Objectives To investigate whether biomarkers are modulated by prednisolone treatment in patients with hand OA and whether they can predict response to prednisolone. Methods Biomarkers reflecting... Show moreObjectives To investigate whether biomarkers are modulated by prednisolone treatment in patients with hand OA and whether they can predict response to prednisolone. Methods Biomarkers reflecting tissue turnover and inflammation [aggrecanase-derived neoepitope of arggecan (ARGS), MMP-derived neoepitope of type I collagen (C1M), MMP-derived neoepitope of type III collagen (C3M), marker of true type V collagen formation (PROC5), MMP-derived neoepitope of CRP (CRPM), citrullinated vimentin fragment (VICM), high-sensitivity (hsCRP)] were measured in sera from 78 patients with painful inflammatory hand OA, who were randomized between prednisolone or placebo treatment. Association of baseline biomarker levels with disease characteristics [visual analogue scale (VAS) pain, synovial thickening ultrasonography sum score and erosive OA] and OMERACT-Osteoarthritis Research Society International (OARSI) response after 6 weeks were analysed with linear or logistic regression and adjusted for age, BMI and sex. Change in biomarker levels after 6 weeks was assessed with linear regression adjusted for baseline biomarker levels, age, BMI and sex. Results For all patients (mean age 64 years, 79% female), there were no associations between biomarker levels and VAS finger pain or synovial thickening score at baseline. Patients with erosive hand OA had higher levels of C1M and hsCRP [adjusted geometric mean ratio 1.24 (95% CI 1.03, 1.49) and 1.91 (1.19, 3.06), respectively]. Biomarker levels did not decrease over time. There was no association between baseline biomarkers levels and OARSI response, except for CRPM [geometric mean ratio of 0.88 (0.77, 1.00)]. Conclusion Erosive disease was associated with higher levels of C1M and hsCRP. Biomarker levels were not influenced by treatment with prednisolone. Current biomarkers were not associated with response to prednisolone in hand OA. Show less
Kroon, F.P.B.; Heijde, D. van der; Maxwell, L.J.; Beaton, D.E.; Abishek, A.; Berenbaum, F.; ... ; Kloppenburg, M. 2021
Objective: Physical function is one of the Outcome Measures in Rheumatology (OMERACT) core outcome domains for hand osteoarthritis studies. Our aim was to select appropriate instrument(s) to... Show moreObjective: Physical function is one of the Outcome Measures in Rheumatology (OMERACT) core outcome domains for hand osteoarthritis studies. Our aim was to select appropriate instrument(s) to measure this domain, as part of the development of a core outcome measurement set.Methods: Following the OMERACT Filter 2.1 instrument selection process, the (function subscale of) the Australian/Canadian Hand Osteoarthritis Index (AUSCAN), Functional Index for Hand Osteoarthritis (FIHOA) and Michigan Hand Outcomes Questionnaire (MHQ) were assessed for domain match, feasibility, truth and discrimination. Data gathered from available literature, working group and patient surveys, and additional analyses in two hand osteoarthritis cohorts were used to inform a consensus process.Results were summarized in Summary of Measurements Properties tables and reviewed by the OMERACT technical advisory group. Results: MHQ passed the assessment of domain match and feasibility by the working group and patient research partners. For AUSCAN important limitations in feasibility were noted, but domain match was good. FIHOA did not pass the assessment and was not taken through the follow-up assessment. Based on published literature, reliability and construct/longitudinal validity of both MHQ and AUSCAN fulfilled OMERACT standards. While clinical trial discrimination and thresholds of meaning were good for AUSCAN, results for MHQ were ambiguous.Conclusion: MHQ was provisionally endorsed as OMERACT core outcome measure for the core domain physical function. While AUSCAN may have better metric properties than MHQ, it received provisional endorsement as a second measure of function due to important feasibility issues. A research agenda to merit full endorsement was set. (c) 2021 The Author(s). Published by Elsevier Inc. Show less
Stadt, L.A. van de; Kroon, F.P.B.; Kloppenburg, M. 2020
