Efficacy and safety of non-pharmacological, pharmacological and surgical treatments for hand osteoarthritis in 2024: a systematic review
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Abstract
Background We aimed to update the 2018 systematic literature review on the efficacy and safety of treatments for hand osteoarthritis (OA), which was based on 126 studies.
Methods We performed a systematic literature search on randomised controlled trials from June 2017 up to 31 December 2023. Risk of bias was assessed using the RoB2 tool. Meta-analyses of previous and new studies regarding the efficacy for pain, function, grip strength and OMERACT/OARSI responders were performed. Certainty of evidence was judged using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) tool.
Results Sixty-five new studies were included. For non-pharmacological interventions, there was low-certainty evidence for a small long-term effect of hand exercises and a moderate long-term effect of thumb orthoses for pain, and moderate-certainty evidence that assistive devices had a moderate long-term effect on function. Concerning pharmacological interventions, there was low-certainty evidence for a moderate short-term effect of oral non-steroidal anti-inflammatory drugs (NSAIDs) on pain, high- and moderate-certainty evidence for a small short-term effect of topical NSAIDs and oral glucocorticoids on function, respectively, and low-certainty evidence that oral glucocorticoids had a small short-term effect on function. Further, there was low-certainty evidence that methotrexate had a small long-term effect on pain. The heterogeneity of studies did not allow for any meta-analyses on surgery.
Conclusion The results largely support current treatment recommendations. However, there is a lack of interventions that efficiently improve grip strength, and the evidence for most current treatments is still limited. To better understand action mechanism of different treatments, future trials should include hand OA subtyping and be powered for subgroup analyses.
What is already known on this topic
Hand osteoarthritis (OA) is a prevalent rheumatic joint disease, for which there is yet no cure or disease-modifying treatment.
There is a general consensus across international treatment recommendations that all patients with hand OA should receive patient education and exercises to improve hand function, that topical or oral non-steroidal anti-inflammatory medication may be considered for short time use, whereas surgery may be considered for patients with structural abnormalities when other treatment modalities have not been sufficiently effective in relieving pain.
The treatment recommendations vary with respect to other treatment modalities, and the evidence for most treatments is limited.
What this study adds
This systematic literature review includes 65 new randomised controlled trials published in the hand OA field since June 2017, thereby providing an updated overview of all current evidence on efficacy and safety of non-pharmacological, pharmacological and surgical treatment options for hand OA.
How this study might affect research, practice or policy
This study confirms the need for high-quality randomised controlled trials including hand OA subtyping to better understand the action mechanisms and allow for separate analyses with regard to OA phenotype and trials with low risk of bias.
It further shows that there is a need for studies that help us understand factors that may influence grip strength as a basis for developing evidence-based interventions that efficiently improves grip strength.
The results also indicate that mobile applications may be used to deliver interventions designed to enhance self-management, but the efficacy and cost-effectiveness of this delivery mode should be evaluated in robust clinical trials.
Introduction
Hand osteoarthritis (OA) is a common rheumatic joint disease, leading to structural and functional impairment that may significantly impact body functions and structures, activity performance, work ability and health-related quality of life.1 2 Despite its high and increasing prevalence, research shows that the quality of care services in general is suboptimal for people with OA, and that especially those with hand OA have poor access to treatment in primary and specialist healthcare.3 4 To optimise the care for people with hand OA, treatment recommendations should be based on updated best evidence.
In a recent systematic review, Conley et al identified the following four high-quality clinical guidelines published since 2019, addressing different treatments for hand OA5: The OsteoArthritis Research Society International (OARSI) guidelines for the non-surgical management of knee, hip and polyarticular OA6; the 2019 American College of Rheumatology (ACR)/Arthritis Foundation Guideline for the Management of OA of the Hand, Hip, and Knee7; the Italian Society for Rheumatology clinical practice guidelines for the diagnosis and management of knee, hip and hand OA8; and the 2018 update of the European Alliance of Associations for Rheumatology (EULAR) recommendations for the management of hand OA.9 After the review by Conley et al was published,5 the National Institute for Health and Care Excellence (NICE) has also launched updated guidelines for diagnosis and management of OA, including hand OA.10 There is a general consensus across the five guidelines that patient education and exercises are essential components of hand OA treatment, that topical non-steroidal anti-inflammatory drug (NSAID) gel/cream should be the first pharmacological choice, and that oral NSAIDs may be considered alongside non-pharmacological treatment for short time use. Further, EULAR and ACR guidelines state that conventional or biological disease-modifying anti-rheumatic drugs (DMARDs) should not be used in hand OA. However, the treatment recommendations vary with respect to other treatment modalities, such as the use of orthoses, assistive devices, electrotherapy, thermal modalities, paracetamol and intra-articular injections. The aim of the current study was to update the 2018 systematic literature review (SLR) by Kroon et al11 on the efficacy and safety of non-pharmacological, pharmacological and surgical treatments for hand OA.
