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Volume:4 Issue:10 Number:1 ISSN#:2563-559X
OE Original

Application of Synthetic Cartilage Implant for Hallux Rigidus: A Systematic Review

Authored By: Application of Synthetic Cartilage Implant for Hallux Rigidus: A Systematic Review

October 6, 2021

How to Cite

OrthoEvidence. Application of Synthetic Cartilage Implant for Hallux Rigidus: A Systematic Review. OE Original. 2021;4(10):1. Available from: https://myorthoevidence.com/Blog/Show/151

Highlights


- We examined evidence from randomized controlled trials (RCTs) and non-randomized studies of intervention (NRSIs) regarding the use of synthetic cartilage implants [also known as polyvinyl alcohol (PVA) hydrogel implants or Cartiva] in patients with hallux rigidus.


- Our systematic literature search identified 1 eligible RCT, 3 analyses using the same RCT patient cohort, and 4 NRSIs. The RCT was a non-inferiority trial, and 2 NRSIs compared SCI vs. arthrodesis, while 1 NRSI investigated SCI vs. cheilectomy and 1 cheilectomy and Moberg osteotomy with SCIs vs. without SCIs.


- Current available evidence was insufficient to ascertain the efficacy of SCIs, and therefore unable to either recommend for or against the use of SCIs. More studies with high methodological study designs, preferably RCTs, are warranted.


- Making clinical recommendations is a complex decision-making process involving the consideration of evidence certainty, the balance between benefits and harms, values and preferences, as well as resource uses. A recommendation can only be made after carefully considering all relevant issues and weighting all relevant options.






Judith Baumhauer MD MPH

Professor, Associate Chair of Orthopaedic Surgery

University of Rochester School of Medicine and Dentistry



Thank you to the OrthoEvidence team as they choose to examine the evidence surrounding the use of synthetic cartilage implant for advanced stage Hallux Rigidus.  This SCI has been available for use in the US since 2016.


The first point to make emphasizes that single cohort or level four evidence were not reviewed nor considered high enough quality to be included in this review. As is well known, with these lower evidence studies, there is tremendous variation in the indication for surgery and the surgical techniques performed.  These studies do not aid in assessing the clinical recommendations regarding the use of this implant.


Like the OE experts, the authors of this RCT paper value high level evidence. The only prospective randomized multi-centered clinical trial examining the safety and efficacy of a synthetic cartilage implant compared to first metatarsal phalangeal joint arthrodesis was the result of an FDA trial. The study cost well over $25 million dollars. The composite endpoint was a requirement of the FDA for the analysis of the data. Although a second RCT confirming this work would be helpful, it is highly unlikely.


As mentioned, this RCT only randomized  patients who were candidates for arthrodesis. If a patient had a less severe arthritis and a cheilectomy was an option, he/she was not a candidate for this RCT study. This is an entirely different patient population and bears no comparison with the more severe arthritis results included in this prospective, randomized study.


The risk of bias assessment for our study was considered low.  The inability to reach a clinical recommendation is based on the lack of additional higher level evidence.  With only 5 years of SCI availability in the US, it is not surprising that no recommendation for or against could be reached.  As we continue to provide quality care to our patients, we will continue to perform meaningful research to advance our surgical subspecialty.    



Among individuals aged 50 years and over in the United States (US), approximately 2.5% are suffering from hallux rigidus, a disease characterized by degenerative arthritis of the first metatarsophalangeal (MTP) joint and being one of the most common arthritic conditions in the foot (Ho et al., 2017).


Non-operative management, such as non-steroidal anti-inflammatory medication, physical therapy, and intra-articular injection, is considered as the first-line treatment for early-stage hallux rigidus (Franc¸a et al., 2020; Ho et al., 2017).


For mild hallux rigidus, cheilectomy, removing excess osteophytes which occur above the main joint of the big toe to prevent dorsal impingement, can be a treatment option (Ho et al., 2017). The Moberg osteotomy, comprising a dorsiflexion osteotomy of the proximal phalanx, could be added to a standard cheilectomy for the treatment of hallux rigidus (Ho et al., 2017).