Background Hand osteoarthritis is a prevalent joint condition that has a high burden of disease and an unmet medical need for effective therapeutic options. Since local inflammation is recognised... Show moreBackground Hand osteoarthritis is a prevalent joint condition that has a high burden of disease and an unmet medical need for effective therapeutic options. Since local inflammation is recognised as contributing to osteoarthritic complaints, the Hand Osteoarthritis Prednisolone Efficacy (HOPE) study aimed to investigate the efficacy and safety of short-term prednisolone in patients with painful hand osteoarthritis and synovial inflammation.Methods The HOPE study is a double-blind, randomised, placebo-controlled trial. We recruited eligible adults from rheumatology outpatient clinics at two sites in the Netherlands. Patients were considered eligible if they had symptomatic hand osteoarthritis and signs of inflammation in their distal and proximal interphalangeal (DIP/PIP) joints. For inclusion, patients were required to have four or more DIP/PIP joints with osteoarthritic nodes; at least one DIP/PIP joint with soft swelling or erythema; at least one DIP/PIP joint with a positive power Doppler signal or synovial thickening of at least grade 2 on ultrasound; and finger pain of at least 30 mm on a 100-mm visual analogue scale (VAS) that flared up during a 48-h non-steroidal anti-inflammatory drug (NSAID) washout (defined as worsening of finger pain by at least 20 mm on the VAS). Eligible patients were randomly assigned (1:1) to receive 10 mg prednisolone or placebo orally once daily for 6 weeks, followed by a 2-week tapering scheme, and a 6-week follow-up without study medication. The patients and study team were masked to treatment assignment. The primary endpoint was finger pain, assessed on a VAS, at 6 weeks in participants who had been randomly assigned to groups and attended the baseline visit. This study is registered with the Netherlands Trial Registry, number NTR5263.Findings We screened patients for enrolment between Dec 3, 2015, and May 31, 2018. Patients completed baseline visits and started treatment between Dec 14, 2015, and July 2, 2018, and the last study visit of the last patient was Oct 4, 2018. Of 149 patients assessed for eligibility, 57 (38%) patients were excluded (predominantly because they did not meet one or several inclusion criteria, most often because of an absence of synovial inflammation or of flare-ups after NSAID washout) and 92 (62%) patients were eligible for inclusion. We randomly assigned 46 (50%) patients to receive prednisolone and 46 (50%) patients to receive placebo, all of whom were included in the modified intention-to-treat analysis of the primary endpoint. 42 (91%) patients in the prednisolone group and 42 (91%) in the placebo group completed the 14-week study. The mean change between baseline and week 6 on VAS-reported finger pain was -21.5 (SD 21.7) in the prednisolone group and -5.2 (24.3) in the placebo group, with a mean between-group difference (of prednisolone vs placebo) of -16.5 (95% CI -26.1 to -6.9; p=0.0007). The number of non-serious adverse events was similar between the groups. Five serious adverse events were reported during our study: one serious adverse event in the prednisolone group (a myocardial infarction) and four serious adverse events in the placebo group (an infected traumatic leg haematoma that required surgery, bowel surgery, atrial fibrillation that required a pacemaker implantation, and symptomatic uterine myomas that required a hysterectomy). Four (4%) patients discontinued the study because of an adverse event: one (2%) patient receiving prednisolone (for a myocardial infarction) and three (7%) patients receiving placebo (for surgery of the bowel and for an infected leg haematoma and for Lyme disease arthritis of the knee).Interpretation Treatment with 10 mg prednisolone for 6 weeks is efficacious and safe for the treatment of patients with painful hand osteoarthritis and signs of inflammation. The results of our study provide clinicians with a new short-term treatment option for patients with hand osteoarthritis who report a flare-up of their disease. Copyright (C) 2019 Elsevier Ltd. All rights reserved. Show less
Kroon, F.P.B.; Bay-Jensen, A.C.; Wittoek, R.; Verbruggen, G.; Smolen, J.S.; Kloppenburg, M.; Ramonda, R. 2019