Methods
Search strategy
The study protocol for this review have been published in the International Prospective Register of Systematic Reviews, PROSPERO (#CRD42022288691). A systematic literature search was conducted by two of the authors (ATT and IK) in close collaboration with an experienced librarian. We used the same search strategy as Kroon et al (see online supplemental material) and searched the PubMed/MEDLINE, Embase and Cochrane CENTRAL databases from 7 June 2017 (end date of search of original SLR) up to 31 December 2023. Additionally, conference abstracts of the EULAR, ACR and OARSI annual conferences of 2022 and 2023 and EULAR, and reference lists of included studies and other relevant SLRs were screened. Eligible study types were parallel randomised controlled trials (RCTs), cluster-randomised trials and cross-over randomised trials, published in English or Scandinavian. Cochrane systematic reviews were also included as a source of relevant RCTs.
We included all studies of non-pharmacological, pharmacological and surgical interventions for hand OA. Additionally, studies also involving participants with other diagnoses were included if the results were presented separately for participants with hand OA.
In line with the outcomes proposed by the OMERACT core set,12 the main efficacy outcomes were as follows: (1) pain (measured on Visual Analogue Scale (VAS)), Numerical Rating Scale (NRS) or a validated questionnaire, for example, Australian/Canadian Hand OA Index (AUSCAN) or Michigan Hand Outcomes Questionnaire (MHQ); (2) hand function measured by a validated questionnaire, for example, Functional Index for Hand OA (FIHOA), AUSCAN or MHQ; (3) grip strength; and (4) number of participants fulfilling the OMERACT-OARSI responder criteria.13 Safety measures (adverse events (AEs)) were also analysed, if available.
Study selection, data extraction, risk of bias and GRADE assessment
Four reviewers (ATT/DHB/KAAF/IK, working in pairs) screened all titles and abstracts using the Rayyan tool.14 The following hierarchy was used for exclusion:
Wrong design.
Wrong population.
Wrong language.
Wrong intervention.
Wrong outcome.
In case of doubt, the third reviewer was consulted. Thereafter, potentially relevant studies were read and evaluated in full text. For each study, two authors (DHB/IS/IK) extracted data on study design, first author, publication year, patients (hand OA definition, location and subtype, proportion of women, mean age, disease duration, number of participants per study arm), intervention (including frequency, duration and dose), primary outcome, other outcomes and AEs. The data extraction sheets were subsequently compared to ensure accuracy.
Risk of bias (RoB) was assessed in pairs by three authors (DHB, IS and IK) using the RoB2 tool,15 including bias arising from the randomisation process, deviations from the intended interventions, missing outcome data, measurement of the outcome and selection of the reported results. Each item was judged as low (green colour), high (red) or some concerns (yellow). Finally, we did an ‘overall assessment’ for each study based on the judgements of all RoB2 items. Although not described in the protocol, we decided to also use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool to assess the certainty of the effect estimates of all interventions and outcomes for which we conducted a meta-analysis.16 One author (GS) performed a first assessment, which was thereafter checked by two other authors (DHB, IK). GRADE considers the risk of bias, consistency and directness of estimates, precision of results, risk of publication bias, size of effect, dose-response, and possible confounding to produce a grading into one of four categories: high-, moderate-, low- or very low-certainty of the estimates of the efficacy. In section 6 in the online supplemental material, we show GRADE summary of findings tables for each outcome. Whenever we have downgraded the certainty, the reasons for this downgrading are provided in the footnote.
