The impact of autoantibodies on the efficacy of biological disease-modifying anti-rheumatic drugs in rheumatoid arthritis: meta-analysis of randomized controlled trials.

OBJECTIVE: To investigate the efficacy of bDMARDs in patients with RA with RF/ACPA compared with patients without these autoantibodies. METHODS: Previous systematic literature reviews performed by EULAR RA management task forces were searched for qualifying RCTs. RCTs investigating the efficacy of bDMARDs and including both autoantibody-positive (≤80% of total population) and -negative RA patients were eligible. For trials comparing bDMARD+csDMARD vs csDMARD, relative risks (RR) comparing two groups (RF + vs RF-, ACPA+ vs ACPA-) were calculated for efficacy outcomes for each arm. Subsequently, relative risk ratios (RRRs) were computed, as the ratio of RR of the bDMARD-arm and the RR from the non-bDMARD-arm. Pooled effects were obtained with random effect meta-analyses. RESULTS: Data from 28 eligible RCTs were analyzed, pooling 23 studies in three subgroups: 6 including csDMARD-naïve patients, 14 csDMARD-IR, and 3 TNFi-IR patients. In csDMARD-naïve and csDMARD-IR patients, seropositivity was not associated with a better response to bDMARDs: pooled 6-month ACR20 RRRs 1.02 (0.88-1.18) and 1.09 (0.90-1.32), respectively. Other outcomes showed no difference between groups either. In TNFi-IR patients, based on 3 trials, the 6-month ACR20 RRR was 2.28 (1.31-3.95), favoring efficacy in seropositive patients. Other outcomes mostly showed no significant difference between the groups. Based on the mode of action, efficacy was comparable between RF-positive and RF-negative patients for both TNFi and non-TNFi treatment and also for the individual bDMARDs. CONCLUSION: The effect of bDMARDs is generally comparable in patients with and without RF/ACPA, regardless of the patient population, the mechanism of action or individual drug used.

Identification of a distinct imaging phenotype may improve the management of palindromic rheumatism.

OBJECTIVES: To use high-resolution imaging to characterise palindromic rheumatism (PR) and to compare the imaging pattern observed to that seen in new-onset rheumatoid arthritis (NORA). METHODS: Ultrasound (US) assessment of synovitis, tenosynovitis and non-synovial extracapsular inflammation (ECI) was performed during and between flares in a prospective treatment-naive PR cohort. MRI of the flaring region was performed where possible. For comparison, the same US assessment was also performed in anticyclic citrullinated peptide (CCP) positive individuals with musculoskeletal symptoms (CCP+ at risk) and patients with NORA. RESULTS: Thirty-one of 79 patients with PR recruited were assessed during a flare. A high frequency of ECI was identified on US; 19/31 (61%) of patients had ECI including 12/19 (63%) in whom ECI was identified in the absence of synovitis. Only 7/31 (23%) patients with PR had synovitis (greyscale ≥1 and power Doppler ≥1) during flare. In the hands/wrists, ECI was more prevalent in PR compared with NORA and CCP+ at risk (65% vs 29 % vs 6%, p<0.05). Furthermore, ECI without synovitis was specific for PR (42% PR vs 4% NORA (p=0.003) and 6% CCP+ at risk (p=0.0012)). Eleven PR flares were captured by MRI, which was more sensitive than US for synovitis and ECI. 8/31 (26%) patients with PR developed RA and had a similar US phenotype to NORA at progression. CONCLUSION: PR has a distinct US pattern characterised by reversible ECI, often without synovitis. In patients presenting with new joint swelling, US may refine management by distinguishing relapsing from persistent arthritis.

Validity of a two-component imaging-derived disease activity score for improved assessment of synovitis in early rheumatoid arthritis.

