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Introduction: Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are frequently overlapping conditions. Unlike in GCA, vascular inflammation is absent in PMR. Therefore, serum biomarkers reflecting vascular remodelling could be used to identify GCA in cases of apparently isolated PMR.

Materials and methods: 45 patients with isolated PMR and 29 patients with PMR/GCA overlap were included. Blood samples were collected before starting glucocorticoids for all patients. Serum biomarkers reflecting systemic inflammation (interleukin-6 (IL-6), CXCL9), vascular remodelling (MMP-2, MMP-3, MMP-9) and endothelial function (sCD141, sCD146, ICAM-1, VCAM-1, vWFA2) were measured by Luminex assays.

Results: Patients with GCA had higher serum levels of sCD141 (p=0.002) and CXCL9 (p=0.002) than isolated PMR. By contrast, serum levels of MMP-3 (p=0.01) and IL-6 (p=0.004) were lower in GCA than isolated PMR. The area under the curve (AUC) was calculated for sCD141, CXCL9, IL-6 and MMP-3. Separately, none of them were >0.7, but combinations revealed higher diagnostic accuracy. The CXCL9/IL-6 ratio was significantly increased in patients with GCA (p=0.0001; cut-off >32.8, AUC 0.76), while the MMP-3/sCD141 ratio was significantly lower in patients with GCA (p<0.0001; cut-off <5.3, AUC 0.79). In patients with subclinical GCA, which is the most difficult to diagnose, sCD141 and MMP-3/sCD141 ratio demonstrated high diagnostic accuracy with AUC of 0.81 and 0.77, respectively.

Conclusion: Combined serum biomarkers such as CXCL9/IL-6 and MMP-3/sCD141 could help identify GCA in patients with isolated PMR. It could allow to select patients with PMR in whom complementary examinations are needed.

Objectives: To investigate if patients with early rheumatoid arthritis responding insufficiently to initial methotrexate (MTX) and bridging glucocorticoids (GCs) could benefit from early but temporary etanercept introduction as a second remission-induction attempt.

Methods: CareRA2020 (NCT03649061) was a 2-year, open-label, multicentre, pragmatic randomised controlled trial. Treatment-naïve patients started MTX and GC bridging (COBRA-Slim: CS). Within a time window from week (W) 8 until W32, early insufficient responders (28-joint Disease Activity Score - C-reactive Protein (DAS28-CRP) >3.2 between W8 and W32 or ≥2.6 at W32) were randomised to a Standard-CS strategy (adding leflunomide first) or Bio-induction-CS strategy (adding etanercept for 24 weeks). Additional treatment adaptations followed the treat-to-target principle. Longitudinal disease activity (DAS28-CRP) over 104 weeks (primary outcome), achievement of DAS28-CRP <2.6 28 weeks after randomisation, and biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) use at W104 were compared between randomisation groups.

Results: Following CS treatment, 142 patients were early responders; 55 early insufficient responders received Standard-CS and 55 Bio-induction-CS. Superiority of Bio-induction-CS over Standard-CS could not be demonstrated (ß=-0.204, (95% CI -0.486 to 0.078), p=0.157) for the primary outcome. More patients on Bio-induction-CS achieved DAS28-CRP <2.6 at 28 weeks after randomisation (59% (95% CI 44% to 72%) vs 44% (95% CI 31% to 59%) in Standard-CS) and they were treated less frequently with b/tsDMARDs at W104 (19/55, 35%) compared with Standard-CS (29/55, 53%).

Conclusion: Half of the patients responded well to initial COBRA-Slim induction therapy. In early insufficient responders, adding etanercept for 6 months did not improve disease control over 104 weeks versus adding leflunomide first. However, temporary introduction of etanercept resulted in improved disease control early after randomisation and less patients on b/tsDMARDs at W104.

Trial registration number: NCT03649061.

Ctr pilot approval belgium: S59474, EudraCT number: 2017-004054-41.

Objectives: To assess the potential impact of targeted therapies for psoriatic arthritis (PsA) on symptomatic treatments (non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, opioid analgesics), methotrexate and mood disorder treatments and on hospitalisation and sick leave.