For hallux rigidus at advanced stages, operative procedures such as arthrodesis and multiple joint-sparing procedures, can be adopted (Franc¸a et al., 2020; Ho et al., 2017). MTP arthroplasty, one of joint-sparing surgical treatments, aims to preserve the length and motion of the MTP joint, and therefore providing lasting pain relief and good functional outcomes (Franc¸a et al., 2020).


Various types of implants have been used for MTP arthroplasty, such as silicone implants, ceramic implants, metallic implants, and more recently, synthetic cartilage implants (SCIs) made from polyvinyl alcohol (PVA) (Baumhauer et al., 2016; Cracchiolo et al., 1992; Nagy et al., 2014; Raikin et al., 2007).


In this OE Original, we systematically reviewed the evidence with regard to the clinical outcomes and safety outcomes of using SCIs in patients with hallux rigidus.






Methods


We searched Ovid MEDLINE, Ovid EMBASE, Cochrane Controlled Register of Trials (CENTRAL), and OrthoEvidence from inception to September 7, 2021 with both indexed terms and free text terms regarding SCI and hallux rigidus. Reference lists and existing systematic reviews (i.e., Smyth et al., 2020; Stibolt et al., 2019) were searched to identify additional eligible studies.


Our original inclusion criteria focused on randomized controlled trials (RCTs) investigating the efficacy and safety of using PVA hydrogel implant for patients with hallux rigidus. However, during the pilot literature search, we found that relevant RCTs were very few. Moreover, the identified RCTs were all from the same patient cohort. As a result, we decided to further include non-randomized studies of interventions (NRSIs).


As the Cochrane Handbook points out, “Most Cochrane Reviews seek to identify highly trustworthy evidence (typically only randomized trials) and if none is found then the review can be published as an ‘empty review’. However, as Cochrane Reviews also seek to inform clinical and policy decisions, it can be necessary to draw on the ‘best available’ evidence rather than the ‘highest tier’ of evidence for questions that have a high priority” (Higgins et al., 2021). However, given that the potential biases in NRSIs are generally greater than those in RCTs, inclusion of NRSIs that can “inform the review question directly and without a critical risk of bias” is extremely important (Higgins et al., 2021). In terms of what NRSIs to be included, Cochrane emphasizes the importance of “specific features of study design [of NRSIs] (e.g. which parts of the study were prospectively designed) rather than ‘labels’ for study designs (such as case-control versus cohort)” (Higgins et al., 2021). Inclusion of NRSIs regardless of their study limitations might yield a misleading effect estimate which might be “more harmful to future patients than no estimate at all” (Higgins et al., 2021).


For the present systematic review, we decided that the intervention effect estimated by difference between groups (intervention vs. comparator) rather than change over time (within the same group of participants over time) is the minimum requirement for the feature of study design, given that we needed a comparator to be compared against in order to inform our readers the relative treatment effect and safety of SCIs. Therefore, we included such NRSIs only following the methodological guidance provided by the Cochrane Handbook (Higgins et al., 2021).


We adopted the Cochrane risk-of-bias tool and the GRADE approach to determine the risk of bias and the quality of evidence for included RCTs, respectively. For NRSIs, we employed the Newcastle-Ottawa Scale for cohort/case-control studies to assess their methodological quality. Two reviewers independently worked on the study screening and selection processes.




Results


1. Characteristics of included studies


In total, 226 records were retrieved, among which 1 RCTpatient cohort was analyzed by 4 published studies (Baumhauer et al., 2016; Baumhauer et al., 2017; Glazebrook et al., 2018; Goldberg et al., 2017) and 4 eligible NRSIs (Brandao et al., 2020a; Brandao et al., 2020b; Chrea et al., 2020; Joo et al., 2021) were included. The characteristics of the included studies were shown in Table 1.