OBJECTIVES: Imaging of joint inflammation provides a standard against which to derive an updated DAS for RA. Our objectives were to develop and validate a DAS based on reweighting the DAS28 components to maximize association with US-assessed synovitis. METHODS: Early RA patients from two observational cohorts (n = 434 and n = 117) and a clinical trial (n = 59) were assessed at intervals up to 104 weeks from baseline; all US scans were within 1 week of clinical exam. There were 899, 163 and 183 visits in each cohort. Associations of combined US grey scale and power Doppler scores (GSPD) with 28 tender joint count and 28 swollen joint count (SJC28), CRP, ESR and general health visual analogue scale were examined in linear mixed model regressions. Cross-validation evaluated model predictive ability. Coefficients learned from training data defined a re-weighted DAS28 that was validated against radiographic progression in independent data (3037 observations; 717 patients). RESULTS: Of the conventional DAS28 components only SJC28 and CRP were associated with GSPD in all three development cohorts. A two-component model including SJC28 and CRP outperformed a four-component model (R2 = 0.235, 0.392, 0.380 vs 0.232, 0.380, 0.375, respectively). The re-weighted two-component DAS28CRP outperformed conventional DAS28 definitions in predicting GSPD (Δtest log-likelihood <-2.6, P < 0.01), Larsen score and presence of erosions. CONCLUSION: A score based on SJC28 and CRP alone demonstrated stronger associations with synovitis and radiographic progression than the original DAS28 and should be considered in research on pathophysiological manifestations of early RA. Implications for clinical management of RA remain to be established.

Genome-wide association study of response to methotrexate in early rheumatoid arthritis patients.

Methotrexate (MTX) monotherapy is a common first treatment for rheumatoid arthritis (RA), but many patients do not respond adequately. In order to identify genetic predictors of response, we have combined data from two consortia to carry out a genome-wide study of response to MTX in 1424 early RA patients of European ancestry. Clinical endpoints were change from baseline to 6 months after starting treatment in swollen 28-joint count, tender 28-joint count, C-reactive protein and the overall 3-component disease activity score (DAS28). No single nucleotide polymorphism (SNP) reached genome-wide statistical significance for any outcome measure. The strongest evidence for association was with rs168201 in NRG3 (p = 10-7 for change in DAS28). Some support was also seen for association with ZMIZ1, previously highlighted in a study of response to MTX in juvenile idiopathic arthritis. Follow-up in two smaller cohorts of 429 and 177 RA patients did not support these findings, although these cohorts were more heterogeneous.

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2016 update of the EULAR recommendations for management of rheumatoid arthritis.

OBJECTIVES: To assess the safety of synthetic (s) and biological (b) disease-modifying antirheumatic drugs (DMARDs) for the management of rheumatoid arthritis (RA) to inform the European League Against Rheumatism recommendations for the management of RA. METHODS: Systematic literature review (SLR) of observational studies comparing any DMARD with another intervention for the management of patients with RA. All safety outcomes were included. A comparator group was required for the study to be included. Risk of bias was assessed with the Hayden's tool. RESULTS: Twenty-six observational studies addressing diverse safety outcomes of therapy with bDMARDs met eligibility criteria (15 on serious infections, 4 on malignancies). Substantial heterogeneity precluded meta-analysis. Together with the evidence from the 2013 SLR, based on 15 studies, 7 at low risk of bias, patients on bDMARDs compared with patients on conventional sDMARDs had a higher risk of serious infections (adjusted HR (aHR) 1.1 to 1.8)-without differences across bDMARDs-a higher risk of tuberculosis (aHR 2.7 to 12.5), but no increased risk of infection by herpes zoster. Patients on bDMARDs did not have an increased risk of malignancies in general, lymphoma or non-melanoma skin cancer, but the risk of melanoma may be slightly increased (aHR 1.5). CONCLUSIONS: These findings confirm the known safety pattern of bDMARDs, including both tumour necrosis factor-α inhibitor (TNFi) and non-TNFi, for the treatment of RA.

Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2016 update of the EULAR recommendations for the management of rheumatoid arthritis.