Data analysis
We extracted outcome data from each study and, as in the original review,11 categorised these by short-term (<3 months) and long-term (≥3 months) follow-up. Continuous outcomes were summarised as standardised mean differences (SMDs) with 95% CIs. We used random-effects models for conducting meta-analyses of studies assessing efficacy of the same intervention and pooled data if there was adequate clinical and methodological homogeneity. Heterogeneity was assessed with the I² statistic and tested with Cochran’s Q test. However, we only pooled data from studies where the intervention of interest was compared with a control group receiving placebo or no intervention, or, if study groups received a combination of interventions, the only difference between groups in terms of treatment was the intervention of interest. We also included results from relevant studies in the SLR by Kroon et al11 in the meta-analyses (hereafter termed previous studies), but used data from full-text articles of conference abstracts included in this SLR, if available.17–23
We applied the commonly used categorisation by Cohen, and regarded the effect as small, moderate or large if the SMD was 0.2–0.5, ≥0.5–0.8 and ≥0.8, respectively.24 Finally, we conducted meta-analyses comparing the pooled effect of each non-pharmacological and pharmacological intervention on the four main efficacy outcomes. The Stata Statistical Software: Release V.18 was used for meta-analyses.
Results
After removal of duplicates, the SLR yielded a total of 4162 records, of which 65 studies (hereafter termed new studies) reported in 66 publications were included (see flow chart in the online supplemental material, p 6). Thirty-three studies (reported in 34 articles) assessed benefits and harms of different non-pharmacological therapies, 17 investigated pharmacological interventions against each other or placebo, 4 studies compared pharmacological and non-pharmacological interventions, whereas different surgical interventions were compared in 10 studies. Additionally, one study with three arms compared a non-pharmacological and a pharmacological intervention to a control group receiving no intervention25 and is listed both as a non-pharmacological and a pharmacological intervention. We did not identify any new relevant Cochrane reviews. The characteristics and overall RoB of all new studies are presented in tables 1–3. The detailed RoB of all new studies are provided in online supplemental material (pp 10–26), as are characteristics and overall RoB of previous studies included in our meta-analyses (pp 27–36), GRADE assessments of the meta-analyses with reasons for why an analysis was downgraded (pp 37–52) and the meta-analyses (pp 53–89). The main results of the GRADE assessments are also included in figures 1–3. The reporting of results mainly focuses on findings new to this review, meta-analyses where results are graded with moderate or high-certainty, and on efficacy and safety of interventions recommended for or against in one or more of the five hand OA guidelines.6–9
Table 1
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Characteristics of 34 new studies of non-pharmacological interventions published between 7 June 2017 and 31 December 2023
Table 2
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Characteristics of 22 new studies of pharmacological interventions published between 7 June 2017 and 31 December 2023
Table 3
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Characteristics of 10 new studies surgical interventions (published between 7 June 2017 and 31 December 2023)
Effect of non-pharmacological and pharmacological interventions on pain. The GRADE assessment is provided in brackets after description of each intervention. CMC-orthoses immobilise the CMC-joint only, whereas MCP-orthoses additionally immobilises the MCP and/or wrist. bDMARDs, biological disease-modifying anti-rheumatic drugs; GRADE, Grading of Recommendations Assessment, Development and Evaluation; MCP,metacarpophalangeal; NSAID, non-steroidal anti-inflammatory drug; SMD, standardised mean difference.
Effect of non-pharmacological and pharmacological interventions on function. The GRADE assessment is provided in brackets after description of each intervention. CMC-orthoses immobilise the CMC-joint only, whereas MCP-orthoses additionally immobilises the MCP and/or wrist. CMC, first carpometacarpal joint; GRADE, Grading of Recommendations Assessment, Development and Evaluation; MCP, metacarpophalangeal; NSAIDs, non-steroidal anti-inflammatory drugs; SMD, standardised mean difference.
Effect of non-pharmacological and pharmacological interventions on grip strength. GRADE assessment is provided in brackets after description of each intervention. GRADE, Grading of Recommendations Assessment, Development and Evaluation; SMD, standardised mean difference.
