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1.
Artigo em Inglês | MEDLINE | ID: mdl-33523107

RESUMO

OBJECTIVES: To determine quantitative sacroiliac joint (SIJ) MRI lesion cut-offs that optimally define a positive MRI for inflammatory and structural lesions typical of axial spondyloarthritis (axSpA) and that predict clinical diagnosis. METHODS: The ASAS MRI group assessed MRIs from the ASAS Classification Cohort in two reading exercises: A. 169 cases and 7 central readers; B. 107 cases and 8 central readers. We calculated sensitivity/specificity for the number of SIJ quadrants or slices with bone marrow edema (BME), erosion, fat lesion, where a majority of central readers had high confidence there was a definite active or structural lesion. Cut-offs with ≥95% specificity were analyzed for their predictive utility for follow-up rheumatologist diagnosis of axSpA by calculating positive/negative predictive values (PPV/NPV) and selecting cut-offs with PPV≥95%. RESULTS: Active or structural lesions typical of axSpA on MRI had PPV≥95% for clinical diagnosis of axSpA. Cut-offs that best reflect definite active lesion typical of axSpA were either ≥4 SIJ quadrants with BME at any location or at the same location in ≥ 3 consecutive slices. For definite structural lesion, the optimal cut-offs were any one of ≥ 3 SIJ quadrants with erosion or ≥ 5 with fat lesion, erosion at the same location for ≥2 consecutive slices, fat lesion at the same location for ≥3 consecutive slices, or presence of a 'deep' (>1cm) fat lesion. CONCLUSION: We propose cut-offs for definite active and structural lesions typical of axSpA that have high PPV for a long-term clinical diagnosis of axSpA for application in disease classification and clinical research.

2.
RMD Open ; 7(1)2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33547228

RESUMO

OBJECTIVES: To investigate if inflammation detected by MRI or ultrasound at rheumatoid arthritis (RA) onset is predictive of erosive progression or poor response to methotrexate monotherapy, and to investigate if subclinical inflammation in remission is predictive of future treatment escalation or erosive progression. METHODS: In a 2-year study, 218 patients with disease-modifying antirheumatic drug-naïve early RA were treated by a tight-control treat-to-target strategy corresponding to current recommendations. MRI and ultrasound were performed at regular intervals. Baseline imaging-based inflammation measures were analysed as predictors for early methotrexate failure and erosive progression using univariate and multivariate regression adjusted for clinical, laboratory and radiographic measures. In patients in remission after 1 year, imaging measures were analysed as predictors of treatment escalation and erosive progression during the second year. The added value of imaging in prediction models was assessed using receiver operating characteristic analyses. RESULTS: Baseline MRI inflammation was associated with MRI erosive progression and ultrasound with radiographic erosive progression. No imaging inflammation measure was associated with early methotrexate failure. Imaging inflammation was present in a majority of patients in clinical remission. Tenosynovitis was associated with treatment escalation, and synovitis and tenosynovitis with MRI/radiographic erosive progression during the second year. Imaging information did not improve prediction models for any of the outcomes. CONCLUSIONS: Imaging-detected inflammation, both at diagnosis and in remission, is associated with elements of future disease development. However, the lack of a significant effect on prediction models indicates limited value of systematic MRI and ultrasound in management of early RA.