OBJECTIVES: To update the evidence for the efficacy of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) to inform European League Against Rheumatism (EULAR) Task Force treatment recommendations. METHODS: MEDLINE, EMBASE and Cochrane databases were searched for phase III or IV (or phase II, if these studies were lacking) randomised controlled trials (RCTs) published between January 2013 and February 2016. Abstracts from the American College of Rheumatology and EULAR conferences were obtained. RESULTS: The RCTs confirmed greater efficacy with a bDMARD+conventional synthetic DMARD (csDMARD) versus a csDMARDs alone (level 1A evidence). Using a treat-to-target strategy approach, commencing and escalating csDMARD therapy and adding a bDMARD in cases of non-response, is an effective approach (1B). If a bDMARD had failed, improvements in clinical response were seen on switching to another bDMARD (1A), but no clear advantage was seen for switching to an agent with another mode of action. Maintenance of clinical response in patients in remission or low disease activity was best when continuing rather than stopping a bDMARD, but bDMARD dose reduction or 'spacing' was possible, with a substantial proportion of patients achieving bDMARD-free remission (2B). RCTs have also demonstrated efficacy of several new bDMARDs and biosimilar DMARDs (1B). CONCLUSIONS: This systematic literature review consistently confirmed the previously reported efficacy of bDMARDs in RA and provided additional information on bDMARD switching and dose reduction.

Rheumatoid arthritis management of early disease.

PURPOSE OF REVIEW: Early effective treatment has led to major improvements in patients with rheumatoid arthritis. This review aims to address the treatment of early rheumatoid arthritis, in particular the different therapeutic strategies evaluated in clinical trials to achieve optimal disease control. RECENT FINDINGS: The use of biological disease-modifying antirheumatic drugs (bDMARDs) has significantly improved patient outcomes. Overall, studies using bDMARD induction have shown early clinical improvements, with high proportions achieving remission with minimal radiographic progression. As these drugs are still relatively costly, conventional synthetic DMARDs, as monotherapy or in combination, remain the mainstay of treatment initiation. Good, albeit somewhat slower, responses can be achieved with these drugs. Strategies incorporating glucocorticoids and a treat-to-target approach (i.e. regular monitoring of disease activity and early treatment escalation with a conventional synthetic or b-DMARD, if needed) have shown additional benefit. In patients achieving low disease activity or remission, bDMARD dose reduction and withdrawal, and even drug-free remission have been possible in some. SUMMARY: In patients with early rheumatoid arthritis, conventional synthetic DMARDs and glucocorticoids used within a treat-to-target setting, and the addition of a bDMARD if required, outcomes have improved significantly. A proportion of patients are able to deescalate treatment after bDMARD therapy, with a significant minority achieving drug-free remission.

Ultrasound findings predict progression to inflammatory arthritis in anti-CCP antibody-positive patients without clinical synovitis.

OBJECTIVES: To determine whether ultrasound can identify anti-cyclic citrullinated peptide (anti-CCP) antibody-positive patients without clinical synovitis (CS) who progress to inflammatory arthritis (IA). METHODS: In a prospective study, anti-CCP-positive patients without CS underwent ultrasound imaging of 32 joints (wrists, metacarpophalangeal joints, proximal interphalangeal joints and metatarsophalangeal joints (MTPs)) and were monitored for the development of IA. Associations between baseline ultrasound findings (grey scale (GS), power Doppler (PD) and erosions) and (1) progression to IA and (2) development of CS within an individual joint were measured. RESULTS: Consecutive anti-CCP-positive patients (n=136; mean age 51 years, 100 women) were followed up for median of 18.3 months (range 0.1-79.6). At baseline 96% had GS, 30% had PD and 21% had one or more erosions. IA developed in 57 patients (42%) after median of 8.6 months (range 0.1-52.4). Ultrasound abnormalities (GS ≥2, PD ≥1 or erosion ≥1) were found in 86% at baseline compared with 67% of non-progressors (χ2=6.3, p=0.012). Progression to IA was significantly higher in those with ultrasound findings in any joint (excluding MTPs for GS) (GS ≥2: 55% vs 24%, HR (95% CI) 2.3 (1.0 to 4.9), p=0.038; PD ≥2: 75% vs 32%, 3.7 (2.0 to 6.9), p<0.001 and erosion ≥1: 71% vs 34%, 2.9 (1.7 to 5.1), p<0.001). Furthermore, progression occurred earlier with PD ≥2 (median 7.1 vs 52.4 months) and erosion ≥1 (15.4 vs 46.5). At the individual joint level, the trend for progression to CS was more significant for GS and PD (GS ≥2: 26% vs 3%, 9.4 (5.1 to 17.5), p<0.001; PD ≥2: 55% vs 4%, 31.3 (15.6 to 62.9), p<0.001). CONCLUSION: Ultrasound features of joint inflammation may be detected in anti-CCP-positive patients without CS. Ultrasound findings predict progression (and rate of progression) to IA, with the risk of progression highest in those with PD signal. TRIAL REGISTRATION NUMBER: NCT02012764; Results.