Non-pharmacological interventions
We identified 34 new studies assessing the efficacy of exercises (n=11), orthoses (n=6), assistive devices (n=1), kinesiology tape (n=2), thermal modalities (heat application) (n=7), ultrasound/laser therapy (n=1), low-dose radiation therapy (n=1, results reported in two articles), gloves (n=1), acupuncture (n=1) or programmes combining two or more non-pharmacological interventions (n=3) (table 1). The studies varied with regard to number of participants (11–347; 11 studies with ≥80 participants), type and duration of interventions (range 1–24 weeks, the majority ≤8 weeks), outcomes included and follow-up period (4–52 weeks). None of the studies specifically included participants with signs of inflammatory OA. All but two studies26 27 were parallel RCTs, and all but one study on low-dose radiation therapy28 were judged to have high RoB or some concerns, most often related to lack of blinding of participants and therapists delivering the interventions (online supplemental material, pp 10–18). Whereas the studies on ultrasound/laser, radiation, acupuncture and one study of thumb orthoses29 used placebo as comparator, the control group in the other studies either received no intervention, an information leaflet, the same intervention as the intervention group except for the intervention of interest, or another intervention (see also descriptions in table 1). All the results from our meta-analyses were graded with very low or low certainty, except for one on long-term effect of assistive devices on function and one on short-term effect of ultrasound/laser on grip strength, which both were graded as moderate certainty.
Hand exercises
Six of 11 new exercise studies evaluated the effect of hand exercises (see table 1 for details on interventions).26 30–34 The exercise programmes varied in content, length and intensity and were often combined with other non-pharmacological interventions. Meta-analyses of four new26 30–32 and five previous studies21 35–38 showed that, compared with no exercises, there is low-certainty evidence of a significant small long-term effect of exercises on pain (SMD=−0.34 (–0.58, –0.09)). For the other outcomes (function, grip strength and number of OMERACT/OARSI responders), the certainty of results from meta-analyses was very low (online supplemental material, pp 37, 53–56). New to this SLR, we also identified five studies assessing the effect of adding proprioceptive exercises to other hand exercise programmes.39–43 We pooled four of these studies,39–41 43 but again the certainty of results from meta-analyses was very low (online supplemental material, pp 38, 57–58). None of the new exercise studies reported on AEs, whereas Kroon et al11 reported few and non-severe AEs in participants undergoing exercise therapy.
Orthoses
We identified six new studies on orthoses. One was a trial with high RoB showing that a custom-made night-time orthosis for the distal (DIP) and proximal interphalangeal (PIP) joint of the second or third finger of the dominant hand had no effect on pain or function compared with no orthosis.44 Two studies investigated the effect of a thumb orthosis against a placebo orthosis29 or information only.45 When pooling these two with five previous studies,46–50 the results from meta-analyses showed that there is low-certainty evidence that, compared with no orthoses, thumb orthoses has a significant and moderate long-term effect on pain (SMD = –0.77 (– 1.20, –0.34)) (online supplemental material, pp 39, 59–62). The last three new studies compared thumb orthoses immobilising the first carpometacarpal (CMC-1) joint against thumb orthoses additionally immobilising the wrist and/or one or more thumb joints.27 51 52 The certainty of results from meta-analyses of these and four previous studies22 53–55 was very low for all outcomes (pain and function) (online supplemental material, pp 40, 63–64). One new29 and two previous22 50 studies reported on AEs, which were few and none serious.
Assistive devices
We identified one new study on the effect of assistive devices,56 and pooled this with one previous study.57 Compared with no assistive devices, the results showed evidence of moderate certainty for a moderate long-term effect of assistive devices on hand function (SMD −0.55, CI (−0.94 to –0.16)) (online supplemental material, pp 41, 65–66).
Thermal modalities
Five new studies evaluated the effect of heat application. The interventions comprised hot paraffin,58–60 hot mud,58 61 hot compress25 and/or dry heat therapy60 against each other or placebo. The results of meta-analyses of three new25 59 62 and five previous studies20 63–66 showed that, compared with no heat application, there is evidence for a large, significant short-term and long-term effect on pain, and a moderate, significant long-term effect on function; however, these results were graded with very low certainty (online supplemental material, pp 42, 67–69).
Ultrasound/laser therapy
One new study evaluated the effect of high-intensity laser therapy67 and were pooled with results from two previous studies.35 68 The results shows that, compared with a sham intervention, there is possibly small or no long-term effects on grip strength (SMD −0.13 (−0.50, 0.24) (low certainty)) (online supplemental material, pp 43, 70–71).