Baumhauer et al. (2016) was the original RCT (a non-inferiority study), whereas Baumhauer et al. (2017), Glazebrook et al. (2018), and Goldberg et al. (2017) either conducted subgroup analyses or reported different outcomes based on the RCT patient cohort from Baumhauer et al. (2016). All 4 NRSIs were published in 2020 or 2021. The allocation of participants to SCI or comparator was determined by the actions of researchers which were not specified in all 4 studies [i.e., allocation occurred as the result of some decision applied by the researchers (Higgins et al., 2013)].



Table 1. Characteristics of included studies

Study ID

Study Design

Sample Size

Condition

Intervention

Comparator

Baumhauer et al. (2016)

Non-inferiority randomized controlled trial

197

Advanced-stage hallux rigidus (hallux rigidus grade II, III, or IV)*

Synthetic cartilage implant (Cartiva)

Arthrodesis

Baumhauer et al. (2017)

Same patient cohort in Baumhauer et al. (2016)

Glazebrook et al. (2018)

Same patient cohort in Baumhauer et al. (2016)

Goldberg et al. (2017)

 Same patient cohort in Baumhauer et al. (2016)

Brandao et al. (2020a)

Comparative study

72

Symptomatic hallux rigidus

Synthetic cartilage implant (Cartiva)

Arthrodesis

Brandao et al. (2020b)

Comparative study

78

Symptomatic hallux rigidus

Synthetic cartilage implant (Cartiva)

Cheilectomy

Chrea et al. (2020)

Comparative study

166

Advanced-stage hallux rigidus (hallux rigidus grade II, III, or IV)*

Cheilectomy and Moberg osteotomy with synthetic cartilage implant (Cartiva)

Cheilectomy and Moberg osteotomy without synthetic cartilage implant

Joo et al. (2021)

Comparative study

181

Advanced-stage hallux rigidus

Synthetic cartilage implant (Cartiva)

Arthrodesis

* Hallux rigidus grade was from Coughlin et al. (2003)




In terms of risk of bias, the only RCT done by Baumhauer et al. (2016) was not able to blind participants and investigators due to the nature of the intervention. The risk of bias in random sequence generation, allocation concealment, incomplete outcome data, selective reporting, and surgeons’ experience was low.


We used NOS for cohort studies to assess the methodological quality of NRSIs. The total NOS scores of the 4 NRSIs ranged from 3 to 5, indicating a high risk of bias (NOS highest score is 8).



2. Evidence synthesis


The RCT conducted by Baumhauer et al. (2016) was a non-inferiority trial, meaning that at best we could only draw a conclusion that SCI is not inferior to the comparator. With the RCT alone, we were unable to make conclusions about superiority. Moreover, the included NRSIs had serious risk of bias. As a result, we did not conduct quantitative evidence synthesis. Instead, we only conducted a narrative summary of the evidence.



2.1 SCI vs. Arthrodesis


The included RCTs compared SCI (or PVA hydrogel implant, or Cartiva) with arthrodesis, as did the NRSIs conducted by Brandao et al. (2020a) and Joo et al. (2021).



2.1.1 SCI vs. Arthrodesis -- RCT evidence


  • The RCT conducted by Baumhauer et al. (2016) was a multi-center non-inferiority trial. Patients (N = 197) with advanced hallux rigidus [Coughlin’s et al. (2003) hallux rigidus grade II, III, or IV) were randomized to the SCI group or the MTP joint arthrodesis group (2:1). Twenty-two additional patients also received SCI without being randomized.


The primary outcome, which was a composite outcome, consisted of 3 outcome measures, including a) the Foot and Ankle Ability Measure (FAAM) sports score at 12 months post treatment, b) pain on a visual analog scale at 12 months post treatment (VAS), and c) major adverse events, such as revisions, removals, reoperations and/or supplemental fixations, device displacement, device fragmentation, development of avascular necrosis, malunion, nonunion of arthrodesis, and/or hardware failures.