Efficacy of biological disease-modifying antirheumatic drugs: a systematic literature review informing the 2013 update of the EULAR recommendations for the management of rheumatoid arthritis.

OBJECTIVES: To update the evidence for the efficacy of biological disease-modifying antirheumatic drugs (bDMARD) in patients with rheumatoid arthritis (RA) to inform the European League Against Rheumatism(EULAR) Task Force treatment recommendations. METHODS: Medline, Embase and Cochrane databases were searched for articles published between January 2009 and February 2013 on infliximab, etanercept, adalimumab, certolizumab-pegol, golimumab, anakinra, abatacept, rituximab, tocilizumab and biosimilar DMARDs (bsDMARDs) in phase 3 development. Abstracts from 2011 to 2012 American College of Rheumatology (ACR) and 2011-2013 EULAR conferences were obtained. RESULTS: Fifty-one full papers, and 57 abstracts were identified. The randomised controlled trials (RCT) confirmed the efficacy of bDMARD+conventional synthetic DMARDs (csDMARDs) versus csDMARDs alone (level 1B evidence). There was some additional evidence for the use of bDMARD monotherapy, however bDMARD and MTX combination therapy for all bDMARD classes was more efficacious (1B). Clinical and radiographic responses were high with treat-to-target strategies. Earlier improvement in signs and symptoms were seen with more intensive initial treatment strategies, but outcomes were similar upon addition of bDMARDs in patients with insufficient response to MTX. In general, radiographic progression was lower with bDMARD use, mainly due to initial treatment effects. Although patients may achieve bDMARD- and drug-free remission, maintenance of clinical responses was higher with bDMARD continuation (1B), but bDMARD dose reduction could be applied (1B). There was still no RCT data for bDMARD switching. CONCLUSIONS: The systematic literature review confirms efficacy of biological DMARDs in RA. It addresses different treatment strategies with the potential for reduction in therapy, particularly with early disease control, and highlights emerging therapies.

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis.