4.
Arthritis Rheumatol ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33538097

RESUMO

AIM: To investigate whether TNF inhibitors (TNFi) impact spinal radiographic progression in patients with axial spondyloarthritis (axSpA) and whether this is coupled to their effect on inflammation. METHODS: Patients with axSpA fulfilling the modified New York criteria were included in this prospective cohort (ALBERTA FORCAST). Spine radiographs, done every 2 years up to 10 years, were scored by 2 central readers, using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The indirect effect of TNFi on mSASSS was evaluated with generalized estimating equations by testing the interaction between TNFi and ASDAS at the start of each 2-year interval (t). If significant, the association between ASDAS at t and mSASSS at the end of the interval (t+1) was assessed in: i. patients treated with TNFi in all visits; ii. some visits and iii. never treated. In addition, the association between TNFi at t and mSASSS at t+1 (adjusting for ASDAS at t) was also tested (direct effect). RESULTS: In total, 314 patients were included. A gradient was seen for the effect of ASDAS at t on mSASSS at t+1 (interaction p-value 0.10), with a higher progression in patients never treated with TNFi [ß (95% CI): 0.41 (0.13; 0.68)] compared to those continuously treated [0.16 (0.00;0.31)] (indirect effect). However, TNFi also directly slowed progression as treated patients had on average 0.85 mSASSS-units less on t+1 compared to those not treated [-0.85 (-1.35; -0.35)]. CONCLUSION: TNFi reduce spinal radiographic progression in patients with radiographic axSpA which might be partially uncoupled from their effects on ASDAS inflammation.

5.
J Rheumatol ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33589554

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with active ankylosing spondylitis (AS). METHODS: This phase III, multicenter, double-blind, placebo-controlled study (NCT01583374) randomized patients with active AS (1:1:1) to placebo, apremilast 20 mg twice daily, or apremilast 30 mg twice daily for 24 weeks, followed by a long-term extension phase (up to 5 years). The primary endpoint was assessment of the SpondyloArthritis International Society 20 (ASAS 20) response at Week 16. The impact of treatment on radiographic outcomes after 104 weeks was assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). RESULTS: In total, 490 patients with active AS were randomized in the study (placebo: n=164; apremilast 20 mg twice daily: n=163; apremilast 30 mg twice daily: n=163). The primary endpoint of ASAS 20 response at Week 16 was not met (placebo: 37%; apremilast 20 mg twice daily: 35%; apremilast 30 mg twice daily: 33%; p=0.44 vs placebo). At Week 104, mean (SD) changes from baseline in mSASSS were 0.83 (3.6), 0.98 (2.2), and 0.57 (1.9) in patients initially randomized to placebo, apremilast 20 mg twice daily, and apremilast 30 mg twice daily, respectively. The most frequently reported adverse events through Week 104 were diarrhea, nasopharyngitis, upper respiratory infection, and nausea. CONCLUSION: No clinical benefit was observed with apremilast treatment in patients with active AS. The safety and tolerability of apremilast were consistent with its known profile.

6.
RMD Open ; 7(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33419871

RESUMO

OBJECTIVES: To summarise, by a systematic literature review (SLR), the evidence regarding pharmacological and non-pharmacological therapeutic strategies in difficult-to-treat rheumatoid arthritis (D2T RA), informing the EULAR recommendations for the management of D2T RA. METHODS: PubMed, Embase and Cochrane databases were searched up to December 2019. Relevant papers were selected and appraised. RESULTS: Two hundred seven (207) papers studied therapeutic strategies. Limited evidence was found on effective and safe disease-modifying antirheumatic drugs (DMARDs) in patients with comorbidities and other contraindications that limit DMARD options (patients with obesity, hepatitis B and C, risk of venous thromboembolisms, pregnancy and lactation). In patients who previously failed biological (b-)DMARDs, all currently used b/targeted synthetic (ts-)DMARDs were found to be more effective than placebo. In patients who previously failed a tumour necrosis factor inhibitor (TNFi), there was a tendency of non-TNFi bDMARDs to be more effective than TNFis. Generally, effectiveness decreased in patients who previously failed a higher number of bDMARDs. Additionally, exercise, psychological, educational and self-management interventions were found to improve non-inflammatory complaints (mainly functional disability, pain, fatigue), education to improve goal setting, and self-management programmes, educational and psychological interventions to improve self-management.The identified evidence had several limitations: (1) no studies were found in patients with D2T RA specifically, (2) heterogeneous outcome criteria were used and (3) most studies had a moderate or high risk of bias. CONCLUSIONS: This SLR underscores the scarcity of high-quality evidence on the pharmacological and non-pharmacological treatment of patients with D2T RA. Effectiveness of b/tsDMARDs decreased in RA patients who had failed a higher number of bDMARDs and a subsequent b/tsDMARD of a previously not targeted mechanism of action was somewhat more effective. Additionally, a beneficial effect of non-pharmacological interventions was found for improvement of non-inflammatory complaints, goal setting and self-management.