Methods: Using the French health insurance database, this nationwide cohort study included adults with PsA who were new users (not in the year before the index date) of targeted therapies for ≥9 months during 2015-2021. Main endpoints were difference in proportion of users of associated treatments, hospitalisations and sick leaves between 3 and 9 months after and 6 months before targeted therapy initiation. Logistic regression models adjusted for sex, age, psoriasis, inflammatory bowel disease and Charlson Comorbidity Index compared the impact of biologics initiation (tumour necrosis factor inhibitor (TNFi)/interleukin 17 inhibitor (IL17i)/IL12/23i) on associated treatment discontinuation.

Results: Among 9793 patients initiating targeted therapy for PsA (mean age: 51±13 years, 47% men), 62% initiated TNFi, 14% IL17i, 10% IL12/23i, 1% Janus kinase inhibitor, 12% phosphodiesterase-4 inhibitor. After treatment initiation, the proportion of treatment users was significantly reduced for NSAIDs (-15%), opioid analgesics (-9%), prednisone (-9%), methotrexate (-15%) and mood disorder treatments (-2%), along with decreased hospitalisations (-12%) and sick leaves (-4%). TNFi had a greater sparing effect on NSAIDs and prednisone use than IL17i (OR_a=1.04, 95% CI=1.01 to 1.07; 1.04, 1.02 to 1.06) and IL12/23i (1.07, 1.04 to 1.10; 1.06, 1.04 to 1.09). Odds of methotrexate discontinuation was reduced with TNFi versus IL17i (0.96, 0.94 to 0.98) and IL12/23i (0.94, 0.92 to 0.97).

Conclusions: Targeted therapy initiation for PsA reduced the use of associated treatment and healthcare, with TNFi having a slightly greater effect than IL17i and IL12/23i, except for methotrexate discontinuation.

Objective: To evaluate the efficacy and safety of upadacitinib over 5 years among patients with rheumatoid arthritis (RA) in a long-term extension (LTE) of the SELECT-BEYOND phase 3 trial.

Methods: Patients refractory to ≥1 biological disease-modifying antirheumatic drug (DMARD) received upadacitinib 15 mg or 30 mg once daily or placebo, in combination with background conventional synthetic DMARD(s). At week 12, patients randomised to placebo were switched to upadacitinib 15 mg or 30 mg. All patients who completed the week 24 visit could enter the LTE for up to 5 years. Efficacy was analysed as observed and by non-responder imputation through week 260. Treatment-emergent adverse events per 100 patient-years were summarised over 5 years.

Results: Of the 498 patients randomised, 418 (84%) completed week 24 and entered the LTE. Of those who remained in the trial (n=80, upadacitinib 15 mg; n=81, upadacitinib 30 mg), 36%/36% and 81%/77% randomised to upadacitinib 15/30 mg were in Clinical Disease Activity Index (CDAI) remission or low disease activity at week 260, respectively (as observed). Approximately 47% of all patients who began in high disease activity demonstrated a CDAI improvement >12 at week 260 with upadacitinib 15/30 mg. Functional and pain-related outcomes also showed comparable improvements with both doses. Numerically higher rates of anaemia, herpes zoster and creatine phosphokinase elevation were observed with upadacitinib 30 mg vs 15 mg. No new safety issues were identified.

Conclusions: Upadacitinib 15/30 mg continued to be effective in treating clinical and functional outcomes in patients with RA. The safety profile observed over 5 years was consistent with earlier study-specific and integrated assessments of upadacitinib treatment.

Objective: To evaluate the sensitivity to change in structural imaging outcomes over 10 years of follow-up in patients with axial spondyloarthritis (axSpA).

Methods: Patients with axSpA from the Devenir des Spondyloarthropathies Indifferénciées Récentes cohort were included. Radiographs and MRIs of the sacroiliac joints (SIJ) and spine were obtained at baseline and at 1, 2, 5 and 10 years. The yearly rate of change of each structural outcome was analysed using generalised estimating equation models, including all patients with ≥1 score from ≥1 reader from ≥1 reading wave, using the time (years) as an explanatory variable and adjusting for reader and wave. All outcomes were standardised, and the relative standardised rate of change was calculated (ie, the standardised rate of an outcome divided by the rate of a reference outcome).

Results: A total of 659 patients (46% males and mean age 33.6 years) were included. The most sensitive outcome to change in the SIJ (both MRI and radiographs) was the presence of ≥3 fatty lesions at a specific timepoint, with a relative standardised rate of change per year of 5.28 using the modified New York criteria as reference.Similarly, the most sensitive to change (in both MRI and radiographs) outcome in the spine was the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS; relative standardised yearly change 1.76) using ≥1 syndesmophyte as reference.

