Triangular Titanium Implants for Minimally Invasive Sacroiliac Joint Fusion: 2-Year Follow-Up from a Prospective Multicenter Trial

Discussion

Our study, the first prospective multicenter report of 2-year outcomes after minimally invasive SI joint fusion, provides strong evidence that patients can be diagnosed with SI joint dysfunction and successfully treated with triangular titanium implants placed during a minimally invasive surgical procedure. Study data show marked improvement in SI joint pain extending to 2 years, with parallel changes in disability as measured by ODI, and quality of life as measured by two commonly used instruments (SF-36 and EQ-5D). The proportion of subjects with clinically important (≥15 points) improvement in ODI was meaningful (about two-thirds). Quality of life improvements were substantial as measured by EQ-5D and approximately 1 SD for SF-36. We observed parallel improvements in self-rated global assessments of pain levels, limitations in activities of daily living, and high rates of satisfaction and desirability of undergoing the procedure again. Full ambulatory status was preserved in the majority of patients. The proportion of subjects not working due to back pain decreased.

Results from our study are supported by several retrospective case series,^24–30 including some with up to 4.5- and 5-year follow-up,⁴⁹ as well as 12-month results from a prospective randomized trial that showed little response to non-surgical treatment in the same patient population.⁵⁰ As such, our trial provides strong support for minimally invasive SI joint fusion as a standard treatment choice in patients with SI joint dysfunction unresponsive to non-surgical treatment. Our study also confirms that a minimally invasive surgical approach is associated with expected benefits of minimal blood loss, relatively short procedure times, a short hospital length of stay, and a low rate of adverse events.

SI joint pain has a marked impact on quality of life. Baseline quality of life scores in study subjects are consistent with a high burden of disease⁵ and quality scores in our cohort were at least as depressed as those of other major orthopedic conditions commonly treated surgically, such as lumbar spinal stenosis and degenerative hip arthritis.⁵ We observed marked improvements in quality of life after SI joint fusion with two commonly used quality of life instruments (EQ-5D and SF-36). The improvements seen in all measured parameters (pain, disability and quality of life) were impressive given the long duration of SI joint pain (on average 5 years) and the high rate of failure of prior therapies (64% had received physical therapy, 94% had received SI joint steroid injections and 16% had received RF ablation). In contrast to other studies of spine surgeries, in which patients with prior spine surgery are typically excluded, our study allowed patients with prior lumbar fusion to participate, as this is known to be a risk factor for SI joint degeneration,⁵¹ possibly by increasing adjacent segment stresses.⁵² Prior lumbar fusion was common (44.2%) and many patients had a history of concomitant spine and hip disease, making the observed improvement in pain and QOL all the more impressive. Interestingly, pre-specified subgroup analysis showed that subjects with a history of prior lumbar fusion responded similarly to those without such a history.

Outcomes observed in our trial were comparable to those of other accepted surgical spine treatments. In our study, 69.1% of subjects had 15 or more point improvement in ODI at 2 years, values similar to that observed after CHARITE artificial disc replacement (68%⁵³). In an early study of lumbar fusion using recombinant bone morphogenetic protein, 83% of subjects had a 15-point or more improvement in ODI at month 24.⁵⁴ In another randomized trial of lumbar fusion with recombinant bone morphogenetic protein, 71% had 15-point improvements.⁵⁵ Mean improvement in ODI in our cohort (24.5 points) was about the same as that observed in SPORT's lumbar degenerative spondylolisthesis study (24 points⁵⁶), slightly larger than that observed in SPORT's lumbar stenosis trial (20 points in the “as treated” analysis of the randomized and observational cohort⁵⁷), and smaller than that observed in SPORT's lumbar disc herniation study (37.6 points⁵⁸). Improvements in our cohort occurred despite the common finding of prior lumbar fusion (44.2%) and concomitant hip or spine disease (24.4% spinal stenosis, 14.0% hip problems, 9.3% prior sacral trauma), conditions that often result in exclusion from other clinical trials.

