Disease interception with interleukin-17 inhibition in high-risk psoriasis patients with subclinical joint inflammation—data from the prospective IVEPSA study

Background A specific subset of psoriasis patients is characterized by subclinical inflammatory changes. These patients frequently present with arthralgia and have a higher risk to develop psoriatic arthritis (PsA). We hypothesized that IL-17A inhibition in this subset of patients can intercept the link between skin and joint disease and resolves pain and inflammatory changes. Methods Psoriasis, but no PsA, patients were included in the open prospective exploratory Interception in very early PsA (IVEPSA) study. Patients had to have nail or scalp involvement or a high psoriasis area severity index (PASI) (> 6) as well as inflammatory or erosive changes in MRI or CT. Patients received treatment with the anti-interleukin (IL)-17A antibody secukinumab over 24 weeks. Clinical assessments of skin and joint disease were done at baseline and after 12 and 24 weeks, MRI and CT at baseline and after 24 weeks. Results Twenty patients were included, 85% of them reporting arthralgia and 40% had tender joints at the examination. Eighty-three percent had at least one inflammatory lesion in the MRI, most of them synovitis/enthesitis. Skin disease (PASI: p < 0.002; BSA: p < 0.003) and arthralgia (VAS pain: p < 0.003) significantly improved after 24 weeks. Total PsAMRIS (p = 0.005) and synovitis subscore (p = 0.008) also significantly improved. Erosions and enthesiophytes did not progress, while bone mass in the distal radius significantly (p = 0.020) increased after 24 weeks. Conclusions These data suggest that very early disease interception in PsA is possible leading to a comprehensive decline in skin symptoms, pain, and subclinical inflammation. IVEPSA therefore provides rationale for future early interventions with the concept to prevent the onset of PsA in high-risk individuals. Trial registration Trial registry name PSARTROS; trial registry number: NCT02483234; June 26, 2015

Effect of disease-modifying anti-rheumatic drugs on bone structure and strength in psoriatic arthritis patients

Objectives To address whether the use of methotrexate (MTX) and biological disease-modifying anti-rheumatic drugs (bDMARDs) impacts bone structure and biomechanical properties in patients with psoriatic arthritis (PsA). Methods This is a cross-sectional study in PsA patients receiving no DMARDs, MTX, or bDMARDs. Volumetric bone mineral densities (vBMDs), microstructural parameters, and biomechanical properties (stiffness/failure load) were determined by high-resolution peripheral quantitative CT and micro-finite element analysis in the respective groups. Bone parameters were compared between PsA patients with no DMARDs and those receiving any DMARDs, MTX, or bDMARDs, respectively. Results One hundred sixty-five PsA patients were analyzed, 79 received no DMARDs, 86 received DMARDs, of them 52 bDMARDs (TNF, IL-17- or IL-12/23 inhibitors) and 34 MTX. Groups were balanced for age, sex, comorbidities, functional index, and bone-active therapy, while disease duration was longest in the bDMARD group (7.8 ± 7.4 years), followed by the MTX group (4.6 ± 7.4) and the no-DMARD group (2.9 ± 5.2). No difference in bone parameters was found between the no-DMARD group and the MTX group. In contrast, the bDMARD group revealed significantly higher total (p = 0.001) and trabecular vBMD (p = 0.005) as well as failure load (p = 0.012) and stiffness (p = 0.012). In regression models, age and bDMARDs influenced total vBMD, while age, sex, and bDMARDs influenced failure load and stiffness. Conclusion Despite longer disease duration, bDMARD-treated PsA patients benefit from higher bone mass and better bone strength than PsA patients receiving MTX or no DMARDs. These data support the concept of better control of PsA-related bone disease by bDMARDs

Machine learning-based improvement of an online rheumatology referral and triage system

