Description of Included Studies
Database searching initially identified 2157 records, of which 24 qualified for full review, and 13 studies were finally included (see Fig. 1) [18–31]. We additionally identified 42 studies in clinical trial registries, of which two were eligible for inclusion. However, both trials were finally excluded as, upon request for more information from the authors, one trial appeared to be terminated prematurely due to adverse events in the intervention group, and the other trial was completed but results were not published because the pharmaceutical company did not pursue the indication. No additional records were found through other sources. All disagreements between the authors (FK, RR) on article selection (n = 6) were resolved in a consensus meeting.
A total of 13 studies involving 864 participants (range 20–200, median 60), published between 2004 and 2014 were included. The mean age of participants was 62.8 years (reported in 12 trials). Four studies only included women, and in the other nine studies 84.5 % of the participants were women. Most studies (n = 11) only included participants with carpometacarpal (CMC) OA, and two trials only included participants with IP OA [20, 30], of which one study specifically included participants with erosive OA . In many studies (n = 11), radiographic evidence of OA had to be present on top of clinical signs and symptoms.
Four trials compared corticosteroids with placebo; three trials compared hyaluronic acid with placebo; six studies compared corticosteroids with hyaluronic acid; and single studies compared infliximab with placebo, corticosteroids with dextrose, different frequencies of hyaluronic acid injections and hyaluronic acid with a low versus a high molecular weight (Table 1). A total of 280 participants were treated with intra-articular corticosteroid injections: three trials used triamcinolone acetonide (dose range 10–40 mg in 0.5–1 ml, injected once in all studies) [18, 21, 24], two studies used triamcinolone hexacetonide (dose range 4–6 mg in 0.2–0.3 ml, injected once in both studies) [26, 30], two studies used betamethasone (3 mg in 0.5 ml injected three times in one trial, and a single injection of an unknown dose in 1 ml in the other) [22, 27], and two studies used methylprednisolone (40 mg in 0.5–1 ml injected once in both studies) [23, 31]. Two trials added a small dose of lidocaine 2 % to the injection fluid [23, 30]. A total of 360 participants were treated with intra-articular hyaluronate injections: three studies used Hylan G-F 20 (8 mg in 1 ml, injected once or twice) [19, 22, 24], six studies used sodium hyaluronate (dose range 5–15 mg in 0.5–1 ml, injected one to three times) [18, 21, 25, 27–29, 31]. A total of 172 participants were treated with placebo, comprising a saline injection of 0.2–1 ml in four studies [19, 20, 22, 26] or a local anaesthetic in two studies (0.1 ml lidocaine 2 % or 0.5 ml bupivacaine 0.5 %) [24, 30]. Finally, 30 participants in one trial were treated with intra-articular dextrose 20 % injections (0.5 ml, combined with 0.5 ml lidocaine 2 %, injected three times monthly) , and ten participants were treated with intra-articular infliximab injections (0.2 ml, 0.1 mg/ml, injected 12 times monthly) .
Risk of Bias
Most trials were assessed as being at high or unclear risk of bias for multiple items (Fig. 2). In the overall assessment, only two studies were judged as having a low risk of bias [26, 30]. Four trials were at low risk of selection bias, as they described adequate sequence generation and allocation concealment; the risk of selection bias in the other trials was high (n = 3) or unclear (n = 6). One additional trial was at high risk of selection bias even though sequence generation and allocation concealment were performed using methods associated with a low risk of bias, since this study selectively included participants based on the probability of a positive treatment effect (judged as high risk of bias in the item ‘other bias’) . Participants were adequately blinded in five trials; however, in the remaining studies, participants were not blinded (n = 4) or it was unclear whether participants were blinded (n = 4), although most trials (n = 8) adequately blinded the outcome assessor(s). One trial had unexplained incomplete outcome data and was assessed as being at high risk of attrition bias. The risk of attrition bias remained unclear in seven trials, for example because the number of participants finishing the study was not described (n = 5). Many trials had a high risk of reporting bias (n = 5), e.g. as they did not report all assessed outcomes at all time points or only reported p values. Other potential sources of bias were identified in five trials and included inappropriate statistical analyses for the selected study design (n = 2) [19, 20], exclusion of participants after inclusion  or after treatment allocation , and selectively including patients based on probability of a positive treatment effect (n = 2) [20, 22].