7.
Ann Rheum Dis ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33504485

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of the Janus kinase-1-preferential inhibitor filgotinib versus placebo or tumour necrosis factor-α inhibitor therapy in patients with active rheumatoid arthritis (RA) despite ongoing treatment with methotrexate (MTX). METHODS: This 52-week, multicentre, double-blind, placebo-controlled and active-controlled phase III trial evaluated once-daily oral filgotinib in patients with RA randomised 3:3:2:3 to filgotinib 200 mg (FIL200) or filgotinib 100 mg (FIL100), subcutaneous adalimumab 40 mg biweekly, or placebo (through week 24), all with stable weekly background MTX. The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Additional efficacy outcomes were assessed sequentially. Safety was assessed from adverse events and laboratory abnormalities. RESULTS: The proportion of patients (n=1755 randomised and treated) achieving ACR20 at week 12 was significantly higher for FIL200 (76.6%) and FIL100 (69.8%) versus placebo (49.9%; treatment difference (95% CI), 26.7% (20.6% to 32.8%) and 19.9% (13.6% to 26.2%), respectively; both p<0.001). Filgotinib was superior to placebo in key secondary endpoints assessing RA signs and symptoms, physical function and structural damage. FIL200 was non-inferior to adalimumab in terms of Disease Activity Score in 28 joints with C reactive protein ≤3.2 at week 12 (p<0.001); FIL100 did not achieve non-inferiority. Adverse events and laboratory abnormalities were comparable among active treatment arms. CONCLUSIONS: Filgotinib improved RA signs and symptoms, improved physical function, inhibited radiographic progression and was well tolerated in patients with RA with inadequate response to MTX. FIL200 was non-inferior to adalimumab. TRIAL REGISTRATION NUMBER: NCT02889796.

8.
Arthritis Res Ther ; 23(1): 43, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514428

RESUMO

BACKGROUND: Limited information is available on the impact of treatment with a tumor necrosis factor inhibitor (TNFi) on structural lesions in patients with recent-onset axial spondyloarthritis (axSpA). We compared 2-year structural lesion changes on magnetic resonance imaging (MRI) in the sacroiliac joints (SIJ) of patients with recent-onset axSpA receiving etanercept in a clinical trial (EMBARK) to similar patients not receiving biologics in a cohort study (DESIR). We also evaluated the relationship between the Ankylosing Spondylitis Disease Activity Score (ASDAS) and change in MRI structural parameters. METHODS: The difference between etanercept (EMBARK) and control (DESIR) in the net percentage of patients with structural lesion change was determined using the SpondyloArthritis Research Consortium of Canada SIJ Structural Score, with and without adjustment for baseline covariates. The relationship between sustained ASDAS inactive disease, defined as the presence of ASDAS < 1.3 for at least 2 consecutive time points 6 months apart, and structural lesion change was evaluated. RESULTS: This study included 163 patients from the EMBARK trial and 76 from DESIR. The net percentage of patients with erosion decrease was significantly greater for etanercept vs control: unadjusted: 23.9% vs 5.3%; P = 0.01, adjusted: 23.1% vs 2.9%; P = 0.01. For the patients attaining sustained ASDAS inactive disease on etanercept, erosion decrease was evident in significantly more than erosion increase: 34/104 (32.7%) vs 5/104 (4.8%); P < 0.001. A higher proportion had erosion decrease and backfill increase than patients in other ASDAS status categories. However, the trend across ASDAS categories was not significant and decrease in erosion was observed even in patients without a sustained ASDAS response. CONCLUSIONS: These data show that a greater proportion of patients achieved regression of erosion with versus without etanercept. However, the link between achieving sustained ASDAS inactive disease and structural lesion change on MRI could not be clearly established. TRIAL REGISTRATION: EMBARK: ClinicalTrials.gov identifier: NCT01258738 , Registered 13 December 2010; DESIR: ClinicalTrials.gov identifier: NCT01648907 , Registered 24 July 2012.