SI joint pain has often been called “controversial” and challenging to diagnose, especially because other conditions (e.g., lumbar disc disease, hip osteoarthritis) can mimic SI joint pain. Unfortunately, no imaging study finding currently available is pathognomonic of SI joint dysfunction. Similar to other painful conditions, there is no gold standard for the diagnosis of any pain generator, and the idea that SI joint dysfunction diagnosis is challenging may stem, in part, from this void. Nonetheless, the diagnostic algorithm used in our study, which includes a typical history of off-center buttocks or low back pain below L5 and a positive Fortin finger test,⁵⁹ positive findings on 3 or more physical examination provocative maneuvers that stress the SI joint and reproduce SI joint pain, and confirmatory diagnostic SI joint block, identified a patient population with a high response rate to definitive treatment, with high long-term positive response rates. The high response rate validates the diagnostic approach. The use of diagnostic blocks in other pain conditions is commonly performed, and confirmatory diagnostic SI joint block is recommended by multiple pain and anesthesia specialty societies.^33–37

Opioid use in the US has been termed an epidemic^{60, 61} and concern remains about rising rates of prescribed opioid use for pain treatment. Chronic opioid use after lumbar fusion is common, occurring in >50% of patients in one study.⁶² In this study, chronic opioid use was associated with less return to work, and chronic opioid use prior to lumbar fusion was associated with failed back syndrome, additional surgery, depression and extended work loss. In a community-based comparison of surgical vs. non-surgical treatments for chronic low back pain, the proportion of patients taking opioids at 1 year decreased in non-surgical but not surgical patients.⁶³ In a prospective case series, the proportion of spine surgery patients who were taking opioids preoperatively and at 1 year did not change.⁶⁴ In the SPORT studies, the likelihood of opioid use amongst patients taking opioids at baseline decreased, while the incidence of new opioid use amongst non-users at base-line was modest.⁶⁵ Surgical treatment in SPORT was associated with a lower incidence of opioid use compared to non-surgical treatment, but the non-randomized nature of treatment selection severely limits the comparison. Moreover, the overall proportion of SPORT participants taking any opioids at each study visit was not reported. In our study, the incidence of opioid use at baseline was high (76.2%), which may reflect the underlying severity and chronicity of disease, and the reduction in opioid use was important (55.0% at 24 months, a reduction of 28.2%). This reduction was consistent with results from a randomized trial of SI joint fusion, showing a reduction of opioid use at 6 months in the SI joint fusion group but an increase in the non-surgical group.⁵⁰ We note that pain and disability did not resolve completely in our cohort, and the use of opioids remained high. Potential explanations include: 1) the presence of comorbid conditions that require opioid use, 2) the long duration of SI joint pain (average of 5 years in our cohort), which could itself limit pain and disability improvement due to social or psychological factors, and 3) complications from prior surgeries, especially lumbar fusion, which may have been provided to patients on the basis of misdiagnosis of lower back pain as coming from the spine instead of the SI joint.

Imaging findings in our study, read by radiologists at an independent core laboratory, were instructive. The titanium implants used to perform SI joint fusion were designed for biological fixation in bone, and the study's primary imaging endpoint, the proportion of subjects showing bony apposition to at least 30% of the implant surface area on both the iliac and sacral sides of 2 or more implants, occurred in 97% of treated sides, validating the implant's design.

The presence of bone on the implants suggests good bony integration and permanent stabilization of the SI joint. The number of implants with radiolucencies suggestive of implant loosening were small. As noted above, 97% of patients showed adherence of bone to at least 2 implants on both the sacral and ilial sides. The significance of scattered radiolucencies on implants is therefore unclear. Lucencies were more apparent on X-ray; these were typically around the leading edge of the implants that were placed less than 1 cm deep into the target sacrum. While lucencies along the implant's length may suggest a risk for inadequate fixation, the clinical impact may be limited in the long term by fusion across the SI joint itself. To date, only 1 of 172 patients underwent implant revision as a result of symptomatic loosening that was apparent along a major portion of the implant. Implant breach into the sacral foramen or beyond the sacral cortical bone anteriorly or posteriorly were present in a small number of patients, most of whom were asymptomatic. No device failures or migration were seen. Adverse bone reaction was generally absent, with a small number of cases showing small cystic changes or scattered erosions. Bone remodeling, predominantly in the ilium, was seen in >80% of treated SI joints, suggesting a positive impact of stabilization on bone structure.

Bridging bone across the SI joint was seen in a minority (approximately 22%) of cases. Given that a five-year study using the same imaging technique (pelvic CT) showed bridging bone in most cases (87%),⁴⁹ it is apparent that the technique used in our study may require longer periods of time to produce radiographically visible full bony bridging across the joint. Whether alternative techniques aimed at accelerating bony fusion across the SI joint (e.g., intraoperative decortication) produce incremental patient benefits is unknown. What is clear is that both short- and long-term data from our study indicate excellent pain, disability and quality of life improvements with the current device and technique, providing strong evidence that placement of porous TPS-coated triangular titanium implants transarticularly across the SI joint through a lateral approach results in clinically important beneficial patient outcomes. Implants clearly blocked joint motion and produced positive clinical outcomes even without radiographically visible arthrodesis of the SI joint (at 1 year).