Effects of Interventions
Most studies were clinically too heterogeneous to compare, did not provide data eligible for meta-analysis (e.g. data only presented in figures, or presentation of point estimates without a measure of variance), and/or the risk of bias was judged to be too high to produce reliable results. Only results of two studies, comparing corticosteroid injections versus placebo in participants with CMC OA, could be pooled [24, 26]. The remaining studies are discussed narratively under each relevant comparison. A summary of the most important findings is presented in Table 2.
Intra-Articular Corticosteroids Versus Placebo
Three studies (n = 206) compared a corticosteroid injection with placebo in participants with CMC OA [22, 24, 26]. Pooled results from two studies (n = 166, unclear and low risk of bias) for our primary outcome measure pain on VAS showed no difference up to 26 weeks between intra-articular corticosteroids and placebo [MD −3.56 (95 % CI −13.87 to 6.75) on a 100-mm VAS; Fig. 3]. The third study (n = 40, unclear risk of bias) concluded that both groups showed a decrease in pain compared with baseline, although there were no significant between-group differences at any of the time points up to 26 weeks (data only presented graphically). Also, for the other reported efficacy outcomes [i.e. function (two trials), grip strength (one trial), pinch strength (one trial), pain on joint palpation (one trial), joint stiffness (one trial), patient global assessment (one trial), physician global assessment (one trial) and range of motion (one trial)], no between-group differences up to 26 weeks were found by any study in this comparison. No adverse events were observed in any of the treatment groups in two trials, although one trial  observed adverse events in both treatment groups [9/65 in the corticosteroid group (all local adverse events such as pain, swelling and skin or nail abnormalities) and 3/61 in the placebo group (of which two were local adverse events and one was a surgery unrelated to study medication)].
Spolidoro et al.  (n = 60, low risk of bias) studied participants with IP OA and found a decrease in pain compared with baseline for both groups, although there were no between-group differences for pain at rest at any of the time points up to 12 weeks. However, pain during joint movement improved more in the corticosteroid group than in those receiving placebo after 12 weeks [mean (SD) score on a 10-cm VAS after 12 weeks of 2.2 (2.9) vs. 4.0 (3.2), respectively]. Also, a significant decrease in joint swelling was found in the corticosteroid-treated group compared with the placebo group [1.1 (1.2) vs. 2.0 (1.3), respectively on a 10-cm VAS]. For the other reported efficacy outcomes (i.e. function [measured with both the Cochin questionnaire and the Australian/Canadian hand osteoarthritis index (AUSCAN)], grip strength, pinch strength and goniometry), no between-group differences were identified. The authors reported that no severe adverse events were observed in either treatment group.
Intra-Articular Hyaluronic Acid Versus Placebo
Three studies (n = 196) investigated an injection with hyaluronic acid compared with placebo in participants with CMC OA [19, 22, 24]. One trial investigated the same participants in both treatment groups by including one CMC joint in the intervention group and the contralateral joint in the placebo group . All studies [risk of bias: high (n = 1) and unclear (n = 2)] showed a decrease in pain compared with baseline in both groups, but no significant between-group differences were found up to 26 weeks in two studies, while one study did not formally investigate between-group differences. Furthermore, no between-group differences were reported for the other efficacy outcomes [i.e. function (three trials), grip strength (one trial), pinch strength (two trials) and range of motion of the thumb (one trial)]. No adverse events were observed in any of the treatment groups in two trials, although one trial  observed adverse events in both treatment groups [5/62 in the hyaluronic acid-group (three local adverse events and two cases of surgery unrelated to study medication) and 3/61 in the placebo group (two local adverse events and one case of surgery unrelated to study medication)].