OBJECTIVES: To update the evidence for the safety of synthetic disease-modifying antirheumatic drugs (sDMARDs), glucocorticoids (GC) and biological DMARDs (bDMARDs) in patients with rheumatoid arthritis (RA) to inform the European League Against Rheumatism (EULAR) recommendations for the management of RA. METHODS: Systematic literature review (SLR) of observational studies (including registries). Interventions were any bDMARD (anakinra, infliximab, etanercept, adalimumab, rituximab, abatacept, tocilizumab, golimumab or certolizumab pegol) or sDMARD (methotrexate, leflunomide, hydroxychloroquine, sulfasalazine, gold/auranofin, azathioprine, chlorambucil, chloroquine, cyclosporin, cyclophosphamide, mycophenolate, minocycline, penicillamine, tacrolimus or tofacitinib) and a comparator was required. Information on GCs was collected from the included studies. All safety outcomes were included. RESULTS: Forty-nine observational studies addressing diverse safety outcomes of therapy with bDMARDs met eligibility criteria. Substantial heterogeneity precluded meta-analysis of any of the outcomes. Patients on tumour necrosis factor inhibitors (TNFi) compared to patients on conventional sDMARDs had a higher risk of serious infections (adjusted HR (aHR) 1.1-1.8), a higher risk of tuberculosis, and an increased risk of infection by herpes zoster cannot be excluded. Patients on TNFi did not have an increased risk for malignancies in general, lymphoma or non-melanoma skin cancer, but the risk of melanoma may be slightly increased (aHR 1.5). From the studies identified on conventional sDMARDs, no new safety signals were found. CONCLUSIONS: The findings from this SLR confirm the known safety pattern of sDMARDs and bDMARDs for the treatment of RA.

A systematic literature review of strategies promoting early referral and reducing delays in the diagnosis and management of inflammatory arthritis.

BACKGROUND: Despite the importance of timely management of patients with inflammatory arthritis (IA), delays exist in its diagnosis and treatment. OBJECTIVE: To perform a systematic literature review to identify strategies addressing these delays to inform an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) taskforce. METHODS: The authors searched literature published between January 1985 and November 2010, and ACR and EULAR abstracts between 2007-2010. Additional information was obtained through a grey literature search, a survey conducted through ACR and EULAR, and a hand search of the literature. RESULTS: (1) From symptom onset to primary care, community case-finding strategies, including the use of a questionnaire and autoantibody testing, have been designed to identify patients with early IA. Several websites provided information on IA but were of varying quality and insufficient to aid early referral. (2) At a primary care level, education programmes and patient self-administered questionnaires identified patients with potential IA for referral to rheumatology. Many guidelines emphasised the need for early referral with one providing specific referral criteria. (3) Once referred, early arthritis clinics provided a point of early access for rheumatology assessment. Triage systems, including triage clinics, helped prioritise clinic appointments for patients with IA. Use of referral forms standardised information required, further optimising the triage process. Wait times for patients with acute IA were also reduced with development of rapid access systems. CONCLUSIONS: This review identified three main areas of delay to care for patients with IA and potential solutions for each. A co-ordinated effort will be required by the rheumatology and primary care community to address these effectively.

A systematic literature review of strategies promoting early referral and reducing delays in the diagnosis and management of inflammatory arthritis.

BACKGROUND: Despite the importance of timely management of patients with inflammatory arthritis (IA), delays exist in its diagnosis and treatment. OBJECTIVE: To perform a systematic literature review to identify strategies addressing these delays to inform an American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) taskforce. METHODS: The authors searched literature published between January 1985 and November 2010, and ACR and EULAR abstracts between 2007-2010. Additional information was obtained through a grey literature search, a survey conducted through ACR and EULAR, and a hand search of the literature. RESULTS: (1) From symptom onset to primary care, community case-finding strategies, including the use of a questionnaire and autoantibody testing, have been designed to identify patients with early IA. Several websites provided information on IA but were of varying quality and insufficient to aid early referral. (2) At a primary care level, education programmes and patient self-administered questionnaires identified patients with potential IA for referral to rheumatology. Many guidelines emphasised the need for early referral with one providing specific referral criteria. (3) Once referred, early arthritis clinics provided a point of early access for rheumatology assessment. Triage systems, including triage clinics, helped prioritise clinic appointments for patients with IA. Use of referral forms standardised information required, further optimising the triage process. Wait times for patients with acute IA were also reduced with development of rapid access systems. CONCLUSIONS: This review identified three main areas of delay to care for patients with IA and potential solutions for each. A co-ordinated effort will be required by the rheumatology and primary care community to address these effectively.

Prevalence of Periodontal Disease and Periodontopathic Bacteria in Anti-Cyclic Citrullinated Protein Antibody-Positive At-Risk Adults Without Arthritis.