9.
Ann Rheum Dis ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33483318

RESUMO

OBJECTIVE: To produce European League Against Rheumatism (EULAR) recommendations for the reporting of ultrasound studies in rheumatic and musculoskeletal diseases (RMDs). METHODS: Based on the literature reviews and expert opinion (through Delphi surveys), a taskforce of 23 members (12 experts in ultrasound in RMDs, 9 in methodology and biostatistics together with a patient research partner and a health professional in rheumatology) developed a checklist of items to be reported in every RMD study using ultrasound. This checklist was further refined by involving a panel of 79 external experts (musculoskeletal imaging experts, methodologists, journal editors), who evaluated its comprehensibility, feasibility and comprehensiveness. Agreement on each proposed item was assessed with an 11-point Likert scale, grading from 0 (total disagreement) to 10 (full agreement). RESULTS: Two face-to-face meetings, as well as two Delphi rounds of voting, resulted in a final checklist of 23 items, including a glossary of terminology. Twenty-one of these were considered 'mandatory' items to be reported in every study (such as blinding, development of scoring systems, definition of target pathologies) and 2 'optional' to be reported only if applicable, such as possible confounding factors (ie, ambient conditions) or experience of the sonographers. CONCLUSION: An EULAR taskforce developed a checklist to ensure transparent and comprehensive reporting of aspects concerning research and procedures that need to be presented in studies using ultrasound in RMDs. This checklist, if widely adopted by authors and editors, will greatly improve the interpretability of study development and results, including the assessment of validity, generalisability and applicability.

10.
Ann Rheum Dis ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33452004

RESUMO

OBJECTIVES: To investigate efficacy and safety of the Janus kinase-1 inhibitor filgotinib in patients with active rheumatoid arthritis (RA) with limited or no prior methotrexate (MTX) exposure. METHODS: This 52-week, phase 3, multicentre, double-blind clinical trial (NCT02886728) evaluated once-daily oral filgotinib in 1252 patients with RA randomised 2:1:1:2 to filgotinib 200 mg with MTX (FIL200 +MTX), filgotinib 100 mg with MTX (FIL100 +MTX), filgotinib 200 mg monotherapy (FIL200), or MTX. The primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 24. RESULTS: The primary endpoint was achieved by 81% of patients receiving FIL200+ MTX versus 71% receiving MTX (p<0.001). A significantly greater proportion treated with FIL100+ MTX compared with MTX achieved an ACR20 response (80%, p=0.017) at week 24. Significant improvement in Health Assessment Questionnaire-Disability Index was seen at week 24; least-squares mean change from baseline was -1.0 and -0.94 with FIL200+MTX and FIL100+MTX, respectively, versus -0.81 with MTX (p<0.001, p=0.008, respectively). Significantly higher proportions receiving FIL200+MTX (54%) and FIL100+MTX (43%) achieved DAS28(CRP) <2.6 versus MTX (29%) (p<0.001 for both) at week 24. Hierarchical testing stopped for comparison of ACR20 for FIL200 monotherapy (78%) versus MTX (71%) at week 24 (p=0.058). Adverse event rates through week 52 were comparable between all treatments. CONCLUSIONS: FIL200+MTX and FIL100+MTX both significantly improved signs and symptoms and physical function in patients with active RA and limited or no prior MTX exposure; FIL200 monotherapy did not have a superior ACR20 response rate versus MTX. Filgotinib was well tolerated, with acceptable safety compared with MTX.

