irreversible physical disability than bony damage. These data suggest that particular attention should be given to therapeutic interference with cartilage destruction.

Interleukin-6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: The role of acute-phase reactants

Abstract: Objective To determine the effects of tocilizumab on rheumatoid arthritis (RA) disease activity and remission assessment, using measures that do or do not comprise acute-phase reactants. Methods Simplified Disease Activity Index (SDAI) scores, Clinical Disease Activity Index (CDAI) scores, and the Disease Activity Score in 28 joints (DAS28) were calculated using data from tocilizumab trials in patients with RA in whom disease had remained active despite treatment with disease-modifying antirheumatic drugs. The CDAI does not contain an acute-phase reactant component. Disease activity states, including remission, were defined using established cut points; for the DAS28, an alternative cut point of <2.4 was also used. Results Changes in the DAS28, the SDAI score, and the CDAI score among patients receiving tocilizumab were significantly higher than those among patients receiving placebo, and the magnitude of these changes was similar for the SDAI and the CDAI. Among patients who achieved 50% improvement in disease activity according to the American College of Rheumatology criteria, only ∼20% required a reduction in acute-phase reactant values in order to fulfill the criteria. However, DAS28 remission rates were higher (even when using the lower cut point) than the SDAI and CDAI remission rates. Only a minority of tocilizumab-treated patients with DAS28 remission also had disease remission according to the SDAI (26%) or CDAI (∼21%). With infliximab treatment, SDAI and CDAI remission rates were of the same magnitude as those observed with tocilizumab treatment, and DAS28 remission rates were lower. Tocilizumab-treated patients with DAS28 remission but without CDAI remission had significantly higher swollen joint counts but lower erythrocyte sedimentation rates (ESRs) compared with patients with SDAI or CDAI remission. Conclusion Disease activity in RA is reduced by tocilizumab treatment, irrespective of the type of composite measure used to evaluate disease activity. Remission rates were much higher using the DAS28 compared with the SDAI and CDAI, due to the high weight of the ESR in the DAS28 and the effect of tocilizumab on the ESR. Using the stringent SDAI and CDAI criteria, however, remission rates in patients treated with tocilizumab were in the same range as those seen in patients treated with tumor necrosis factor inhibitors.

Joint damage in rheumatoid arthritis progresses in remission according to the Disease Activity Score in 28 joints and is driven by residual swollen joints.

Abstract: Objective Remission has been defined as the ultimate target for patients with rheumatoid arthritis. The Disease Activity Score in 28 joints (DAS28) has been criticized for the amount of disease activity that remains in patients despite their achieving DAS28 remission. This study was undertaken to investigate the significance of residual inflammation in remission in relation to radiographic progression. Methods We pooled 1-year clinical data, kindly provided by the respective sponsors, on 864 patients in methotrexate monotherapy arms of recent pivotal trials. We identified patients who had attained persistent DAS28 remission from month 6 through month 12 (a DAS286–12 of <2.6). Among these patients we then assessed radiographic progression in total Sharp/van der Heijde scores (SHS) from baseline to 12 months between those with residual joint swelling (defined as a swollen joint count from month 6 through month 12 [SJC6–12] of ≥2) and those without residual joint swelling (defined as an SJC6–12 of <2). Results One hundred fourteen patients (13.2%) achieved a DAS286–12 of 0.5/year was significantly lower among those without joint swelling than among those with joint swelling (27.2% versus 50.0%; P = 0.039). DAS28 remitters without joint swelling showed progression comparable to that in the total group of remitters by the Simplified Disease Activity Index (remission defined as ≤3.3) and Clinical Disease Activity Index (remission defined as ≤2.8), namely, 0.2 versus −0.07 versus 0.16, respectively (P = 0.66). Conclusion Radiographic progression with nonbiologic treatment is minimal only when patients in DAS28 remission have no persistent residual joint swelling. Under these conditions, progression is comparable to that in patients with disease in remission according to other disease activity indices.