The authors evaluate each participant’s composite ending point and count it as a success if the within-group pre- and post-surgery change in FAAM sports score at 12 months remained insignificant, the within-group pre- and post-surgery improvement in VAS pain at 12 months was >= 30%, and no major adverse events. The authors calculated the proportion of participants who had a success composite ending point for each group, the difference in the proportions between the SCI group and the arthrodesis group, as well as 1-sided 95% confidence interval (CI) for the difference between the SCI group and the arthrodesis group. Non-inferiority was considered if the lower boundary of the CI was greater than the equivalence limit (> -15%).


Baumhauer et al. (2016) found that SCI was not inferior to arthrodesis for the treatment of hallux rigidus in terms of preserving function, reducing pain, and being safe.


  • Baumhauer et al. (2017), Goldberg et al. (2017), and Glazebrook et al. (2018) conducted analysis using the patient cohort from Baumhauer et al. (2016).


Baumhauer et al. (2017) conducted subgroup analyses and determined whether the severity of hallux rigidus played a role in the efficacy and safety outcomes in patients receiving SCI. About 29% (59/202), 55% (110/202), and 16% (33/202) of the participants were classified as hallux rigidus grades 2, 3, and 4 according Coughlin’s et al. (2003) standards, respectively (Baumhauer et al., 2017). The authors found no correlation between hallux rigidus severity and active peak dorsiflexion (–0.069, P = 0.327) or VAS pain (–0.078, P = 0 .271). The proportions of successes determined based on the composite ending point described in Baumhauer et al. (2016) were similar between the SCI group and the arthrodesis group, when stratifying participants by disease severity.


Goldberg et al. (2017) also investigated the possible associations between patient characteristics and the composite outcome described in Baumhauer et al. (2016). The study found no significant differences in the composite ending point between SCI and arthrodesis, when participants were stratified by patient characteristics such as the severity of hallux rigidus determined by Coughlin’s et al. (2003) standards, patient gender, age, body mass index (BMI), symptom duration, etc (Goldberg et al., 2017).


Glazebrook et al. (2018), using the same patient cohort from Baumhauer et al. (2016), retrospectively reviewed the RCT data and mainly found that the operative time in the SCI group was significantly less than the time in the arthrodesis group [mean: 35 minutes, standard deviation (SD): 12.3 vs. 58 (21.5), P < 0.001].



2.1.2 SCI vs. Arthrodesis -- evidence from NRSIs


  • Brandao et al. (2020a) selected patients at a single center with symptomatic hallux rigidus who underwent SCI hemiarthroplasty (N = 30) or arthrodesis (N = 42) and compared the sporting ability between the groups using the FAAM sports score. The study found no statistically significant difference in the FAAM sports scores between the SCI and arthrodesis group (Brandao et al., 2020a). Brandao et al. (2020a) also reported 1 revision at 17 months post-operative because of pain in the SCI group, whereas there were no revisions in the arthrodesis group.


  • Joo et al. (2021) compared outcomes on physical function and pain interference levels between patients receiving SCI (N = 59) and those undergoing arthrodesis (N = 122) using the Patient-Reported Outcomes Measurement Information System (PROMIS). Patients in the analysis were selected from a single, tertiary academic medical center. The study found no differences in the pain interference levels or adverse events between SCI and arthrodesis, but that the physical function t scores at most follow-up time points were superior in the SCI group than those in the arthrodesis group.


2.2 SCI vs. Cheilectomy


Brandao et al. (2020b) identified patients undergoing either SCI (N = 55) or cheilectomy (N = 23) from a single center. The study found that cheilectomy resulted in significant improvements in the Manchester Oxford Foot and Ankle Questionnaire (MOXPQ) index score as well as the MOXPQ walking/standing subscore and the social interaction subscore, compared to SCI (Brandao et al., 2020b). There was no significant difference in the MOXPQ pain score or the FAAM sports score between SCI and cheilectomy (Brandao et al., 2020b). No adverse events were reported for either group (Brandao et al., 2020b).