11.
RMD Open ; 7(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33514671

RESUMO

OBJECTIVES: To summarise the evidence on diagnostic issues in difficult-to-treat rheumatoid arthritis (D2T RA) informing the EULAR recommendations for the management of D2T RA. METHODS: A systematic literature review (SLR) was performed regarding the optimal confirmation of a diagnosis of rheumatoid arthritis (RA) and of mimicking diseases and the assessment of inflammatory disease activity. PubMed and Embase databases were searched up to December 2019. Relevant papers were selected and appraised. RESULTS: Eighty-two papers were selected for detailed assessment. The identified evidence had several limitations: (1) no studies were found including D2T RA patients specifically, and only the minority of studies included RA patients in whom there was explicit doubt about the diagnosis of RA or presence of inflammatory activity; (2) mostly only correlations were reported, not directly useful to evaluate the accuracy of detecting inflammatory activity in clinical practice; (3) heterogeneous, and often suboptimal, reference standards were used and (4) (thus) only very few studies had a low risk of bias.To ascertain a diagnosis of RA or relevant mimicking disease, no diagnostic test with sufficient validity and accuracy was identified. To ascertain inflammatory activity in patients with RA in general and in those with obesity and fibromyalgia, ultrasonography (US) was studied most extensively and was found to be the most promising diagnostic test. CONCLUSIONS: This SLR highlights the scarcity of high-quality studies regarding diagnostic issues in D2T RA. No diagnostic tests with sufficient validity and accuracy were found to confirm nor exclude the diagnosis of RA nor its mimicking diseases in D2T RA patients. Despite the lack of high-quality direct evidence, US may have an additional value to assess the presence of inflammatory activity in D2T RA patients, including those with concomitant obesity or fibromyalgia.

12.
RMD Open ; 7(1)2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33462157

RESUMO

OBJECTIVES: To characterise peripheral musculoskeletal involvement in patients with spondyloarthritis (SpA) including psoriatic arthritis (PsA), across the world. METHODS: Cross-sectional study with 24 participating countries. Patients with a diagnosis of axial SpA (axSpA), peripheral SpA (pSpA) or PsA according to their rheumatologist were included. The investigators were asked which diagnosis out of a list of six (axSpA, PsA, pSpA, inflammatory bowel disease-associated SpA, reactive arthritis or juvenile SpA (Juv-SpA)) fitted the patient best. Peripheral manifestations (ie, peripheral joint disease, enthesitis, dactylitis and root joint disease), their localisation and treatments were evaluated. RESULTS: A total of 4465 patients were included (61% men, mean age 44.5 years) from four geographic areas: Latin America (n=538), Europe plus North America (n=1677), Asia (n=975) and the Middle East plus North Africa (n=1275). Of those, 78% had ever suffered from at least one peripheral musculoskeletal manifestation; 57% had peripheral joint disease, 44% had enthesitis and 15% had dactylitis. Latin American had far more often peripheral joint disease (80%) than patients from other areas. Patients with PsA had predominantly upper limb and small joint involvement (52%).Hip and shoulder involvement was found in 34% of patients. The prevalence of enthesitis ranged between 41% in patients with axSpA and 65% in patients with Juv-SpA. Dactylitis was most frequent among patients with PsA (37%). CONCLUSION: These results suggest that all peripheral features can be found in all subtypes of SpA, and that differences are quantitative rather than qualitative. In a high proportion of patients, axial and peripheral manifestations coincided. These findings reconfirm SpA clinical subtypes are descendants of the same underlying disease, called SpA.

13.
J Rheumatol ; 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33262296

RESUMO

We compliment Bakirci, et al for their article1 on the prevalence of ultrasound (US) elementary lesions at mainly lower extremity enthesis sites in 80 (50 female, 30 male) healthy adults (20-80+ yrs) and their analyses of contributory factors. We also compliment the accompanying editorial by Hánová, et al 2 The core set of US enthesitis elementary lesions defined by the Outcomes in Rheumatology (OMERACT) group3 were analyzed in the following categories: (1) inflammation (hypoechogenicity and/or increased thickening of the tendon insertion, and power Doppler activity); (2) damage (enthesophytes, calcification, and erosions); and (3) total US scores, all within a 2-mm distance of the bone cortex1.