Intra-Articular Corticosteroids Versus Hyaluronic Acid
Six studies (n = 405) investigated a corticosteroid injection compared with hyaluronic acid in participants with CMC OA [18, 21, 22, 24, 27, 31]. For the primary outcome—pain on VAS—all trials showed an improvement in both treatment groups. Four trials [risk of bias: high (n = 2) and unclear (n = 2)] showed no between-group difference in pain on VAS up to 26 weeks [22, 24, 27, 31], one trial (high risk of bias) described a transitory superior effect of corticosteroids at 1 and 6 months , and one trial (high risk of bias) concluded that the corticosteroid group initially displayed a better and faster pain relief up to 3 weeks but that hyaluronic acid was ‘non-inferior’ to corticosteroids thereafter . Three studies [risk of bias: high (n = 1) and unclear (n = 2)] reported no between-group differences in self-reported function after 26 weeks [22, 24, 27], although one trial (high risk of bias) reported temporarily more improvement in function in the corticosteroid group at 12 months of follow-up . Three of four trials assessing self-reported function reported an improvement in function in both intervention groups [18, 22, 27]. No between-group differences were found for most other reported efficacy parameters [i.e. grip strength (one trial), pinch strength (one trial), range of motion of the thumb (one trial), joint pain on pressure (one trial), quality of life (one trial) and joint crepitation (one trial)]. However, single studies reported temporarily more improvement in grip strength in the corticosteroid group at 1 month of follow-up , and transitory better relief of joint swelling in the corticosteroid group . In contrast, single studies also reported (transitory) beneficial effects in favour of hyaluronic acid injections in the outcomes pinch strength (temporarily more improvement after 12 weeks  and 24 weeks ), range of motion of the thumb (overall more improvement in the hyaluronic acid group ) and joint warmth (overall better relief of warmth in the hyaluronic acid group ). One trial only reported effects within each treatment group without formally comparing the two interventions for the outcomes function performance, grip strength and pinch strength .
Three trials reported adverse events in both treatment groups, although numbers were relatively low and equal in both groups [corticosteroid vs. hyaluronic acid groups: 4/28 vs. 4/28 (Fuchs et al. , not related to study medication), 5/40 vs. 5/48 (Monfort et al. , minor side effects, including pain and local swelling following the injection), 9/65 vs. 5/62 (Mandl et al. , local side effects such as pain, swelling and skin and nail abnormalities, and few cases of surgery unrelated to study medication)], although no adverse events were observed in any of the treatment groups in the remaining three studies in this comparison.
One study (n = 20, high risk of bias) investigated intra-articular infliximab injections compared with placebo in a non-randomised pilot study in participants with erosive IP OA . From each participant, the hand with the most severely affected finger joints was assigned to the intervention group; the other hand served as a control. Pain on VAS had significantly improved in the infliximab group after 12 months compared with baseline [mean (SD) 32.5 (15.1) vs. 75.3 (10.2), respectively, on a 100-mm VAS] and not in the placebo group [62.5 (20.4) vs. 50.5 (13.0)]. A formal between-group comparison was not possible due to the (known) baseline differences between the intervention and placebo groups. Pain on pressure also improved only in the infliximab group, although no differences between groups were found for the other reported efficacy outcomes (i.e. grip strength, morning stiffness and radiological score). No side effects, either local or systemic, were observed during the study.
One study (n = 60, unclear risk of bias) investigated intra-articular dextrose injections compared with corticosteroid injections in participants with CMC OA . Pain during movement on VAS improved in both groups, with better pain relief 24 weeks after the last injection in the dextrose group compared with the corticosteroid group [mean (SD) score on a 10-cm VAS after 24 weeks of 1.2 (1.6) vs. 2.4 (1.8), respectively]. The outcomes function and joint pain on pressure also improved more in the dextrose group than in the corticosteroid group [function after 24 weeks: 1.6 (1.3) vs. 2.6 (1.5) on the Health Assessment Questionnaire Disability Index (scale 0–9, higher is worse); results for pain on pressure were only presented graphically]. No between-group differences were found for pinch strength. Three participants experienced minor adverse events (increase in joint pain, which subsided in several days), although which treatment these participants had received is unclear.
Two studies compared different frequencies or different forms of hyaluronic acid with each other in participants with CMC OA. The first study (n = 42, high risk of bias) compared a single injection of hyaluronic acid with either 2- or 3-weekly injections [28, 29]. Pain on VAS improved only in both groups with multiple injections and not in the group with a single injection, although no between-group differences were found after 12 weeks [mean (SD) score on a 100-mm VAS after 12 weeks of 43.1 (22.8) vs. 39.5 (28.6) vs. 29.8 (21.9), respectively, for one, two or three injections]. Minor adverse events were observed in 30 % of participants in all treatment groups, involving local pain, swelling, heat and/or redness, which subsided within several hours to days. The second study (n = 80, unclear risk of bias) compared hyaluronic acid with a low molecular weight with that with a high molecular weight . Pain on VAS improved in both treatment groups, although no between-group differences were found after 12 weeks [mean (SD) score on a 10-cm VAS after 12 weeks of 4.23 (2.90) vs. 4.03 (2.56), respectively, for the low versus high molecular weight fluid]. Minor side effects were observed in both groups, including mild pain and/or ecchymosis in the injection site (exact numbers per treatment group not specified).