Real-World Efficacy and Safety of Apremilast in Belgian Patients with Psoriatic Arthritis: Results from the Prospective Observational APOLO Study.

INTRODUCTION: Apremilast is approved for the treatment of psoriasis and psoriatic arthritis (PsA). Real-world evidence on the efficacy and safety of apremilast in clinical practice is limited. We assessed the use of apremilast in patients with PsA in Belgium clinical practice. METHODS: The multicentre, observational, prospective APOLO study enrolled patients with active PsA initiating apremilast in Belgium between April 2017 and December 2018. Primary outcome was PsA Response Criteria (PsARC) after 6 months of apremilast treatment. Secondary outcomes included PsA Impact of Disease 12 (PsAID12) and Health Assessment Questionnaire Disability Index (HAQ-DI). Disease-specific outcomes and patient-reported outcomes (PROs) were analysed for patients who received apremilast within 30 days prior to their study inclusion and completed at least 150 days of treatment (reference set [REF]). RESULTS: Of 107 patients enrolled in the study, 106 received at least one dose of apremilast and 69 were included in the REF. PsARC response was achieved by 43.5% of patients (30/69) in the REF at month 6; mean global and composite scores including 68-joint count for pain/tenderness (68-TJC) and 66-joint count for swelling (66-SJC) improved, and 27% and 42% of patients with 68-TJC and 66-SJC > 0 at baseline had complete joint count resolution, respectively. Mean global and composite PsAID12 and HAQ-DI scores decreased at 6 months, indicating improved quality of life. Apremilast was well tolerated and the reported adverse events were in line with the known safety profile. CONCLUSION: Results from the APOLO study indicate that treatment with apremilast in Belgian clinical practice improves the signs and symptoms of PsA as well as patient quality of life. CLINICALTRIALS. GOV IDENTIFIER: NCT03096990.

ImmunoStart: preparing patients for immunosuppression.

OBJECTIVES: Patients with immune-mediated inflammatory disease (IMID) present an increased risk of infection. Here, we present the concept of a preventive consultation called ImmunoStart and the first results of its implementation in the care pathway of patients with IMID. METHODS: Relevant information about vaccination history, tuberculosis exposure and other infectious risks were collected through blood sampling, complete anamnesis, chest X-ray and Mantoux test. During the ImmunoStart consultation, vaccination schedules, specific treatments and risk considerations were discussed. RESULTS: Between October 2016 and February 2020, 437 patients were seen at an ImmunoStart consultation, mainly referred by rheumatologists (56%), dermatologists (25%) and gastroenterologists (18%). A total of 421 (96%) patients needed at least one vaccine (a mean of 3.3 vaccines per patient). Live attenuated vaccine was indicated for 45 patients (10%), requiring them to reduce or interrupt their immunosuppressive drug(s). Ninety-two patients (21%) were treated for latent tuberculosis infection. CONCLUSION: This preventive consultation provides a centralized and systematic setting for the direct management of patients with IMID in need of vaccination, treatment of latent disease and specific advice regarding their immunomodulating treatments.

A Cross-Sectional and Longitudinal Study to Define Alarmins and A-SAA Variants as Companion Markers in Early Rheumatoid Arthritis.

Nowadays, in the study of rheumatoid arthritis (RA), more and more interest is directed towards an earlier effective therapeutic intervention and the determination of companion markers for predicting response to therapy with the goal to prevent progressive joint damage, deformities, and functional disability. With the present work, we aimed at quantifying in a cohort of early RA (ERA) patients naïve to DMARD therapy, proteins whose increase was previously found associated with RA: serum amyloid A (A-SAA) and alarmins. Five A-SAA variants (SAA1α, SAA1ß, SAA1γ, SAA2α, and SAA2ß) but also S100A8 and S100A9 proteins were simultaneously quantified in plasma applying a method based on single targeted bottom-up proteomics LC-MS/MS. First, we compared their expression between ERA (n = 100) and healthy subjects (n = 100), then we focused on their trend by monitoring ERA patients naïve to DMARD treatment, 1 year after starting therapy. Only SAA1α and SAA2α levels were increased in ERA patients, and SAA2α appears to mostly mediate the pathological role of A-SAA. Levels of these variants, together with SAA1ß, only decreased under biologic DMARD treatment but not under methotrexate monotherapy. This study highlights the importance to better understand the modulation of expression of these variants in ERA in order to subsequently better characterize their biological function. On the other hand, alarmin expression increased in ERA compared to controls but remained elevated after 12 months of methotrexate or biologic treatment. The work overcomes the concept of considering these proteins as biomarkers for diagnosis, demonstrating that SAA1α, SAA1ß, and SAA2α variants but also S100A8 and S100A9 do not respond to all early treatment in ERA and should be rather considered as companion markers useful to improve the follow-up of treatment response and remission state. Moreover, it suggests that earlier use of biologics in addition to methotrexate may be worth considering.

Glycosylation deficiency of lipopolysaccharide-binding protein and corticosteroid-binding globulin associated with activity and response to treatment for rheumatoid arthritis.

BACKGROUND: Serum protein glycosylation is an area of investigation in inflammatory arthritic disorders such as rheumatoid arthritis (RA). Indeed, some studies highlighted abnormalities of protein glycosylation in RA. Considering the numerous types of enzymes, monosaccharides and glycosidic linkages, glycosylation is one of the most complex post translational modifications. By this work, we started with a preliminary screening of glycoproteins in serum from RA patients and controls. METHODS: In order to isolate glycoproteins from serum, lectin wheat germ agglutinin was used and quantitative differences between patients and controls were investigated by LC-MS/MS. Consequently, we focused our attention on two glycoproteins found in this explorative phase: corticosteroid-binding globulin (CBG) and lipopolysaccharide-binding protein (LBP). The subsequent validation with immunoassays was widened to a larger number of early RA (ERA) patients (n = 90) and well-matched healthy controls (n = 90). RESULTS: We observed a significant reduction of CBG and LBP glycosylation in ERA patients compared with healthy controls. Further, after 12 months of treatment, glycosylated CBG and LBP levels increased both to values comparable to those of controls. In addition, these changes were correlated with clinical parameters. CONCLUSIONS: This study enables to observe that glycosylation changes of CBG and LBP are related to RA disease activity and its response to treatment.