Tenderness and radiographic progression in rheumatoid arthritis and psoriatic arthritis.

OBJECTIVE: The aim of this study was to assess the predictive value of tenderness in the absence of swelling with consideration of other potential risk factors for subsequent radiographic progression in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: Clinical and sonographic (grey scale and power Doppler (PD)) examination of 22 joints of the hand were performed in patients with RA and PsA. The impact of tenderness on progression after 2 years was analysed in non-swollen joints for RA and PsA separately with multilevel mixed logistic regression analysis. RESULTS: We included 1207 joints in 55 patients with RA and 352 joints in 18 patients with PsA. In RA, tenderness was associated with radiographic progression after 2 years (model 2: OR 1.85 (95% CI 1.01 to 3.27), p=0.047), although the association of PD (OR 2.92 (95% CI 1.71 to 5.00), p<0.001) and erosions (OR 4.74 (95% CI 2.44 to 9.23), p<0.001) with subsequent structural damage was stronger. In PsA, we found a positive but not significant association between tenderness and radiographic progression (OR 1.72 (95% CI 0.71 to 4.17), p=0.23). In contrast, similarly to RA, erosions (OR 4.62 (95% CI 1.29 to 16.54), p=0.019) and PD (OR 3.30 (95% CI 1.13 to 9.53), p=0.029) had a marked effect on subsequent structural damage. CONCLUSION: Our findings imply that tenderness in non-swollen joints in RA is associated with subsequent damage. In both diseases, additional risk factors, such as sonographic signs for synovitis and baseline radiographic damage are associated with radiographic progression.

Tocilizumab in patients with new onset polymyalgia rheumatica (PMR-SPARE): a phase 2/3 randomised controlled trial.

BACKGROUND: Polymyalgia rheumatica is the second most common inflammatory rheumatic disease of people >50 years. Glucocorticoid therapy is highly effective, but many patients require treatment for several years. Effective glucocorticoid sparing agents are still needed. METHODS: In this double-blind, multi-centre phase 2/3 clinical trial, we randomly assigned 36 patients with new onset polymyalgia rheumatica from three centres to receive subcutaneous tocilizumab (162 mg per week) or placebo for 16 weeks (1:1 ratio). All patients received oral prednisone, tapered from 20 mg to 0 mg over 11 weeks.The primary endpoint was the proportion of patients in glucocorticoid-free remission at week 16; key secondary endpoints, including time to first relapse and cumulative glucocorticoid dose at weeks 16 and 24, were evaluated. RESULTS: From 20 November 2017 to 28 October 2019 39 patients were screened for eligibility; 19 patients received tocilizumab and 17 placebo. Glucocorticoid-free remission at week 16 was achieved in 12 out of 19 patients on tocilizumab (63.2%) and 2 out of 17 patients receiving placebo (11.8%, p=0.002), corresponding to an OR of 12.9 (95 % CI: 2.2 to 73.6) in favour of tocilizumab. Mean (±SD) time to first relapse was 130±13 and 82±11 days (p=0.007), respectively, and the median (IQR) cumulative glucocorticoid dose was 727 (721-842) mg and 935 (861-1244) mg (p=0.003), respectively. Serious adverse events were observed in five placebo patients and one tocilizumab patient. CONCLUSION: In patients with new onset polymyalgia rheumatica undergoing rapid glucocorticoid tapering, tocilizumab was superior to placebo regarding sustained glucocorticoid-free remission, time to relapse and cumulative glucocorticoid dose. TRIAL REGISTRATION NUMBER: NCT03263715.

Torque Teno Virus quantification for monitoring of immunomodulation with biologic compounds in the treatment of rheumatoid arthritis.