Conclusion: MRI structural outcomes in the SIJ (ie, fatty lesions) are more sensitive to change than radiographic outcomes. Conversely, the mSASSS remains the most sensitive method, even when compared with MRI of the spine.

Objective: To evaluate the long-term sustainability of response to the Janus kinase inhibitor upadacitinib among patients with rheumatoid arthritis and an inadequate response or intolerance to biological disease-modifying antirheumatic drugs (bDMARD-IR) in the SELECT-BEYOND phase 3 trial.

Methods: Patients on background conventional synthetic DMARDs (csDMARDs) were treated once daily with upadacitinib 15 mg or placebo. Patients who completed the week 24 visit could enter a long-term extension of up to 5 years. The sustainability of response was assessed based on achievement of Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and Disease Activity Score 28-joint count using C-reactive protein (DAS28 (CRP)) targets and evaluated up to week 260 in all patients receiving the approved upadacitinib 15 mg dose, including those randomised to upadacitinib 15 mg and those who switched from placebo to upadacitinib 15 mg at week 12.

Results: In this bDMARD-IR population, 45% (n=104/229) and 79% (n=172/219) of patients treated with upadacitinib 15 mg plus background csDMARD(s) achieved CDAI remission or CDAI low disease activity (LDA) at any point during the 5-year study, respectively. Of those who achieved CDAI remission/LDA, 25%/43% maintained their initial response through 240 weeks of follow-up after first achieving response. Most patients who lost remission or LDA were able to recapture that response by the cut-off date. Similar overall results were observed for SDAI and DAS28 (CRP). No strong predictors of response were identified.

Conclusions: Over three-quarters of bDMARD-IR patients achieved CDAI LDA with upadacitinib, and almost half of those maintained LDA through 240 weeks of follow-up. Remission was achieved by nearly half of all patients and maintained in approximately a quarter of those achieving remission.

Trial registration number: NCT02706847.

Objectives: While important progress was made regarding the treatment of systemic sclerosis (SSc), there is still no evidence-based disease-modifying treatment available for SSc-related gastrointestinal (GI) manifestations. We aimed to identify an association between immunosuppressive therapy and the the severity of GI symptoms, measured by the University of California at Los Angeles/Scleroderma Clinical Trial Consortium Gastro-Intestinal Tract instrument 2.0 (GIT).

Methods: We selected patients with SSc who had at least two visits (further referred to as 'baseline' and 'follow-up') with completed GITs, within an interval of 12±3 months. The study outcome was the GIT score at follow-up. We used multivariable linear regression with the following covariates: immunosuppressive therapy during observation, immunosuppressive therapy before baseline, baseline GIT and several baseline parameters selected by clinical judgement as potentially influencing GI symptoms.

Results: We included 209 SSc patients (82.3% female, median age 59.0 years, median disease duration 6.0 years, 40 (19.1%) diffuse cutaneous SSc, median baseline GIT 0.19). Of these, 71 were exposed to immunosuppressive therapy during the observation period, and, compared with unexposed patients, had overall more severe SSc and a higher prevalence of treatment with proton pump inhibitors. In multivariable linear regression, immunosuppressive therapy during the period of observation and lower baseline GIT scores were significantly associated with lower (better) GIT scores at follow-up.

Conclusion: Immunosuppressive treatment was associated with lower GIT scores in our cohort, which suggests the potential effects of immunosuppressants on GI manifestations in patients with SSc, requiring confirmation in prospective randomised clinical trials.

Objectives: To compare the treatment effectiveness of secukinumab in radiographic (r) versus non-radiographic (nr) axial spondyloarthritis (axSpA) patients treated in routine care across Europe.

Methods: Prospectively collected data on secukinumab-treated axSpA patients with known radiographic status were pooled from nine countries.Remission rates based on patient-reported outcomes (PROs; Numeric Rating Scale (0-10), for example, pain ≤2/Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≤2 and Ankylosing Spondylitis Disease Activity Score (ASDAS) inactive disease (ID) <1.3 after 6/12/24 months of secukinumab treatment were calculated.Remission and drug retention rates in r-axSpA versus nr-axSpA patients were compared by logistic and Cox regression models (unadjusted/adjusted for age+sex/adjusted for multiple confounders).