Comorbidity affects all domains of physical function and quality of life in patients with rheumatoid arthritis

Abstract: Objective. Comorbidities have been reported to influence physical function, but it is not clear which activities are predominantly impaired, or which other domains of health status are affected in addition to physical function. In this study, we investigated the impact of comorbidities on individual activities of daily living, and other aspects of quality of live in patients with RA. Methods. In 380 patients with established RA, we quantified comorbidity levels according to the age-adjusted Charlson Comorbidity Index (CCIA) and functional disability by serial measures of the HAQ over 1 year. In a subset of 185 patients, we assessed quality of life using Short Form-36 (SF-36). To analyse the relationship between comorbidities, different activities of daily living and health status, we divided patients into four subgroups of CCIA and performed analysis of variance (ANOVA) and multivariable general linear regression models adjusted for gender, disease duration and disease activity. Results. ANOVA showed significant (P < 0.03) increase of disability within each domain of HAQ with increasing level of comorbidity. Similar results were observed using the physical component score (P = 0.003) of the SF-36 and its domains, whereas mental component score (P = 0.31) and its domains were unaffected by comorbidities. In a sub-analysis stratifying patients into different levels of disease activity, we found increase in almost all domains of HAQ within respective groups of CCIA. Conclusions. Activities of daily living represented by HAQ are equally affected by comorbidities. More generally, health status was only affected with respect to its physical but not its mental domains.

Treating Rheumatoid Arthritis to Target: multinational recommendations assessment questionnaire

Abstract: Aim: To measure the level of agreement and application of 10 international recommendations for treating rheumatoid arthritis (RA) to a target of remission/low disease activity. Methods: A 10-point Likert scale (1=fully disagree, 10=fully agree) measured the level of agreement with each of 10 recommendations. A 4-point Likert scale (never, not very often, very often, always) assessed the degree to which each recommendation was being applied in current daily practice. If respondents answered 'never' or 'not very often', they were asked whether they would change their practice according to the particular recommendation. Results: A total of 1901 physicians representing 34 countries participated. Both agreement with and application of recommendations was high. With regard to application of recommendations in daily practice, the majority of responses were 'always' and 'very often'. A significant percentage of participants who were currently not applying these recommendations in clinical practice were willing to change their practice according to the recommendations. Conclusion: The results of this survey demonstrated great support of 'Treating RA to Target' recommendations among the international rheumatology community. Additional efforts may be needed to encourage application of the recommendations among certain clinicians who are resistant to changing their practice.

Patient-reported outcomes in chronic gout: a report from OMERACT 10.

Abstract: Objective. To summarize the endorsement of measures of patient-reported outcome (PRO) domains in chronic gout at the 2010 Outcome Measures in Rheumatology Meeting (OMERACT 10). Methods. During the OMERACT 10 gout workshop, validation data were presented for key PRO domains including pain [pain by visual analog scale (VAS)], patient global (patient global VAS), activity limitation [Health Assessment Questionnaire-Disability Index (HAQ-DI)], and a disease-specific measure, the Gout Assessment Questionnaire version 2.0 (GAQ v2.0). Data were presented on all 3 aspects of the OMERACT filters of truth, discrimination, and feasibility. One PRO, health-related quality of life measurement with the Medical Outcomes Study Short-form 36 (SF-36), was previously endorsed at OMERACT 9. Results. One measure for each of the 3 PRO of pain, patient global, and activity limitation was endorsed by > 70% of the OMERACT delegates to have appropriate validation data. Specifically, pain measurement by VAS was endorsed by 85%, patient global assessment by VAS by 73%, and activity limitation by HAQ-DI by 71%. GAQ v2.0 received 30% vote and was not endorsed due to several concerns including low internal consistency and lack of familiarity with the measure. More validation studies are needed for this measure. Conclusion. With the endorsement of one measure each for pain, patient global, SF-36, and activity limitation, all 4 PRO for chronic gout have been endorsed. Future validation studies are needed for the disease-specific measure, GAQ v2.0. Validation for PRO for acute gout will be the focus of the next validation exercise for the OMERACT gout group.