Importance: The prevalence of periodontitis is increased in patients with rheumatoid arthritis (RA) and periodontopathic bacteria can citrullinate proteins. Periodontitis may, therefore, be an initiator of RA and a target for prevention. Periodontal disease and periodontal bacteria have not been investigated in at-risk individuals with RA autoimmunity but no arthritis. Objective: To examine periodontal disease and periodontopathic bacteria in anti-cyclic citrullinated protein (anti-CCP) antibody-positive at-risk individuals without arthritis. Design, Setting, and Participants: This cross-sectional study took place at a teaching hospital from April 27, 2015, to May 8, 2017. Forty-eight anti-CCP-positive individuals without arthritis (CCP+ at-risk) were recruited nationally. Twenty-six patients with early RA (ERA) and 32 healthy control individuals were recruited locally. Data were analyzed between June 1, 2017, and December 1, 2017. Interventions: Periodontal assessment and examination of joints using ultrasonography. Main Outcomes and Measures: Prevalence of diseased periodontal sites, clinical periodontitis, and periodontal inflamed surface area in CCP+ at-risk individuals compared with patients with ERA and healthy individuals matched for age and smoking. Paired-end sequencing of DNA from subgingival plaque from diseased and healthy periodontal sites was performed and DNA was profiled and analyzed. Results: A total of 48 CCP+ at-risk individuals (mean [SD] age, 51.9 [11.4] years; 31 [65%] female), 26 patients with ERA (mean [SD] age, 54.4 [16.7] years; 14 [54%] female), and 32 healthy individuals (mean [SD] age, 49.4 [15.3] years; 19 [59%] female) were recruited. Of 48 CCP+ at-risk individuals, 46 had no joint inflammation on ultrasonography. Thirty-five CCP+ at-risk individuals (73%), 12 healthy individuals (38%), and 14 patients with ERA (54%) had clinical periodontitis. The median (interquartile range) percentage of periodontal sites with disease was greater in CCP+ at-risk individuals compared with healthy individuals (3.3% [0%-11.3%] vs 0% [0%-0.7%]) and similar to patients with ERA (1.1% [0%-13.1%]). Median (interquartile range) periodontal inflamed surface area was higher in CCP+ at-risk individuals compared with healthy individuals (221 mm2 [81-504 mm2] vs 40 mm2 [12-205 mm2]). Patients with CCP+ at-risk had increased relative abundance of Porphyromonas gingivalis (but not Aggregatibacter actinomycetemcomitans) at healthy periodontal sites compared with healthy individuals (effect size, 3.00; 95% CI, 1.71-4.29) and patients with ERA (effect size, 2.14; 95% CI, 0.77-3.52). Conclusions and Relevance: This study found increased prevalence of periodontitis and P gingivalis in CCP+ at-risk individuals. This suggests periodontitis and P gingivalis are associated with disease initiation and could be targets for preventive interventions in RA.

Comorbidities in Anti-Cyclic Citrullinated Peptide Positive At-Risk Individuals Do Not Differ from Those Patients with Early Inflammatory Arthritis.

OBJECTIVES: To compare comorbidities in a cohort of cyclic citrullinated peptide (CCP) antibody positive patients without or prior to onset of inflammatory arthritis (IA) to those in patients with early IA. METHODS: Baseline data from two established cohorts were used. The first recruited people at risk of IA: CCP antibody positive cases without IA (CCP Cohort, n = 296). The second cohort [the Inflammatory Arthritis CONtinuum study (IACON)] recruited patients with early IA (n = 725). Proportions of patients with given comorbidities were compared between cohorts and then logistic regression was used to determine odds ratios (OR) for the CCP cohort having specific comorbidities, compared to IACON patients. Analyses adjusted for gender, age, smoking status, and body mass index. RESULTS: Patients from the CCP cohort were younger (mean age 50, compared to 53 years). The proportion of patients with at least one comorbidity was higher in the IACON than the CCP cohort: (40% compared to 24%, respectively). Results of logistic regression analyses suggested the odds of hypertension, taking a lipid-lowering agent, ischemic heart disease, cerebrovascular disease, lung disease, and diabetes were not increased in either cohort. However, patients in the CCP cohort were more likely to be taking an antidepressant (OR = 1.62, 95% CI 1.03, 2.56, p = 0.037). CONCLUSION: There was no significant difference in comorbidities among people with CCP antibodies but without IA, compared to those of patients with established IA.