Results: Overall, 1161 secukinumab-treated patients were included (r-axSpA/nr-axSpA: 922/239). At baseline, r-axSpA patients had longer disease duration and higher C reactive protein, were more often male and HLA-B27 positive and had received fewer prior biological or targeted synthetic disease-modifying antirheumatic drugs compared with nr-axSpA patients, whereas PROs were largely similar.During follow-up, crude PRO remission rates were significantly higher in r-axSpA compared with nr-axSpA patients (6 months: pain≤2: 40%/28%, OR=1.7; BASDAI≤2: 37%/25%, OR=1.8), as were drug retention rates (24 months: 66%/58%, HR 0.73 (ref: r-axSpA)). Proportions of patients achieving ASDAS ID were low for both groups, particularly nr-axSpA (6 months: 11%/8%).However, when adjusting for age+sex, these differences diminished, and after adjusting for multiple confounders, no significant between-group differences remained for either remission or drug retention rates.

Conclusion: Crude remission/drug retention rates in European secukinumab-treated patients were higher in r-axSpA compared with nr-axSpA patients. In adjusted analyses, secukinumab effectiveness was similar in both groups, suggesting that observed differences were related to factors other than radiographic status.

Background: The potential benefit of methotrexate (MTX) in combination with biologic (b) and targeted synthetic (ts) disease modifying anti-rheumatic drugs (DMARDs) in psoriatic arthritis (PsA) is still a matter of debate.

Objectives: To compare clinical and patient reported characteristics as well as drug retention rates in PsA patients receiving b/tsDMARD monotherapy or in combination with MTX.

Methods: RABBIT-SpA is a prospective longitudinal cohort study including axSpA and PsA patients. In this analysis, PsA patients were stratified into two groups: starting b/tsDMARD as monotherapy or in combination with MTX. Treatment retention was compared by drug survival analysis.

Results: 69% of the patients (n=900) started b/tsDMARD as monotherapy while 31% were treated in combination with MTX (n=405). At baseline, clinical domains like skin, nail and joint affection, dactylitis, enthesitis and axial involvement were similar between the groups. Only the patients' satisfaction concerning tolerability of the previous treatment was significantly better in the combination group at treatment start. Drug retention rates did not differ between the groups (p=0.4). At 6/12 months, 66%/48% of patients in monotherapy and 67%/48% in the combination group were still on their original treatment.

Conclusions: We did not identify any clinical parameters with notable influence on the choice of b/tsDMARD mono or MTX-combination therapy in PsA. Drug retention rates are similar between mono and combination therapy. It seems that the decision to continue MTX at initiation of b/tsDMARDs is mostly based on the subjective tolerability of MTX treatment.

Objectives: Chronic inflammation promotes cardiovascular risk in rheumatoid arthritis (RA). Biological disease-modifying antirheumatic drugs (bDMARDs) improve disease activity and cardiovascular disease outcomes. We explored whether bDMARDs influence the impact of disease activity and inflammatory markers on long-term cardiovascular risk in RA.

Methods: We studied 4370 participants without cardiovascular disease in a 10-country observational cohort of patients with RA. Endpoints were (1) major adverse cardiovascular events (MACE) encompassing myocardial infarction, stroke and cardiovascular death; and (2) any ischaemic cardiovascular events (iCVE) including MACE plus revascularisation, angina, transient ischaemic attack and peripheral arterial disease.

Results: Over 26 534 patient-years, 239 MACE and 362 iCVE occurred. The interaction between 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and bDMARD use was significant for MACE (p=0.017), suggesting the effect of DAS28-CRP on MACE risk differed among bDMARD users (n=515) and non-users (n=3855). DAS28-CRP (per unit increase) is associated with MACE risk in bDMARD non-users (HR 1.21 (95% CI 1.07 to 1.37)) but not users (HR 0.69 (95% CI 0.40 to 1.20)). The interaction between CRP (per log unit increase) and bDMARD use was also significant for MACE (p=0.011). CRP associated with MACE risk in bDMARD non-users (HR 1.16 (95% CI 1.04 to 1.30)), but not users (HR 0.65 (95% CI 0.36 to 1.17)). No interaction was observed between bDMARD use and DAS28-CRP (p=0.167) or CRP (p=0.237) for iCVE risk.

Conclusions: RA activity and inflammatory markers associated with risk of MACE in bDMARD non-users but not users suggesting the possibility of biological-specific benefits locally on arterial wall independently of effects on systemic inflammation.