Changes in patient characteristics in anti-tumour necrosis factor clinical trials for rheumatoid arthritis: results of an analysis of the literature over the past 16 years

Abstract: Objective To evaluate changes in baseline patient characteristics and entry criteria of randomised, controlled studies of tumour necrosis factor alpha (TNFα) inhibitors in rheumatoid arthritis (RA) patients. Methods A systematic literature review was performed using predefi ned inclusion criteria to identify randomised, double-blind, controlled trials that evaluated TNFα inhibitors in adult RA patients. Entry criteria and baseline clinical characteristics were evaluated over time for methotrexate-experienced and methotrexate-naive study populations. Enrolment start date for each trial was the time metric. The anchor time was the study with the earliest identifi able enrolment start date. Results 44 primary publications (reporting the primary study endpoint) from 1993 to 2008 met the inclusion criteria. Enrolment start dates of August 1993 and May 1997 were identifi ed as time anchors for the 37 methotrexate-experienced studies and the seven methotrexate-naive studies, respectively. In methotrexate-experienced trials, no signifi cant change was observed over the years included in this study in any inclusion criteria (including swollen joint counts and C-reactive protein (CRP)), but a signifi cant decrease over time was observed in the baseline swollen joint count, CRP and total Sharp or van der Heijde modifi ed Sharp score, but not in baseline tender joint counts. In the methotrexate-naive studies, signifi cant decreases over the years were observed in swollen joint and tender joint inclusion criteria, but not in baseline tender joint count, baseline CRP, CRP inclusion criteria or baseline total Sharp or van der Heijde modifi ed Sharp score. Conclusion Inclusion criteria and baseline characteristics of RA patients enrolled in studies of TNFα inhibitors have changed, with more recent trials enrolling cohorts with lower disease activity, especially in methotrexate-experienced trials.

Reporting of long-term extension studies: lack of consistency calls for consensus

Abstract: Double-blind, randomised controlled studies represent the gold-standard approach to determine the safety and efficacy of therapeutic interventions. In chronic conditions such as rheumatoid arthritis (RA), long-term data are vital to confirm maintenance of effect and identify potential safety signals. The recent introduction of numerous biological therapies for RA has been followed by various long-term extension (LTE) studies. Although useful, the design and method of analysis in such studies vary significantly, partly due to their complexity. This viewpoint highlights general considerations needed when undertaking a LTE study and illustrates the lack of consistency in studies of RA to date. It addresses issues of selection bias, patient discontinuation and missing data. Although used for safety reporting, the lack of adequate powering makes LTE studies of limited benefit. Ethical considerations and challenges are highlighted, including potential conflicts of interest. Finally, the authors suggest the need for consensus to ensure more reliable interpretation and application of data for clinical practice. Following the development of guidelines on reporting of clinical trials in RA and more recently, registry data, a similar approach for LTE studies would be a useful endeavour.

Rheumatoid arthritis near remission: clinical rather than laboratory inflammation is associated with radiographic progression

Abstract: Background Disease activity in rheumatoid arthritis (RA) can be measured clinically (eg, swollen joint count (SJC)) or systemically (eg, C reactive protein (CRP)). In general, both contribute to the progression of joint damage, but the relevance of residual inflammation in patients near remission is unclear. Objective To determine the independent contribution of SJC and CRP to progression of joint damage in patients near remission. Methods Data from methotrexate monotherapy arms of the ASPIRE, ERA, Leflunomide, PREMIER and TEMPO trials (n=1184) were pooled and the average SJC and CRP values from visits at 6, 9 and 12 months were determined. The two variables were then dichotomised into active and inactive, where inactive was defined as a mean. Radiographic outcomes were assessed according to these definitions. Results The greatest progression was seen in patients in whom both SJC and CRP were active and the smallest in those in whom both were inactive. If SJC was inactive, radiographic progression was not different between those with inactive or active CRP (0.7±4.3/year and 0.8±5.4/year, respectively, p=0.19). However, if CRP was inactive ( Conclusion In patients with RA who are near remission, the amount of joint swelling appears to be more predictive of radiographic progression than the amount of CRP.

