The Efficacy and Safety of Intramuscular Methylprednisolone in Patients With Hand OsteoArthritis

The primary objective of this study is to assess the efficacy of intramuscular methylprednisolone acetate (120mg or 40mg) in reducing hand pain between baseline and week 4, compared to placebo measured on a digital Visual Analogue Scale ranging from 1-100 mm. The higher the score, the worse the outcome.

Investigate non-inferiority of 40mg MP compared to 120mg MP (in case superiority to placebo of both interventions is proven in the primary analysis) of the efficacy of intramuscular methylprednisolone acetate in reducing hand pain measured on a digital Visual Analogue Scale ranging from 1-100 mm. The higher the score, the worse the outcome.

Compare the three treatment arms based on change in hand pain at week 8, and therafter every 4 weeks until week 48 measured on a digital Visual Analogue Scale ranging from 1-100 mm. The higher the score, the worse the outcome.

Compare the three treatment arms based on percentage of participants with a reduction in hand pain larger than the minimal clinically important difference in pain (MCID) = 10 mm

Compare the three treatment arms based on hand function. Change in functional index for hand OA at week 4, 16, 32 and 48, compared to baseline measured with Michigan Hand outcomes Questionnaire ranging from 0-100. The higher the score, the better the hand function.

Compare the three treatment arms based on OMERACT-OARSI responder criteria based on pain measured on a digital Visual Analogue Scale ranging from 1-100 mm. The higher the score, the worse the outcome. Proportion participants fulfilling responder criteria every 4 weeks compared to baseline.

Compare the three treatment arms based on OMERACT-OARSI responder criteria based on hand function measured on a digital Visual Analogue Scale ranging from 1-100 mm. The higher the score, the worse the outcome. Proportion participants fulfilling responder criteria every 4 weeks compared to baseline.

Compare the three treatment arms based on OMERACT-OARSI responder criteria based on patient global assessment measured on a digital Visual Analogue Scale ranging from 1-100 mm. The higher the score, the worse the outcome. Proportion participants fulfilling responder criteria every 4 weeks compared to baseline.

Compare the three treatment arms based on Quality of Life, measured with EuroQuol-5D-5L questionnaire at week 16, 32 and 48.

The EuroQol EQ-5D-5L has two measurement systems: the health state index score and the EQ Visual Analogue Scale (EQ VAS). The health state index score ranges from below zero to 1, with 1 being full health and values below zero indicating a state worse than death, depending on the specific country's value set. The EQ VAS, which measures current overall health, ranges from 0 to 100, where 100 is the best imaginable health

Compare the three treatment arms based on patient experience of steroid use with the Steroid PRO questionnaire every 4 weeks. Answers can be ranged from 1 to 5. Where the higher the score, the worse the outcome.

Compare the three treatment arms based on changes in local inflammation of the hand joints, determined with Ultrasound (US). US of hands to assess change in DIP/PIP joints at week 4 compared to baseline with change in power doppler and Greyscale score. Scores of effusion, proliferation, osteophytes and power doppler are scored between 0 to 3, where the higher the score, the worse the outcome.

Compare the three treatment arms based on structural changes based on X-ray of the hands to determine joint space narrowing, erosive or non-erosive, DIP/PIP joints and osteophytes between baseline and 48 weeks follow-up.

Compare the three treatment arms based on effect on affected joints based on swollen joint count (SJC) and tender joint count (TJC) at baseline, week 4 and week 48.

Compare the three treatment arms based on changes of systemic inflammation assessed by C-reactive protein (CRP) at week 4, 16, and 48 compared to baseline. This is scored as: normal levels being less than 10 mg/L or less than 1 mg/dL. Mild elevations (10-40 mg/L) often indicate mild infection or chronic conditions, while high levels (>40 mg/L) suggest more significant inflammation, acute bacterial infection, or autoimmune disease.

Compare the three treatment arms based on changes of systemic inflammation assessed by Erythrocyte Sedimentation Rate (ESR) at week 4, 16, and 48 compared to baseline. ESR can be measured in range from 0 to high levels (above 100) mm/hour. The higher the value, the worse the outcome.

Compare the three treatment arms based on medication use, health care use and costs by using the iMTA Productivity Cost Questionnaire (iPCQ). It measures health-related productivity losses in the form of monetary values rather than standard units of measurement. It collects data on absenteeism and presenteeism in paid work and productivity loss in unpaid work, which is then used to calculate productivity costs in a currency.

Compare the three treatment arms based on medication use, health care use and costs by using the iMTA Medical Consumption Questionnaire (iMCQ). The iMCQ is an instrument for measuring medical consumption. The iMCQ includes questions related to frequently occurring contacts with health care providers.

Correlation between baseline clinical and imaging measures - pain severity (VAS, 0-100 mm), hand function (VAS score, 0-100 mm), grip strength (kg, dynamometer), and synovitis (ultrasound, 0-3 scale) - and treatment response, defined by the OMERACT-OARSI responder criteria (% of patients classified as responders). Statistical analysis: correlation/regression and development of a multivariable prediction model.

Explore subgroups according to structural changes on X-ray of the hand based on erosive or non-erosive, DIP osteophytes or PIP osteophytes, DIP joint space narrowing or PIP joint space narrowing at baseline.

Assess the safety of methylprednisolone 120mg or 40mg compared to placebo by assessing incidence density and cumulative incidence of all AEs and SAEs and (S)AEs related to glucocorticoid use for each phase, using the Common Terminology Criteria for Adverse Events version 5 (CTCAEv5) and using the Glucocorticoid Toxicity Index (GTI) light.

Evaluate efficacy and safety of methylprednisolone on endpoints mentioned under 2 and 3, comparing participants based on the cumulative dose of MP received during the study period.

Explore subgroup differences categorized by demographic factors

Explore subgroup differences categorized by X-ray measured by joint space narrowing, osteophytes and symptom structure concordance

Explore subgroup differences categorized by ultrasound measured by osteophytes, effusion and proliferation in DIP and PIP joints

Explore subgroup differences categorized by biomarkers in blood. Biomarkers are still unknown, and will be established during experiments.

Identification of circulating biomarkers associated with response to MP. Circulating biomarkers are still unknown and will be evaluated during experiments.