In our cohort, revision surgeries were required in a small number of cases. Early revisions were performed in 2 cases to address radicular symptoms related to implant malposition; radicular pain resolved rapidly in both subjects on repositioning of offending devices. In 4 cases, SI joint pain did not improve and CT scan showed poor implant placement with caudal implants not fully engaging the sacrum. Revision surgery in these cases, with placement of additional implants, resulted in improved symptoms. These findings highlight the importance of placing a sufficient number of devices across the SI joint. Multiple studies have demonstrated superior SI joint stability with two-screw constructs compared to a single screw for unstable pelvic fractures.^66–68 Moreover, biomechanical studies show that placement of 3 iFuse implants across a SI joint reduced motion in flexion-extension, lateral bending, and axial rotation, with larger reductions observed using a transarticular configuration when compared with an inline (posterior) configuration.⁶⁹ One subject had pain associated with radiolucencies around the implant. Finally, in one study subject, failure to improve may have been explained by competing pathology. Overall, the revision rate for minimally invasive SI joint fusion appears to be low (3.6% or less at 4 years)⁷⁰ compared to other lumbar spine surgical procedures.^{71, 72}

All negative changes in health were collected as adverse events in our study, which resulted in a high number of reported events. However, because the study protocol used an international clinical trial standard (ISO14155:2011), which defines an adverse event as any negative change in health, most adverse events were unrelated to the study device or procedure. Only 7 events were deemed related to the study implant, of which 3 were related to poor implant placement causing nerve irritation and one was related to a fall associated with inadequate implant placement. 26 events were deemed related to the study procedure; the events were not unexpected and all resolved.

Several devices are now commercially available in the US and other geographies to perform minimally invasive SI joint fusion. Some of these devices are placed across the articular SI joint using a lateral-to-medial approach, as done in our study. Other devices (none of which are currently cleared by US FDA) are placed into the dorsal ligamentous portion of the SI joint via a posterior approach. The dorsal/posterior approach typically involves removal of a portion of the dense dorsal ligaments and the interosseous ligament, which may acutely destabilize the joint.^{73, 74} As no implants are placed across the SI joint with the dorsal technique, the biomechanics of the dorsal technique will differ from the lateral technique. Thus, while it is unknown whether the results of our study are applicable to other lateral transfixing devices, it is highly unlikely that our results are applicable to devices placed through a dorsal approach.

Our study has several advantages. First, participants were carefully screened against predetermined eligibility criteria and results represent the prospective experience of multiple surgeons. Second, the trial was executed according to an international clinical trial standard (ISO14155:2011). Third, study data were collected on electronic case report forms at pre-determined postoperative time points and all data were rigorously monitored and source verified.

The study has two primary limitations: 1) lack of a concurrent control group undergoing non-surgical treatment and, 2) a 24-month follow-up rate that was not as high as desired. Regarding the control group, direct comparisons can be made to INSITE (NC-T01681004), a companion, randomized clinical trial run contemporaneously with the current study. In INSITE, patients enrolled using identical eligibility criteria were randomized to receive either SI joint fusion using the same device/procedure as used herein or non-surgical management, consisting of medication management, physical therapy, SI joint steroid injections and radiofrequency ablation of the SI joint. Baseline characteristics of SIFI and INSITE were very similar.⁵⁰ 12-month results from INSITE indicated a profound difference in response between surgical and non-surgical care, with superior outcomes for all effectiveness parameters measured. Moreover, pain and disability responses to SI joint fusion were very similar between the two studies. INSITE's non-surgical group's response validates that the positive health effects seen in the current study are robust and distinct from the natural course of disease. Marked improvement in pain, disability and quality of life in the absence of a definitive intervention would not be expected anyway, given the long mean pain duration (>5 years on average) and the lack of prior response to physical therapy and steroid injections, which were common in the treated patient population and which have very little support in the literature as being effective.

Second, 13.4% of subjects were lost to follow-up during the study or did not have 24-month visits. Pain and ODI scores in exiting subjects were higher than subjects who continued to participate; however, the impact of missing values on pain and ODI scores were analyzed and found to be minor, and do not effect overall study conclusions. Recently published 24-month follow-up rates in spine surgery randomized trials conducted under investigational device exemption have shown similar long-term participation rates (83%/80%,⁷⁵ 89%/82%,⁷⁶ 98%/94%,⁷⁷ 91%/90%,⁷⁸ 81/82%,⁷⁹) to that in our study (86.6%).

Combined with results from other studies, our study confirms that SI joint fusion with iFuse implants has proven to be safe and effective, and hence a reasonable surgical treatment option for patients with SI joint dysfunction not responsive to non-surgical care.