Combination therapy for pain management in inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis)

Abstract: Background Despite optimal therapy with disease-modifying antirheumatic drugs, many people with inflammatory arthritis (IA) continue to have persistent pain that may require additional therapy. Objectives To assess the benefits and safety of combination pain therapy for people with IA (rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA) and other spondyloarthritis (SpA)). We planned to assess differences in effects between patients on background disease-modifying antirheumatic drug (DMARD) therapy and patients on no background therapy in subgroup analyses. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); MEDLINE; and EMBASE. We did not impose any date or language restrictions in the search. We also handsearched conference proceedings of the American College of Rheumatology and the European League against Rheumatism (2008-10). Selection criteria Randomised and controlled clinical trials (RCTs and CCTs) assessing combination therapy (at least two drugs from the following classes: analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, opioid-like drugs and neuromodulators (antidepressants, anticonvulsants and muscle relaxants)) compared with monotherapy, for adults with IA (RA, AS, PsA and other SpA). We speficically excluded studies that did not report pain or studies without a standardised pain scale as an outcome measure. Data collection and analysis Two review authors independently selected trials for inclusion, assessed risk of bias and extracted data. Main results Twenty-three trials (total of 912 patients) met the inclusion criteria (22 in RA; one in a mixed population of RA and osteoarthritis); all except one were published before 1990. Most study populations were not taking DMARDs (e.g. methotrexate, sulphasalazine, hydroxychloroquine and leflunomide) and all studies were performed prior to the introduction of biologic therapies (e.g. etanercept, infliximab and adalimumab). All trials were at high risk of bias, heterogeneity precluded meta-analysis, and we were only able to report a general description of results. The majority (18 studies, 78%) found no differences between the combination and monotherapy treatments they studied, while five (22%) reported conflicting results, favouring either the combination or monotherapy arms. From the 12 trials on NSAID + analgesic vs NSAID, nine reported no significant difference between the interventions, while three did: in two, the combination therapy achieved better pain control; and the third trial compared combination therapy with two different dosages of monotherapy (NSAID alone) and reported that a high dose phenylbutazone was superior to combination therapy (paracetamol + aspirin), which was superior to low dose phenylbutazone. From the five studies on the combination of two NSAIDS vs one NSAID, four reported no significant differences between interventions, and one reported significantly better pain control with combination therapy. The single trial comparing a combination of opioid + neuromodulator vs opioid reported better pain control with monotherapy. The remaining trials (NSAID + neuromodulator vs NSAID (3 trials); opioid + NSAID vs NSAID (1 trial); and opioid + analgesic vs analgesic (1 trial)) found no significant difference between combination therapy and monotherapy. Information regarding withdrawals due to inadequate analgesia and safety was incompletely reported, but in general there were no differences between combination therapy and monotherapy. No data were available that addressed the value of combination pain therapy or monotherapy for people with IA who have optimal disease suppression. There were no studies that included patients with AS, PsA or SpA. Authors' conclusions Based on 23 trials, all at high risk of bias, there is insufficient evidence to establish the value of combination therapy over monotherapy for people with IA. Importantly, there are no studies addressing the value of combination therapy for patients with IA who have persistent pain despite optimal disease suppression. Well designed trials are needed to address this question.

Monitoring rheumatoid arthritis.

Abstract: Purpose of review The approach to treating rheumatoid arthritis has changed over the last decade not only because of new therapeutic agents but also because of new treatment strategies. These strategies involve aiming at a treatment target, usually remission or low disease activity and monitoring patients regularly to attain this goal. Here we review the most recent insights related to monitoring of rheumatoid arthritis. Recent findings New insights were gained into the advantages and limitations of patient global assessment of disease severity and self-reported joint counts. The stringency of defining remission by the simplified disease activity index when compared with other instruments was confirmed by ultrasonography. Sensitivity to change and similarity to clinical assessments were shown for ultrasonographic indices; a simplified score for assessing joint damage by magnetic resonance imaging was presented. Physical function and working capacity continue to be impaired in the most recent decade. The evidence-based treat-to-target recommendations, developed by an international task force, are means to improve this situation. The American College of Rheumatology and the European League Against Rheumatism have most recently developed a stringent definition of remission for trials and practice. Summary The recent data provide compelling evidence for the importance of monitoring to attain the treatment targets in rheumatoid arthritis.