OBJECTIVES: RA patients who fail to respond to MTX can receive biologic dMARDs (bDMARDs). The Torque Teno Virus (TTV) is a potential novel candidate for monitoring of immunosuppression. We explore TTV in these patients and its association with clinical response to bDMARDs. METHODS: The BioBio Study is a multicentre randomized open-label trial, including RA patients with insufficient response to MTX. Patients were randomized to either TNFi (infliximab, INF), anti-IL-6 (tocilizumab, TCZ), CTLA4-Ig (abatacept, ABA) or anti-CD20 (rituximab, RTX) in addition to MTX. PCR was used to quantify TTV in the peripheral blood. RESULTS: TTV was measured in 95 patients (INF, n = 23; TCZ, n = 22; ABA, n = 27; RTX; n = 23). TTV increased by a median of 4.5 × 104 copies/ml [c/ml; interquartile range (IQR) 0-7.5 × 105] after 3 months. TTV levels at month 3 were associated with the Simplified Disease Activity Index (SDAI) (P = 0.03) and the Clinical Disease Activity Index (CDAI) response (P = 0.026) at month 6. A TTV cut-off level of 1.2 × 106 c/ml at month 3 had a positive likelihood ratio of 2.7 for prediction of an 85% reduction in SDAI at month 6. CONCLUSION: Our data suggest that TTV levels increase upon TNF, CD20 and costimulation blockade and are associated with the clinical response to bDMARDs in RA patients. TRIAL REGISTRATION: ClinicalTrials.gov; https://clinicaltrials.gov; NCT01638715.

Role of joint damage, malalignment and inflammation in articular tenderness in rheumatoid arthritis, psoriatic arthritis and osteoarthritis.

OBJECTIVES: To determine whether clinical tenderness can be considered a sign of inflammatory joint activity in patients with rheumatoid arthritis (RA), osteoarthritis (OA) or psoriatic arthritis (PsA) and to assess other possible factors associated with tenderness. METHODS: Patients diagnosed with RA, PsA and OA underwent clinical and ultrasound examination of wrists and finger joints. Radiographs of the hands were scored for erosions, joint space narrowing (JSN), osteophytes and malalignment. A binary damage score (positive if ≥1 erosion, JSN and/or presence of malalignment) was calculated. Differences in grey scale signs of synovitis and power Doppler (PD) between tender non-swollen (TNS) versus non-tender non-swollen (NTNS) joints were calculated. Disease duration was assessed,<2 years was regarded as early and >5 years as long-standing arthritis. RESULTS: In total, 34 patients (9 early and 14 long-standing) from patients with RA, 31 patients (7 early and 15 long-standing) with PsA and 30 with OA were included. We found equal frequencies of PD signal between TNS and NTNS joints in RA (p=0.18), PsA (p=0.59) or OA (p=0.96). However, PD had a significant association with tenderness in early arthritis both in RA (p=0.02) and in PsA (p=0.02). The radiographic damage score showed significant association with tenderness in RA (p<0.01), PsA (p<0.01) and OA (p=0.04). CONCLUSION: Tenderness might not always be a sign of active inflammation in RA, PsA and OA. While tenderness in early arthritis may be more related to inflammation, established disease is better explained by joint damage and malalignment.

From individualised treatment goals to personalised rehabilitation in osteoarthritis: a longitudinal prospective mapping study using the WHO international classification for functioning, disability and health.

BACKGROUND/OBJECTIVE(S)/INTRODUCTION: In clinical practice, treatment goals are often set up without exploring what patients really want. We, therefore, collected individualised treatment goals of patients with osteoarthritis (OA), categorised and mapped them to the World Health Organisation International Classification for Functioning, Disability and Health (ICF). PATIENTS/MATERIALS AND METHODS: A longitudinal prospective cohort study was conducted (2019-2021). We used descriptive statistics and Chi2/Fisher's Exact Tests, where appropriate, as well as Kruskal-Wallis-Tests for the mean score ranks of the patients' goals. RESULTS: In total, 305 goals reported by 132 participants were analysed (267 women vs. 38 men). The top 3 ICF categories were sensation of pain (ICF:b280), mobility of joint (ICF:b710) and muscle power functions (ICF:b730). Overall, 51% of all individually reported functional goals were achieved after 3 months. Men were more likely to achieve their goals than women (p = 0.009). The majority of the "very important" goals (51%) and "very difficult" goals (57%) was not improved. Goals' mean score ranks significantly differed between baseline and follow-up. CONCLUSION(S): As the human lifespan as well as the number of people affected by OA worldwide increase, there is a growing need to identify and evaluate rehabilitation outcomes that are relevant to people with OA.Key MessagesTreat-to-target agreements between patients and health care providers present a step towards more personalised precision medicine, which will eventually lead to better reported functional and health outcomes.In patients with osteoarthritis, the Goal Attainment Scale instrument can be used to measure health outcomes at different time points and its content may be linked to ICF providing a unified language and conceptual scientific basis.