2.3 Cheilectomy and Moberg osteotomy with SCI vs. without SCI


Chrea et al. (2020) selected patients who underwent cheilectomy and Moberg osteotomy with

 (N = 72) or without (N = 94) an SCI from a single medical center. The authors found that both groups had significant within-group pre- and post-operation improvements in outcomes such as PROMIS physical function, pain interference, pain intensity, and global physical health (Chrea et al., 2020). However, when comparing outcomes between groups, cheilectomy and Moberg osteotomy without an SCI resulted in a significant improvement in PROMIS physical function and pain intensity, compared to cheilectomy and Moberg osteotomy with an SCI (Chrea et al., 2020). In addition, In the cheilectomy and Moberg osteotomy without an SCI group, there was 1 revision arthrodesis, while in the cheilectomy and Moberg osteotomy with an SCI group, there were 3 revisions, 1 reimplantation, 1 conversion to arthrodesis, and 1 revision to correct hyperdorsiflexion (Chrea et al., 2020). Considering all outcomes, Chrea et al. (2020) concluded that cheilectomy and Moberg osteotomy with an SCI might “provide equivalent or better relief … while avoiding potential risks associated with the implant [SCI]”.



Discussion


In this OE Original, we conducted a systematic review to examine current best available evidence with regard to the efficacy and safety of SCIs (also known as PVA hydrogel implant, or Cartiva) in patients with hallux rigidus.


Our systematic literature search results suggested that available RCT evidence was very limited. Only 1 RCT conducted by Baumhauer et al. (2016) was identified; 3 additional included studies conducted analyses using the patient cohort from the original RCT. To better serve the purpose of informing our readers, who are mostly clinicians, we also included relevant NRSIs in this systematic review. Four NRSIs each of which involved a comparison group were included.


After carefully examining the included studies, we decided not to conduct meta-analyses to avoid generating misleading effect estimates due to the following reasons: First, the only RCT adopted a non-inferiority design using a composite ending point (i.e., reduction in VAS pain, preserving function measured by FAAM sports score, and absence of major adverse events, see Section 2.1.1 for details). A meta-analysis of each individual outcome from the composite outcome might not be appropriate. Second, the risk of bias for all 4 NRSIs were also serious as determined by the Newcastle-Ottawa Scale tool.


In terms of SCI vs. arthrodesis, current limited evidence does not support the superiority of SCI. The only RCT (Baumhauer et al., 2016) indicated that SCI was non-inferior to arthrodesis, while the 2 relevant NRSIs (Brandao et al., 2020a; Joo et al., 2021) also found no differences in the majority of the main outcomes between SCI and arthrodesis. For comparisons of SCI vs. cheilectomy or Cheilectomy and Moberg osteotomy with SCI vs. without SCI, the comparators even outperformed SCI in some outcome measures. For instance, cheilectomy led to significant improvements in the MOXPQ index score, compared to SCI (Brandao et al., 2020b).


Our systematic review concluded that current evidence was insufficient to ascertain any conclusion. As a result, we were not able to either support or dispute the use of SCI in hallux rigidus from the perspective of efficacy. More studies with high methodological quality, preferably RCTs, were warranted.


Moreover, making clinical recommendations is a complex decision-making process which involves not only the consideration of evidence certainty but also the contemplation of the balance between benefits and harms, values and preferences, as well as resource uses. A recommendation can only be made after carefully considering all relevant issues and weighting all relevant options.




Bottom Line


Current evidence regarding the use of synthetic cartilage implants for patients with hallux rigidus was very limited. More studies with high methodological quality, preferably RCTs, were required.





Reference


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Baumhauer, J. F., et al. (2017). Correlation of Hallux Rigidus Grade With Motion, VAS Pain, Intraoperative Cartilage Loss, and Treatment Success for First MTP Joint Arthrodesis and Synthetic Cartilage Implant. Foot & ankle international, 38(11), 1175-1182. doi:https://dx.doi.org/10.1177/1071100717735289

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