Diagnostic and prognostic value of antibodies and soluble biomarkers in undifferentiated peripheral inflammatory arthritis: a systematic review.

Abstract: Objective. When patients present with undifferentiated peripheral inflammatory arthritis (UPIA), early diagnosis and evaluation of prognostic factors are decisive steps for therapeutic success. We reviewed published evidence on the diagnostic and prognostic performance of autoantibodies and soluble biomarkers in UPIA. Methods. We conducted a systematic literature search covering studies published until January 2009. Additionally, we screened conference abstracts presented at European League Against Rheumatism and American College of Rheumatology meetings in 2007 and 2008. Results. We included 52 full-text articles and 12 abstracts. The association of anti-cyclic citrullinated peptide antibody (anti-CCP) and rheumatoid factor (RF) with diagnosis of rheumatoid arthritis at followup is compelling, supported by positive likelihood ratios (LR+) ranging between 1.2 and 20.5 for anti-CCP and 1.1 to 13.5 for RF. The same applies to radiographic outcome. For antikeratin antibodies (AKA) and antiperinuclear factor, existing evidence suggests diagnostic usefulness; AKA also showed prognostic value. Diagnostic and prognostic evidence for other autoantibodies and for bone and cartilage biomarkers was scarce, negative, or controversial. Conclusion. Among serological tests, unanimous evidence of substantial diagnostic value exists only for anti-CCP and RF, but is scarce for other markers.

Treating rheumatic patients with a malignancy

Abstract: Management of patients with inflammatory rheumatic disease and a history of (or even a current) malignant disease poses some particular challenges. As direct evidence of the risk of (recurrent or de novo) malignancy in patients with a history of malignant disease is scarce, such a risk may be estimated indirectly from the principal carcinogenicity of the respective drug to be used or (also indirectly) from cancer reactivation data from the transplant literature. In general, cancer risk is increased in patients receiving combination immunosuppressive treatment, but the risk in patients receiving individual drugs (with the exception of alkylating agents) remains entirely unclear. Indirect evidence supports the intuitive concept that the risk of cancer decreases over time after a successful cancer treatment. The only two studies in rheumatic patients with a cancer history were small and have not been able to show an increase in cancer reactivation. The risk of reactivation also depends on the site and location of the prior malignancy. In conclusion, the decision to treat a patient with a history of cancer immunosuppressively should be shared by the rheumatologist and the oncologist. Once the decision is established, such patients need intensive and close monitoring.

Algorithm for identification of undifferentiated peripheral inflammatory arthritis: a multinational collaboration through the 3e initiative

Abstract: To develop an algorithm for identification of undifferentiated peripheral inflammatory arthritis (UPIA).

Considering comorbidity in managing rheumatic diseases: going where trials cannot go.

Abstract: It remains a great challenge to treat the complexity of systemic rheumatic diseases in clinical practice. In contrast to what one may think, these challenges are not so much related to a lack of eff ective treatments, as many powerful drugs are available for treating rheumatoid arthritis, many of which became licensed over the course of the past decade [1]. Th e use of any of these new - as well as of the ‘older’ - drugs is scientifi cally based on results of randomized controlled trials. Th e classical design of these trials, however, is what makes the step into clinical practice so challenging. With the strict inclusion and exclusion criteria of these trials, the patient populations tested in those trials are in sharp contrast to patients requiring treatment in clinical practice. Th is is further supported by the fact that only a fraction of patients in a rheumatology practice would fulfi ll the criteria to enter phase II/III trials [2]. A central reason for this is that patients with potential risk factors for an adverse reaction to an investigative drug are excluded from the beginning to make the trial safer; but this group of patients constitutes a large portion of those who will ultimately require treatment in clinical practice. Until the recent calls for more pragmatic trials [3] that address patient populations with all the risk factors faced in daily practice have manifested in actual trial designs, physicians will often need to make their own decisions, weighing expected (but sometimes unknown) risks against the possible benefi ts. Although a number of management guidelines for