Combination programmes
We identified three new studies of combination programmes. One of these, and so far the first study of mobile health (mHealth) strategies, compared a mobile app-delivered multimodal programme with a control group receiving written exercises, and had a high RoB.69 The results showed significant differences in short-term and long-term pain and in long-term upper-limb function in favour of the mobile-app delivered programme. No serious AEs were registered.
The two other new studies compared a combination programme with routine care+placebo (a massage ball)70 or information only.71 When pooling these with three previous studies,35 72 73 the certainty of the results was very low for all outcomes of pain, function or grip strength. Two previous studies reported on AEs,72 73 which were few, mild and with no significant between-group differences (pp 44, 72–74).
Pharmacological interventions
An overview of the characteristics and overall RoB of the 21 new studies including a pharmacological intervention is presented in table 2. All were parallel RCTs, of which 3 compared different pharmacological interventions against each other,74–76 14 investigated pharmacological interventions against placebo,77–90 and 4 compared combination programmes that also included a pharmacological intervention.91–94 The studies varied with regard to number of participants (16–204; 10 studies with ≥80 participants), 16 lasted ≥3 months, and 3 specifically included participants with signs of inflammatory OA (investigating oral glucocorticoids80 or DMARDs).83 84 Eight studies had low RoB. Reasons to judge studies to be at high (n=9) or unclear RoB (n=5) were most often related to the randomisation process, outcome measurement and/or selective reporting. Two meta-analyses were graded with high certainty, two with moderate and the rest with low or very low certainty. The detailed RoB and GRADE assessment are presented in online supplemental material (pp. 19–24, 45–52).
Topical pharmacological interventions
We identified one new study with 106 participants and low RoB comparing a topical corticosteroid ointment to placebo.79 The results showed no significant between-group differences in any measure of pain or function after 6 weeks of treatment, and comparable rates of AEs between groups.
No new studies assessed the effect of topical NSAIDs. Meta-analyses of three previous studies comparing diclofenac95 96 or ibuprofen cream97 to placebo showed a very small significant between-group difference in short-term function in favour of topical NSAIDs (SMD −0.17 (–0.33, –0.01), high certainty), and possibly a small or no short-term effect on pain (SMD −0.07 (−0.37, 0.24), low certainty) (online supplemental material, pp 45, 75).
Oral NSAIDs
No new studies of oral NSAIDs were detected. A meta-analysis of three previous studies comparing ibuprofen,98 lumiracoxib99 or meclofenamate100 to placebo showed that there were possibly a moderate effect on short-term pain (SMD −0.59 (−1.07, –0.11), low certainty), and no significant between-group differences in any measure of adverse events (low, moderate or high certainty) (online supplemental material, pp 46, 76–78).
Oral glucocorticoids
We identified one new study of oral glucocorticoids,80 which we pooled with two previous studies.101 102 The results showed that, compared with placebo, oral glucocorticoids likely had a small significant effect on short-term function (SMD −0.35 (−0.64, –0.07), moderate certainty), and possible a small or no effect on long-term function (SMD −0.11 (−0.58, 0.37), low certainty). Further, there is possibly a large to no effect on short-term pain (SMD −1.44 (−3.63, 0.74), very low certainty) and a small to no effect on long-term pain (SMD 0.12 (−0.36, 0.59), low certainty) (online supplemental material, pp 47, 79–80).
Intra-articular injections
We did not detect any new studies assessing the effect of intra-articular (IA) glucocorticoids or hyaluronic acid injections against placebo. We performed meta-analyses of three previous studies assessing glucocorticoid injections,103–105 showing no between-group differences in long-term pain (SMD −0.17 (−0.69, 0.35) or all AEs. However, the results were of very low certainty (online supplemental material, pp 48 and 81).
bDMARDs/TNF inhibitors
We identified three new studies comparing the effect of subcutaneous lutikizumab injections (anti-IL-1α/β)9; intravenous tocilizumab infusions (anti-IL-6)82; or subcutaneous otilimab injections (anti-GM-CSF)83 to placebo. There were no significant between-group differences in any clinical outcome in any of the three studies, whereas AEs were more frequent in the intervention groups compared with placebo groups. We pooled results from four previous studies on adalimumab18 106 107 or etanercept (anti-TNF).17 The results showed that, compared with placebo, there is evidence of very low certainty for no effect on long-term pain (−0.04 (−0.38, 0.30)) and of moderate certainty for no between-group differences in all AEs (RR 0.95 (0.79, 1.15)) (online supplemental material, pp 49, 82–83).