Role of ultrasound imaging in individuals at risk of RA.

Early diagnosis and treatment improves outcomes for patients with rheumatoid arthritis (RA). Studies have shown that musculoskeletal ultrasound is more sensitive than clinical examination in identifying synovitis. This review aims to address the role of ultrasound in identifying (1) patients with early inflammatory arthritis (IA) at risk of progression to RA and (2) those without clinical synovitis at risk of progression to early IA and therefore early RA.

Biologics in rheumatoid arthritis: where are we going?

Biological disease-modifying antirheumatic drugs have significantly improved outcomes for patients with rheumatoid arthritis, but cost limits their use. This article assesses data on patients who have achieved remission or low disease activity with these drugs and the possibility of dose reduction or discontinuation in these patients.

Is there subclinical synovitis in early psoriatic arthritis? A clinical comparison with gray-scale and power Doppler ultrasound.

OBJECTIVE: Arthritis activity assessments in psoriatic arthritis (PsA) have traditionally relied on tender and swollen joint counts, but in rheumatoid arthritis, multiple studies have demonstrated subclinical inflammation using modern imaging. The aim of this study was to compare clinical examination and ultrasound (US) findings in an early PsA cohort. METHODS: Forty-nine disease-modifying antirheumatic drug-naive patients with recent-onset PsA (median disease duration 10 months) underwent gray-scale (GS) and power Doppler (PD) US of 40 joints plus tender and swollen joint counts of 68/66 joints. GS and PD were scored on a 0-3 semiquantitative scale for each joint. Clinically active joints were defined as tender and/or swollen and US active joints were defined as a GS score ≥2 and/or a PD score ≥1. RESULTS: The most common sites for subclinical synovitis were the wrist (30.6%), knee (21.4%), metatarsophalangeal (MTP) joints (26.5-33.7%), and metacarpophalangeal joints (10.2-19.4%). Excluding MTP joints and ankles, 37 (75.5%) of 49 patients had subclinical synovitis with a median of 3 (interquartile range [IQR] 1-4) joints involved. In contrast, clinical overestimation of synovitis occurred most commonly at the shoulder (38%) and ankle (28.6%). Twelve of 49 patients were classified clinically as having oligoarthritis; of these, subclinical synovitis identified 8 (75%) as having polyarthritis with an increase in their median joint count from 3 (IQR 1-4) to 6 (IQR 5-7). CONCLUSION: This study has demonstrated that subclinical synovitis, as identified by US, is very common in early PsA and led to the majority of oligoarthritis patients being reclassified as having polyarthritis. Further research is required into the relationship of such subclinical synovitis to structural progression.

Is there a place for initial treatment with biological DMARDs in the early phase of RA?

The use of biological disease-modifying antirheumatic drugs (bDMARDs) has changed the face of rheumatoid arthritis (RA). Achieving remission, normal function and prevention of joint damage are now possible for many patients with RA. In clinical practice, however, particularly with cost considerations, bDMARDs are usually prescribed after failure of one or more conventional synthetic DMARDs. With evidence that early treatment has a greater impact than later on, the question regarding initial bDMARD therapy and their potential role within a window of opportunity to influence disease outcomes remain. The increasing emphasis on early diagnosis and research into the preclinical phase of the disease also heralds the question, 'Can bDMARDs prevent the development of RA?' The aim of this review is to review randomised controlled trials with bDMARDs as initial therapy in early RA and to discuss their role in early disease.