IntroductionRheport is an online rheumatology referral system allowing automatic appointment triaging of new rheumatology patient referrals according to the respective probability of an inflammatory rheumatic disease (IRD). Previous research reported that Rheport was well accepted among IRD patients. Its accuracy was, however, limited, currently being based on an expert-based weighted sum score. This study aimed to evaluate whether machine learning (ML) models could improve this limited accuracy.Materials and methodsData from a national rheumatology registry (RHADAR) was used to train and test nine different ML models to correctly classify IRD patients. Diagnostic performance was compared of ML models and the current algorithm was compared using the area under the receiver operating curve (AUROC). Feature importance was investigated using shapley additive explanation (SHAP).ResultsA complete data set of 2265 patients was used to train and test ML models. 30.5% of patients were diagnosed with an IRD, 69.3% were female. The diagnostic accuracy of the current Rheport algorithm (AUROC of 0.534) could be improved with all ML models, (AUROC ranging between 0.630 and 0.737). Targeting a sensitivity of 90%, the logistic regression model could double current specificity (17% vs. 33%). Finger joint pain, inflammatory marker levels, psoriasis, symptom duration and female sex were the five most important features of the best performing logistic regression model for IRD classification.ConclusionIn summary, ML could improve the accuracy of a currently used rheumatology online referral system. Including further laboratory parameters and enabling individual feature importance adaption could increase accuracy and lead to broader usage

Hepatitis-E-Virus-Infektion bei einem Patienten mit rheumatoider Arthritis unter Baricitinib-Therapie

A patient with rheumatoid arthritis (RA) was presented, who developed an infection with the hepatitis E virus (HEV) under treatment with the Janus kinase (JAK) 1 and 2 inhibitor baricitinib. In the 3‑month routine check-up the patient had clearly elevated transaminase levels with an inconspicuous physical examination. The investigations detected antibodies of IgM and IgG classes against HEV and an elevated C‑reactive protein (CRP) level as well as HEV-RNA by real-time PCR, which is indicative of a recent HEV infection. Baricitinib was immediately discontinued. The extensive anamnesis revealed that the patient had eaten beef tartar some days before the consultation, without the occurrence of gastrointestinal symptoms or fever. In the further course the patient completely recovered and the liver function tests and the CRP levels normalized within 3 months. Baricitinib was then restarted. So far only few reports have been published on HEV infections in RA patients who have been treated with JAK inhibitors

Efficacy and drug persistence of baricitinib monotherapy is similar to combination therapy in patients with active RA: a prospective observational study

Background Baricitinib (BARI) is approved for the treatment of rheumatoid arthritis (RA) after failure of conventional synthetic and biologic disease modifying anti-rheumatic drugs (cs/bDMARDs) in combination with methotrexate (MTX) or as monotherapy. However, real-world data are scarce regarding efficacy and drug persistence for BARI monotherapy (BARI-mono) versus its combination with MTX (BARI-combo).Objective To evaluate efficacy and drug persistence of BARImono compared with BARI-combo in routine clinical practiceMethods Patients with RA who were switched to BARI were included in a prospective, monocentric cohort. Demographics, clinical outcomes, adverse events and medication were prospectively recorded every 3 months. Clinical efficacy was measured by DAS-28 ESR while drug persistence was measured as the time on drug. We estimated least-square mean DAS-28 scores over time using linear mixed effects models including time-group interactions. Kaplan-Meier method was used to estimate BARI survival and probability of remission over time.Results 139 patients (98 women; aged 58.4 (12.8) years; mean disease duration of 9.7 years) were included between 2017 and 2021. 46 patients received BARI-combo, 93 patients received BARI-mono. Mean DAS-28 ESR were not significantly but only numerically different between both groups at baseline and multiple timepoints over follow-up. DAS-28 ESR remission was attained at least once upto 48 weeks in 62% and 51% patients in BARI-combo versus BARI-mono group (log-rank p=0.64). Drug persistence was high (69 vs 67% at 48 weeks and 62% vs 56% at 96 weeks) and similar in BARI-combo-treated and BARI-mono-treated patients. b/ts DMARD naïve patients had lower mean DAS-28 scores over the follow-up and attained DAS-28 ESR remission earlier than patients with inadequate response to b/ts DMARDs (p=0.11). BARI was discontinued in 11/139 patients (7.9%) due to adverse effects.Conclusion In routine practice, BARI is effective as monotherapy in case of MTX intolerance with overall high drug persistence rates. No new safety signals were observed

Tolerability of low to moderate biomechanical stress during leisure sport activity in patients with psoriasis and psoriatic arthritis