Synthetic DMARDs
One new study on the effect of oral hydroxychloroquine84 was detected and pooled with two previous studies.19 23 The results from meta-analyses showed that, compared with placebo, there is low and moderate certainty for no effect on short-term or long-term pain ((0.08 (−0.2, 0.36)) and (0.01 (−0.18, 0.16)), respectively, and of very low certainty for any effect on long-term function (SMD −0.03 (−0.24, 0.18)) or all AEs (online supplemental material, pp. 50, 84–85). New to this SLR, we also detected and pooled results from two studies on the effect of methotrexate against placebo.85 86 There is possibly a small effect on long-term pain (SMD −0.31 (−0.61, 0.00), low certainty) and long-term function (SMD −0.17 (−0.49, 0.15), low certainty), and very low certainty evidence for an effect on all adverse events (RR 0.80 (0.37, 1.73)) (online supplemental material, pp 51, 86–87).
Colchicine
New to this review, we detected and pooled two studies comparing colchicine to placebo.88 108 The results show that colchicine is not superior to placebo in terms of efficacy, while there is likely a higher risk of adverse events (RR 1.70 (1.27, 2.28), moderate certainty). The certainty for the results regarding pain, function and grip strength was very low (online supplemental material, pp 52, 87–89).
Surgical interventions
We identified nine new studies of surgical interventions109–117 and one118 reporting the 17-year follow-up results of a trial also included in the review by Kroon et al (see table 3). All studies were parallel RCTs. No trials compared surgery to no surgery, sham surgery or non-surgical interventions. All but one study109 were judged to have high RoB or some concerns (online supplemental material, pp 25–26). Due to the heterogeneity of new and previous studies, we did not perform any meta-analyses of efficacy. New to this SLR, four studies compared joint replacement to trapeziectomy with or without ligament reconstruction and tendon interposition.109–112 In three of the studies,110–112 the participants treated with prosthesis improved faster; however, after 6–12 months, there were no significant differences between the two groups. In the fourth study,109 which was the only study with low RoB, those receiving prothesis had significantly better grip strength and range of motion after 12 months compared with those treated with trapeziectomy.
The other six trials compared trapeziectomy performed with different or additional surgical techniques or interventions. In general, there were no significant between-group differences in any measure of pain, function or grip strength in any of the studies.
The efficacy of various treatments with regard to outcome
In a final step, we combined the results from the meta-analyses described above to visualise the efficacy of the different non-pharmacological and pharmacological treatments on pain, function and grip strength. As visualised in figure 1, there is evidence of moderate certainty that hydroxychloroquine has no long-term effect on pain, and evidence of low certainty that hand exercises may have a small long-term effect, hand orthoses a moderate long-term effect, oral NSAIDs a moderate short-time effect, and methotrexate a small long-term effect on pain.
With regard to function (figure 2), there is high-certainty evidence for a very small short-term effect of topical NSAIDs, moderate-certainty evidence for a moderate long-term effect of assistive devices and a small short-term effect of oral glucocorticoids, and low-certainty evidence for a small long-term effect of exercises and a moderate effect of thermal modalities. Lastly, there is moderate-certainty evidence that hand ultrasound/laser has no effect on grip strength.
Discussion
The aim of this SLR was to summarise the evidence for efficacy and safety of non-pharmacological, pharmacological, and surgical treatments for hand OA. In line with the current guidelines,6–10 recommending non-pharmacological interventions as the first choice of intervention, we found moderate-certainty or low-certainty evidence of the efficacy of hand exercises, thumb orthoses and use of assistive devices for pain and/or function. In the few studies which collected data on AEs, the reported AEs were infrequent and mild, indicating that these interventions are safe.
