Elsevier

The Lancet

Volume 394, Issue 10213, 30 November–6 December 2019, Pages 1993-2001
The Lancet

Articles
Results of a 6-week treatment with 10 mg prednisolone in patients with hand osteoarthritis (HOPE): a double-blind, randomised, placebo-controlled trial

https://doi.org/10.1016/S0140-6736(19)32489-4Get rights and content

Summary

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 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.

Funding

Dutch Arthritis Society.

Introduction

Around 20% of adults have osteoarthritis.1, 2 A particularly burdensome manifestation is hand osteoarthritis, which is found in 8–10% of the adult general population. The prevalence of hand osteoarthritis is 26% in women older than 70 years, and the estimated lifetime risk of the disease in the general population is 40%.2, 3, 4 A substantial burden of disease is associated with hand osteoarthritis, since the condition presents with hand pain, disability, and reduced quality of life, for which patients frequently consult health-care providers.3, 5, 6 Symptoms in the hands usually fluctuate over time, including episodes of joint swelling and erythema.7

Research in context

Evidence before this study

Hand osteoarthritis is a prevalent joint condition that causes pain, functional disability, and decreased quality of life. The clinical course of hand osteoarthritis often fluctuates, with transient flare-ups of the disease accompanied by more pain and joint inflammation. Previous evidence indicates that local joint inflammation is involved in the disease progression of osteoarthritis. A 2018 systematic literature review to update the European League for Rheumatology recommendations on the treatment of hand osteoarthritis searched MEDLINE (via PubMed), Embase, and the Cochrane CENTRAL databases for work published before June 6, 2017, and the review identified two studies of oral prednisolone. Previous trials of glucocorticoids in hand osteoarthritis were inconclusive. A trial investigating the efficacy of 5 mg prednisone daily for 4 weeks found that prednisone was not superior to placebo in reducing pain. A trial of a combined prednisolone and dipyridamole showed improvements in pain with this preparation compared with placebo but at the cost of more adverse events, particularly headaches, a known side-effect of dipyridamole. We did an updated search in PubMed for work published before March 16, 2019, and we found no new trials. We hypothesised that glucocorticoids could suppress this local inflammation and, as a result, improve signs and symptoms of hand osteoarthritis.

Added value of this study

By contrast with previous trials of glucocorticoids in hand osteoarthritis, our study investigated a potent prednisolone dosage of 10 mg daily. By specifically including patients with pain and local joint inflammation, the trial focused on patients who are most in need of treatment. In this randomised, double-blind placebo-controlled trial, we found that 6 weeks of treatment with 10 mg prednisolone daily substantially improved pain and function and imaging markers of inflammation. The large beneficial effect size exceeded that of all available therapeutic options for hand osteoarthritis, and our findings indicated that local inflammation in hand osteoarthritis can be modulated.

Implications of all the available evidence

Our study provides evidence that patients experiencing a flare-up of hand osteoarthritis can be effectively and safely treated with a 6-week course of 10 mg daily prednisolone. These findings provide clinicians with a new treatment option for a disease that that has very few therapeutic options. Finally, our study supports inflammation as a treatment target in hand osteoarthritis, which is a notable step towards targeted treatment in hand osteoarthritis, with the eventual goal of finding a treatment that can modify its disease course.

There are several therapeutic options for patients with painful hand osteoarthritis, which vary from non-pharmacological approaches, such as education and exercise, to analgesics, but their effects are modest. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for symptom relief, yet their effect is moderate at best and safety aspects restrict their use, especially in older people (those older than 65 years).8, 9, 10 Therefore, there is an unmet need for effective therapies for hand osteoarthritis.

The current treatment approach relates to the traditional idea that osteoarthritis is a degenerative disease characterised by cartilage loss and bone deformations. Accumulating evidence from the past decade suggests that osteoarthritis is a disease involving all joint compartments, in which not only mechanical triggers but also local inflammation cause pain and radiographical damage progression.1, 11, 12, 13, 14, 15, 16 Therefore, inflammation is a potential treatment target in osteoarthritis.

Glucocorticoids are potent multitargeted anti-inflammatory drugs, and we therefore hypothesised that signs and symptoms in patients with hand osteoarthritis would improve by suppressing local inflammation with glucocorticoids.

We aimed to investigate the clinical efficacy and safety of short-term treatment with the glucocorticoid prednisolone in patients with painful hand osteoarthritis who had evidence of synovial inflammation.

Section snippets

Study design and participants

The Hand Osteoarthritis Prednisolone Efficacy (HOPE) study is a double-blind, randomised, placebo-controlled trial. We recruited eligible adults from rheumatology outpatient clinics at two sites in the Netherlands (appendix p 1). Patients were considered eligible if they had symptomatic hand osteoarthritis that fulfilled the American College of Rheumatology criteria11 and if they had signs of inflammation in their distal and proximal interphalangeal (DIP/PIP) joints. For inclusion, patients

Results

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 their 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%)

Discussion

In this double-blind, randomised, placebo-controlled trial of prednisolone in patients with painful hand osteoarthritis and signs of synovial inflammation, we found that 6 weeks of treatment with 10 mg prednisolone led to a substantial reduction in finger pain. Prednisolone was consistently better than placebo in secondary outcome measures of pain and function, with a large difference in the proportion of OMERACT-OARSI responders between groups (72% vs 33%). MRI and ultrasound measures also

Data sharing

Requests for data collected in the HOPE study (such as deidentified participant data) can be made to the corresponding author following publication, and requests will be considered on an individual basis. The study protocol with amendments and statistical analysis plan are available in the appendix (pp 11–51).

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