15.
RMD Open ; 6(3)2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33310864

RESUMO

OBJECTIVE: To investigate if in radiographic axial Spondyloarthritis (r-axSpA) low vertebral bone mineral density (BMD) is associated with development of new syndesmophytes at the same vertebral level. METHODS: In a post-hoc analysis from the ASSERT trial (infliximab vs placebo), dual-energy X-ray absorptiometry was used to measure baseline BMD (g/cm2) of the lumbar spine L1 to L4. Syndesmophyte formation was assessed in the same vertebrae on conventional radiographs defined as an increase in modified Stoke Ankylosing Spondylitis Spine Score from 0 or 1 to 2 or 3 after 2 years. Radiographs were scored by two readers. Generalised estimating equations (GEE) adjusted for within-patient correlation across multiple vertebrae, taking potential confounders into account. RESULTS: We analysed 599 vertebrae in 165 r-axSpA patients (78% male, mean (SD) age 38 (10) years, 67% with at least one syndesmophyte anywhere in the spine). In total, 24 to 74 new syndesmophytes developed in 9 (5%) to 30 (18%) patients and 13 (2%) to 39 (7%) vertebrae, if either a syndesmophyte was seen by both or only one of the readers (ie, specific and sensitive definitions) respectively. In multivariable analyses, no association was found between baseline local vertebral BMD and new syndesmophyte formation after 2 years: adjOR (95% CI): 0.56 (0.01, 44.45) (specific definition) and 0.26 (0.03, 2.63) (sensitive definition). CONCLUSION: In patients with active and established r-axSpA, with an observed low incidence of lumbar spine syndesmophyte formation over 2 years, no relationship was found between baseline BMD and new radiographic syndesmophyte formation at the same vertebra.

17.
RMD Open ; 6(3)2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33188136

RESUMO

OBJECTIVES: Review of efficacy and safety of Janus kinase (JAK) inhibition in immune-mediated inflammatory diseases (IMIDs). METHODS: A systematic literature research (SLR) of all publications on JAK inhibitors (JAKi) treatment published until March 2019 using MEDLINE, EMBASE and the Cochrane Library. Efficacy and safety were assessed in randomised controlled trials (RCTs), integrating long-term extension periods additionally for safety evaluation. RESULTS: 3454 abstracts were screened with 85 included in the final analysis (efficacy and RCT safety: n=72; safety only: n=13). Efficacy of RCTs investigating tofacitinib (TOFA, n=27), baricitinib (BARI, n=9), upadacitinib (UPA, n=14), filgotinib (FILGO, n=7), decernotinib (DEC, n=3) and peficitinib (PEF, n=7) was evaluated. Six head-to-head trials comparing JAKi with tumour necrosis factor inhibitors (TNFi) were included. Efficacy of JAKi was shown in rheumatoid arthritis (RA) for all agents, psoriatic arthritis (TOFA, FILGO), ankylosing spondylitis (TOFA, FILGO), systemic lupus erythematosus (BARI), chronic plaque psoriasis (TOFA, BARI, PEF), ulcerative colitis (TOFA, UPA), Crohn's disease (UPA, FILGO) and atopic dermatitis (TOFA, BARI, UPA). Safety analysis of 72 RCTs, one cohort study and 12 articles on long-term extension studies showed increased risks for infections, especially herpes zoster, serious infections and numerically higher rates of venous thromboembolic events. No increased malignancy rates or major adverse cardiac events were observed. CONCLUSION: JAKi provide good efficacy compared to placebo (and to TNFi in RA and Pso) across various IMIDs with an acceptable safety profile. This SLR informed the task force on points to consider for the treatment of IMIDs with JAKi with the available evidence.