Research has demonstrated that the reduced grip strength of people with hand OA negatively impacts their function.119 120 Even if the exercise programmes varied in the type and number of exercises, as well as in the intensity, duration and frequency of sessions per day and week, most programmes included strengthening exercises. The meta-analyses showed a moderate estimated effect on grip strength; however, this evidence was of very low certainty. To improve the quality of these programmes, a key next step is to design an exercise programme based on current evidence and recommendations, and evaluate its effect in studies with a sufficient number of participants. Future studies should also monitor adherence, as it is crucial for achieving any meaningful effect. Moreover, to develop more effective interventions, it is essential to conduct research that deepens our understanding of the factors influencing grip strength.
The development of mobile health devices (mHealth) represents a paradigm shift in healthcare, enhancing the delivery of evidence-based and sustainable care. However, to date, there are few mobile applications with programmes specifically developed for people with hand OA.121 Interestingly, results from the study comparing home exercise therapy delivered via a mobile application or on paper suggest that the app-based approach has at least the same efficacy as the traditional paper method. This indicates that mobile applications can serve as a viable and feasible mode of treatment delivery.69 However, further research is warranted to understand the full impact of mHealth for people with hand OA, including high-quality trials evaluating the efficacy and cost-effectiveness of this delivery mode.
We found that thumb orthoses possibly had a moderate long-term effect on pain. Thumb orthoses are, however, not included in the updated NICE guidelines,10 most likely due to a recent large placebo-controlled RCT showing no additional benefit after 8 and 12 weeks of adding a thumb orthosis to a self-management programme for CMC-OA.29 However, among the RCTs on thumb orthoses included in our SLR, only the two studies with follow-up ≥6 months48 50 suggested a notable decrease in pain within the intervention group, thereby supporting the EULAR recommendation advocating long-term use when CMC-orthoses are indicated.9 Also, to better decipher which thumb orthoses works best for whom, studies linking design to hypothesised working mechanisms and evaluating long-term effects of such orthoses are needed.
Although the results from meta-analyses were graded with very low certainty, we found that thermal interventions in general was beneficial. This is a low-cost and probably safe intervention which often is included at the beginning of exercise programmes to warm up the hands.122 Also, in line with results from a study on patients with rheumatoid arthritis,123 one of the new RCTs showed that hot wax bath followed by hand exercises resulted in significant short term improvements in pain, function and grip strength compared with hand exercises only.59 However, high-quality studies are needed to decide if a warm-up exercise should be included in future exercise programmes.
Looking at pharmacological interventions, there was high-certainty evidence for a small short-term effect of topical NSAIDs on function, low-certainty evidence for a moderate short-term effect of oral NSAIDs on pain, moderate-certainty evidence for a small short-term effect of oral glucocorticoids on function and low-certainty evidence for a small long-term effect of methotrexate on pain. Considering the lack of any convincing pain-relieving effects of topical NSAIDs, one might question the consensus across several guidelines that this should be the first choice when it comes to medication. However, as stated in the EULAR recommendations,9 the recommendation also takes into consideration the beneficial effect on function and the favourable safety profile compared with oral analgesics, making it a safe choice. Further, the lack of evidence on any effect of IA corticoid injections, biological DMARDs and hydroxychloroquine strengthens the recommendations against the use of such medication.
New to this SLR, we identified two studies evaluating the effect of methotrexate in patients with symptomatic hand OA.85 86 The meta-analyses showed that there is low-certainty evidence for a small long term-effect on pain and no effect on function, indicating that further research is needed to clarify the role methotrexate may have in the treatment of hand OA. Interestingly, the most recent of the two studies86 is the only study in this SLR applying synovitis detected by MRI as an inclusion criterion. Research has shown that the presence of synovitis is consistently associated with joint pain and structural progression.124 Hand OA subtyping should therefore be included in all future studies to better understand the mechanism of action.
As in the review by Kroon et al,11 the large heterogeneity and lack of control groups prevented us from doing any meta-analyses of surgical studies, and thus, no conclusions regarding which interventions may be effective can be drawn. Nevertheless, in an RCT investigating whether occupational therapy in the waiting period before surgical consultation for CMC-OA could reduce the likelihood of surgery, there were no significant differences after 2 years in pain or hand function between those opting for surgery and those who did not.125 Interestingly, surgery did not result in additional improvements in pain and hand function within the group that received occupational therapy. To establish an evidence-based practice, it is now time for surgery to be compared with non-surgical treatments or placebo in robust RCTs, instead of comparing a variety of surgical interventions to each other.
