Josef Sebastian Smolen

Objective: To test whether ultrasonography of patients with rheumatoid arthritis (RA) in the American College of Rheumatology/the European Alliance of Associations for Rheumatology (ACR/EULAR) remission is useful for prediction of relapse after discontinuation of a biological disease-modifying antirheumatic drug (bDMARD). Methods: Prospective trial including patients with RA in persistent ACR/EULAR remission treated with conventional synthetic DMARDs plus bDMARDs. After stopping the bDMARD, nine study visits including clinical examination and ultrasound of 14 joints (blinded to clinical data) were conducted within 52 weeks. The primary hypothesis was that a Power Doppler (PD) score≥1 predicted relapse occurring within week 16 after bDMARD cessation. Relapse was defined as a change from remission to moderate/high disease activity according to the Simplified Disease Activity Score. Results: Inclusion of 110 patients was originally planned; however, the study was terminated after reaching 38 (34.5%) patients due to insufficient recruitment. Relapses till week 16 were numerically more common in patients with PD score≥1 at baseline than in those with PD=0 (9/30 (30.0%) vs 0/7 (0%), p=0.160). Similar observations were made for weeks 24 and 52. PD scores were higher at the time of relapse than at preceding visits (mean PD score difference: 3.2 (±4.5) points, p=0.034). There were trends towards a higher baseline PD score in patients who had a relapse until week 16 as compared with those who remained in remission (5.2±5.8 vs 2.3±3.0, p=0.079). Conclusion: The primary endpoint was not reached. The presented data should be interpreted as hypothesis-generating, serving to stimulate future research on the value of ultrasound in assessing remission and predicting relapse in RA. Trial registration number: NCT01602302 .

Objective: The previously developed FLARE questionnaire assesses the multidimensional aspects of a flare of psoriatic arthritis (PsA). We aimed to further validate this questionnaire. Methods: Reanalysis of data from the ReFLAP study (ClinicalTrials.gov: NCT03119805 ), a longitudinal observational study carried out in 14 countries. Demographic, clinical, and patient-reported data were collected at baseline and 1 follow-up visit. The FLARE questionnaire (range 0-10) was completed at both timepoints (mean interval 4.5 months). Using a patient anchor question for perceived flare (yes/no), the optimal cutoff for defining a flare was obtained using receiver-operating characteristic curve analysis. Based on this cutoff, patients were compared for flare (yes/no) using clinical and patient-reported data, including composite measures of disease activity. The magnitude of score differences in patients experiencing a new flare at second visit were compared with independent samples t -scores. Results: Of 147 patients, 61 (41%) reported a flare at baseline; the optimal score cutoff from the FLARE questionnaire was 4 (sensitivity 0.86, specificity 0.76) and, using this cutoff, patients in flare had significantly worse clinical and patient-reported outcomes. Of those patients reporting a flare, the most frequently affirmed items from the questionnaire referred to pain, mobility, frustration, and fatigue. Those with a new flare at the second visit had patient-reported and clinical change scores significantly worse than those not reporting a flare. Conclusion: This study has provided further data on the FLARE questionnaire performance and validity. The questionnaire is ready for use in clinical trials and longitudinal observational studies.

Objectives: To assess the impact of rheumatoid factor (RF) levels and previous inadequate responses/intolerance to tumour necrosis factor inhibitors (TNFi-IR) on the efficacy of certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA) through a post hoc analysis of the RA Evaluation in Subjects Receiving TNF Inhibitor CZP (REALISTIC) trial. Methods: In the phase IIIb REALISTIC trial, patients with RA were randomised to CZP (400 mg at weeks 0, 2 and 4, then 200 mg every 2 weeks) or placebo (PBO) for 12 weeks, followed by open-label CZP (minimum 16 weeks). Outcomes reported to week 36 include Disease Activity Score 28 C-reactive protein (DAS28-CRP) and Clinical Disease Activity Index (CDAI) scores, rates of DAS28-CRP <2.6 and CDAI remission (CDAI ≤2.8) and components of each. Data were stratified by baseline RF level (≤3rd quarter (≤Q3; <180 kU/L) vs 4th quarter (Q4; ‘high RF’; ≥180 kU/L)) and prior TNFi use (TNFinaïve vs TNFi-IR). Results: A total of 930 patients were included: 751 CZP-randomised and 179 PBO-randomised. At week 12, CZP-randomised patients experienced marked and similar improvements in disease activity, irrespective of RF level and prior TNFi use, while PBO-randomised patients did not. Responses generally improved through week 36 in CZP-treated patients (including PBO-randomised switchers), with similar efficacy across subgroups. Conclusions: Patients with high and low RF levels experienced similar clinical responses to CZP treatment, irrespective of previous inadequate responses or intolerance to TNFis. These findings expand previous observations, supporting CZP as an effective treatment for patients with RA who have high RF levels and prior inadequate responses to TNFis. Trial registration number: NCT00717236 .