18.
Ann Rheum Dis ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33158881

RESUMO

OBJECTIVES: Janus kinase inhibitors (JAKi) have been approved for use in various immune-mediated inflammatory diseases. With five agents licensed, it was timely to summarise the current understanding of JAKi use based on a systematic literature review (SLR) on efficacy and safety. METHODS: Existing data were evaluated by a steering committee and subsequently reviewed by a 29 person expert committee leading to the formulation of a consensus statement that may assist the clinicians, patients and other stakeholders once the decision is made to commence a JAKi. The committee included patients, rheumatologists, a gastroenterologist, a haematologist, a dermatologist, an infectious disease specialist and a health professional. The SLR informed the Task Force on controlled and open clinical trials, registry data, phase 4 trials and meta-analyses. In addition, approval of new compounds by, and warnings from regulators that were issued after the end of the SLR search date were taken into consideration. RESULTS: The Task Force agreed on and developed four general principles and a total of 26 points for consideration which were grouped into six areas addressing indications, treatment dose and comedication, contraindications, pretreatment screening and risks, laboratory and clinical follow-up examinations, and adverse events. Levels of evidence and strengths of recommendations were determined based on the SLR and levels of agreement were voted on for every point, reaching a range between 8.8 and 9.9 on a 10-point scale. CONCLUSION: The consensus provides an assessment of evidence for efficacy and safety of an important therapeutic class with guidance on issues of practical management.

19.
Ann Rheum Dis ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33144304

RESUMO

Rheumatic and musculoskeletal diseases (RMDs) form a diverse group of diseases. Proper disease assessment is pivotal, for instance to make treatment choices and for optimising outcome in general. RMDs are multidimensional diseases, entrenching many, sometimes very different aspects. Composite outcome measures ('composites') have become very popular to assess RMDs, because of their claim to catch all relevant dimensions of the disease into one convenient measure.In this article we discuss dimensionality of RMDs in the context of the most popular conceptual framework of RMDs, being an inflammatory process leading to some sort of damage over time. We will argue that multidimensionality not only refers to heterogeneity in disease manifestations, but also to heterogeneity in possible outcomes. Unlike most unidimensional measures, multidimensional composites may include several disease manifestations as well as several outcome dimensions into one index. We will discuss fundamental problems of multidimensional composites in light of modern strategies such as treat-to-target and personalised medicine.Finally, we will disentangle the use of multidimensional composites in clinical trials versus their use in clinical practice, and propose simple solutions in order to overcome problems of multidimensionality and to avoid harm to our patients due to overtreatment.

20.
Ann Rheum Dis ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004335

RESUMO

BACKGROUND: Despite treatment according to the current management recommendations, a significant proportion of patients with rheumatoid arthritis (RA) remain symptomatic. These patients can be considered to have 'difficult-to-treat RA'. However, uniform terminology and an appropriate definition are lacking. OBJECTIVE: The Task Force in charge of the "Development of EULAR recommendations for the comprehensive management of difficult-to-treat rheumatoid arthritis" aims to create recommendations for this underserved patient group. Herein, we present the definition of difficult-to-treat RA, as the first step. METHODS: The Steering Committee drafted a definition with suggested terminology based on an international survey among rheumatologists. This was discussed and amended by the Task Force, including rheumatologists, nurses, health professionals and patients, at a face-to-face meeting until sufficient agreement was reached (assessed through voting). RESULTS: The following three criteria were agreed by all Task Force members as mandatory elements of the definition of difficult-to-treat RA: (1) Treatment according to European League Against Rheumatism (EULAR) recommendation and failure of ≥2 biological disease-modifying antirheumatic drugs (DMARDs)/targeted synthetic DMARDs (with different mechanisms of action) after failing conventional synthetic DMARD therapy (unless contraindicated); (2) presence of at least one of the following: at least moderate disease activity; signs and/or symptoms suggestive of active disease; inability to taper glucocorticoid treatment; rapid radiographic progression; RA symptoms that are causing a reduction in quality of life; and (3) the management of signs and/or symptoms is perceived as problematic by the rheumatologist and/or the patient. CONCLUSIONS: The proposed EULAR definition for difficult-to-treat RA can be used in clinical practice, clinical trials and can form a basis for future research.

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