The Experiences of Functioning and Health of Patients With Primary Sjögren's Syndrome: A Multicenter Qualitative European Study.

Objective: To identify a spectrum of perspectives on functioning and health of patients with primary Sjögren's syndrome (pSS) from the five European countries in order to reveal commonalities and insights in their experiences. Methods: A multicenter focus group study on the patients with pSS about their perspectives of functioning and health was performed. Focus groups were chaired by trained moderators based on an interview guide, audiotaped, and transcribed. After conducting a meaning condensation analysis of each focus group, we subsequently combined the extracted concepts from each country and mapped them to the International Classification of Functioning, Disability and Health (ICF). Results: Fifty-one patients with pSS participated in 12 focus groups. We identified a total of 82 concepts meaningful to people with pSS. Of these, 55 (67%) were mentioned by the patients with pSS in at least four of five countries and 36 (44%) emerged in all the five countries. Most concepts were assigned to the ICF components activities and participation (n = 25, 30%), followed by 22 concepts (27%) that were considered to be not definable or not covered by the ICF; 15 concepts (18%) linked to body structures and functions. Participants reported several limitations in the daily life due to a mismatch between the capabilities of the person, the demands of the environment and the requirements of the activities. Conclusion: Concepts that emerged in all the five non-English speaking countries may be used to guide the development and adaption of the patient-reported outcome measures and to enhance the provision of treatment options based on the aspects meaningful to patients with pSS in clinical routine.

Doubtful swelling on clinical examination reflects synovitis in rheumatoid arthritis.

AIMS: The aim of this study was to evaluate the implication of doubtful joint swelling on clinical examination with respect to objective markers of synovitis by ultrasound (US) in patients with rheumatoid arthritis (RA). METHODS: Two independent observers performed a modified 28 swollen joint assessment (28SJC), in which joints could be graded as either definitely swollen, non-swollen, or doubtfully swollen. Two examiners blinded to clinical information performed US assessment of the hands. We performed descriptive statistics and models to analyse the links between clinical assessment and objective markers of inflammation. RESULTS: A total of 1204 joints were evaluated in 43 RA patients; 93% (40/43) of patients had ⩾1 joint with doubtful swelling (range: 0-4/patient). Inter-reader reliability for the modified 28SJC was good (0.74). Generally, both grey scale (GS) and power Doppler (PD) discriminated across not swollen, doubtful, and swollen joints. GS signals discriminated better than PD between doubtful swelling and no swelling [odds ratio (OR) for GS: 5.2; 95% confidence interval (CI) 1.2-23.3 versus OR for PD 1.7; 95% CI 0.2-13.0], whereas PD discriminated better than GS between swelling and doubtful swelling (OR for PD: 28.7; 95% CI 3.6-228.2 versus GS: 1.7; 95% CI 0.3-8.4). Joint osteophytes did not increase the degree of doubtfulness. CONCLUSION: Clinical doubt in the assessment of joint swelling constitutes an intermediate state between unequivocal swelling and the lack thereof also regarding the objectively quantified level of inflammation. In order to increase sensitivity for joint inflammation, the historical clinical approach of considering doubtful swelling the absence of swelling should be revisited to interpret clinical doubtfulness as an indication of swelling.