A positive finding in this SLR is a significant increase in RCTs investigating the efficacy of treatments for hand OA. The first EULAR recommendations, published in 2007, were based on 48 RCTs or CTs.126 Seventy-five studies were added to the evidence-base for the updated recommendations in 2018,11 whereas we detected 65 new RCTs published up to 2024, suggesting a growing interest in hand OA research. On the negative side is the fact that the majority of studies included rather few participants. Additionally, in most of the non-pharmacological studies, the context varies, seemingly identical treatments often differ in design and content, and blinding of participants and therapists is usually not possible. Overall, this means that the studies have a high risk of systematic biases, indicating that the evidence base for hand OA treatments still is rather weak.
A limitation of the current SLR is that we have pooled results from studies comparing programmes with different content, and studies with different medication dosage. The large number of meta-analyses also required numerous decisions, which can lead to either overestimation or underestimation of the true effects of interventions. Moreover, combining pilot or feasibility studies with full-scale studies in these meta-analyses may have inflated the observed effects.127 Additionally, restricting the review to RCTs may limit the generalisability of the findings, as the effects observed under controlled conditions may differ from those in real-world clinical settings, where there is greater variability among patients and clinicians. Still, we probably have included a mixture of studies examining efficacy (referring to studies performed under ideal or controlled conditions) and effectiveness (studies assessing the effect under more ‘real world’ clinical settings). However, even if these two concepts may be easy to distinguish between in theory, in practice, they represent a continuum. As a result, we did not attempt to differentiate between them in this SLR. Readers should also be aware that effect estimates of results from the studies (as visualised in figures 1–3) are not directly comparable due to clinical heterogeneity of the study populations and differences in risk of bias. Further, as we included studies with high RoB in meta-analyses and conducted GRADE assessments, our results sometimes differ from those in Kroon’s review. Also, defining a timeframe of 3 months or more as ‘long-term’ may limit the relevance of these results for informing clinical practice and policy. Lastly, the possibility of missing relevant publications cannot be entirely excluded. However, the strengths include an extensive literature search, independent study and data extraction by two authors, and thorough RoB and GRADE assessments to evaluate the certainty of the evidence.
Conclusions
The results from this SLR largely support current treatment recommendations. However, the evidence for most current treatments is still limited, particularly a lack of interventions that efficiently improve grip strength and of studies comparing non-pharmacological or surgical interventions to placebo or no intervention. To better understand the action mechanisms, future trials should include hand OA subtyping and be powered for subgroup analyses.
Contributors: IK, ATT, NØ and GS conceived and designed the study and contributed to the development of the protocol. ATT and IK developed the search strategy. ATT, DHB, IS, KAAF and IK sorted the references and extracted all the data. GS conducted statistical analyses. All authors assisted in the final manuscript and agreed to its final approval before submission. IK is responsible for the overall content as guarantor. IK accepts full responsibility for the finished work and the conduct of the study, had access to the data, and controlled the decision to publish.
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests: This study had no competing financial interests. Interests disclosed in the international Committee of Medical Journal Editors (ICMJE) conflict of interest forms are as follows: IKH has received consulting fees from Novartis and GSK and is a member of the OARSI executive committee. MK has received grants from IMI APPROACH and the Dutch Arthritis Society, royalties/licences from Wolters Kluwer and Springer Verlag, and consulting fees from AbbVie, Pfizer, Kiniksa Flexion, Galapagos, CHDR, Novartis and UCB, and she is a member of the OARSI board, the EULAR council and President of the Dutch Society for Rheumatology.
Provenance and peer review: Not commissioned; externally peer reviewed.
Supplemental material: This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
Data availability statement
Data are available upon reasonable request. The data generated from this study will not be uploaded to a public repository, but can be made available from the corresponding authors to researchers on reasonable request, subject to a data sharing agreement.
Ethics statements
Patient consent for publication:
Not applicable.
Ethics approval:
Not applicable.
Acknowledgements
We thank the librarian Elise Davis-Keaveny, Diakonhjemmet Hospital, for supporting the literature searches.
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