Objectives To assess the impact of low to moderate biomechanical stress on entheses in patients with psoriasis and psoriatic arthritis (PsA).Methods We conducted a prospective interventional study on a cohort of psoriasis and PsA patients who underwent a 60 min badminton training session. Pain assessment by Visual Analogue Scale (VAS), physical examination of 29 entheses (SPARCC, LEI, MASES) and bilateral ultrasound at the lateral humeral epicondyle, inferior patellar pole and Achilles tendon were performed before and after training. Ultrasound changes were assessed using the OMERACT scoring system. A follow-up assessment of pain and adverse events was performed at 1 week.Results Sixteen patients were included (n=7 PsA; n=9 psoriasis) and 196 entheseal ultrasound scans were acquired. At baseline, median VAS pain (IQR) was 0.5 cm (0–2.3) and the total number of tender entheses was 12/464. Mean (min; max) Disease Activity Index for Psoriatic Arthritis was 6.1 (0.8; 19) and 5/7 PsA patients had an Minimal Disease Activity status. After training, no significant change in VAS pain (0.0 cm (0.0–2.0)) nor in tender entheses (13/464) emerged. Four patients (n=2 PsA, n=2 psoriasis) developed a grade-1 power Doppler-signal at six entheses, which, however, remained non-tender. At 1 week, median VAS pain remained stable (0.0 cm (0.0–3.0); p&gt;0.05) and only one participant with active PsA at baseline reported increased arthralgias in three joints.Conclusions Low to moderate physical strain, as in the context of leisure sport activity, seems well tolerated in psoriatic patients without increases in tenderness, pain and ultrasound-proven inflammation. Evidence-based recommendations for physical activity in PsA are direly needed and larger controlled studies should be conducted to define safe exercise thresholds

Performance of a Handheld Ultrasound Device to Assess Articular and Periarticular Pathologies in Patients with Inflammatory Arthritis

The purpose of this study was to assess the accuracy and performance of a new handheld ultrasound (HHUS) machine in comparison to a conventional cart-based sonographic machine in patients with inflammatory arthritis (IA). IA patients with at least one tender and swollen joint count were enrolled. US was performed on the clinically affected joints using a cart-based sonographic device (Samsung HS40) and a HHUS device (Butterfly iQ). One blinded reader scored all images for the presence of erosions, bony enlargement, synovial hypertrophy, joint effusion, bursitis, tenosynovitis, and enthesitis. Synovitis was graded (B mode and power Doppler (PD)) by the 4-level EULAR-OMERACT scale. To avoid bias by the blinded reader, we included 67 joints of two healthy volunteers in the evaluation. We calculated the overall concordance and the concordance by type of joint and pathological finding. We also measured the time required for the US examination per joint with both devices. Thirty-two patients (20 with RA, 10 with PsA, and one each with gout and SLE-associated arthritis) were included, and 186 joints were examined. The overall raw concordance in B mode was 97% (κappa 0.90, 95% CI (0.89, 0.94)). In B mode, no significant differences were found in relation to type of joint or pathological finding examined. The PD mode of the HHUS device did not detect any PD signal, whereas the cart-based device detected a PD signal in 61 joints (33%). The portable device did not offer any time savings compared to the cart-based device (47.0 versus 46.3 s). The HHUS device was accurate in the assessment of structural damage and inflammation in patients with IA, but only in the B mode. Significant improvements are still needed for HHUS to reliably demonstrate blood flow detection in PD mode

Changes in T2 Relaxation Time Mapping of Intervertebral Discs Adjacent to Vertebrae after Kyphoplasty Correlate with the Physical Clinical Outcome of Patients

(1) Background: To assess whether clinical outcomes correlate with tissue changes in the intervertebral discs (IVDs) after kyphoplasty as treatment for vertebral fractures, quantitative MRI was applied. (2) Methods: Quantitative T2 mapping acquired in a 3 T MRI scanner of the thoracolumbar spine was performed in 20 patients two years after kyphoplasty. The IVDs adjacent and nonadjacent to the treated vertebrae were divided into six regions of interest (ROI), which were further categorised into inner (ROI 2&ndash;5) and outer (ROI 1 and 6) parts of the IVDs, and the T2 values were analysed. T2 values of adjacent discs were correlated with the items of questionnaires evaluating the clinical outcome (i.e., 36-Item Short Form Survey). (3) Results: Lower T2 values in adjacent IVDs correlated with poorer physical outcome two years after kyphoplasty. The inner part of the IVDs adjacent to treated vertebrae showed statistically significant lower T2 values in segments L2/L3 and L3/L4 compared to nonadjacent ones. Patients with lower T2 values showed more pain and physical limitations in everyday life. (4) Conclusions: Quantitative T2 mapping can detect IVD degeneration in patients after kyphoplasty and correlates with the physical outcome. This technique could help to gain better insights into alterations in tissue composition following kyphoplasty and the consequences for the patients&rsquo; quality of life