Treatment response in rheumatoid arthritis is predicted by the microbiome: a large observational study in UK DMARD-naïve patients.

OBJECTIVES: Disease-modifying antirheumatic drugs (DMARDs) are first line treatment in rheumatoid arthritis (RA). Treatment response to DMARDs is patient-specific, dose efficacy is difficult to predict and long-term results variable. The gut microbiota are known to play a pivotal role in prodromal and early-disease RA, manifested by Prevotella spp. enrichment. The clinical response to therapy may be mediated by microbiota, and large-scale studies assessing the microbiome are few. This study assessed whether microbiome signals were associated with, and predictive of, patient response to DMARD-treatment. Accurate early identification of those who will respond poorly to DMARD therapy would allow selection of alternative treatment (e.g. biologic therapy), and potentially improve patient outcome. METHODS: A multicentre, longitudinal, observational study of stool- and saliva microbiome was performed in DMARD-naïve, newly diagnosed RA patients during introduction of DMARD treatment. Clinical data and samples were collected at baseline (n = 144) in DMARD-naïve patients and at six weeks (n = 117) and 12 weeks (n = 95) into DMARD-therapy. Samples collected (n = 365 stool, n = 365 saliva) underwent shotgun sequencing. Disease activity measures were collected at each timepoint and minimal clinically important improvement determined. RESULTS: In total, 26 stool microbes were found to decrease in those manifesting a minimal clinically important improvement. Prevotella spp. and Streptococcus spp. were the predominant taxa to decline following six weeks and 12 weeks of DMARDs, respectively. Furthermore, baseline microbiota of DMARD-naïve patients were indicative of future response. CONCLUSION: DMARDs appear to restore a perturbed microbiome to a eubiotic state. Moreover, microbiome status can be used to predict likelihood of patient response to DMARD.

Clinically important improvement thresholds for Harris Hip Score and its ability to predict revision risk after primary total hip arthroplasty.

BACKGROUND: Some aspects of validity are missing for the Harris Hip Score (HHS). Our objective was to examine the clinically meaningful change thresholds, responsiveness and the predictive ability of the HHS questionnaire. METHODS: We included a cohort of patients who underwent primary total hip arthroplasty (THA) and responded to the HHS preoperatively and at 2- or 5-year post-THA (change score) to examine the clinically meaningful change thresholds (Minimal clinically important improvement, MCII; and moderate improvement), responsiveness (effect size (ES) and standardized response mean (SRM)) based on pre- to post-operative change and the predictive ability of change score or absolute postoperative score at 2- and 5-years post-THA for future revision. RESULTS: Two thousand six hundred sixty-seven patients with a mean age of 64 years completed baseline HHS; 1036 completed both baseline and 2-year HHS and 669 both baseline and 5-year HHS. MCII and moderate improvement thresholds ranged 15.9-18 points and 39.6-40.1 points, respectively. ES was 3.12 and 3.02 at 2- and 5-years; respective SRM was 2.73 and 2.52. There were 3195 hips with HHS scores at 2-years and 2699 hips with HHS scores at 5-years (regardless of the completion of baseline HHS; absolute postoperative scores). Compared to patients with absolute HHS scores of 81-100 (score range, 0-100), patients with scores <55 at 2- and 5-years had higher hazards (95 % confidence interval) of subsequent revision, 4.34 (2.14, 7.95; p < 0.001) and 3.08 (1.45, 5.84; p = 0.002), respectively. Compared to HHS score improvement of  >50 points from preoperative to 2-years post-THA, lack of improvement/worsening or 1-20 point improvement were associated with increased hazards of revision, 18.10 (1.41, 234.83; p = 0.02); and 6.21 (0.81, 60.73; p = 0.10), respectively. CONCLUSIONS: HHS is a valid measure of THA outcomes and is responsive to change. Both absolute HHS postoperative scores and HHS score change postoperatively are predictive of revision risk post-primary THA. We defined MCID and moderate improvement thresholds for HHS in this study.

Comparison of intra-articular hyaluronic acid injections with transcutaneous electric nerve stimulation for the management of knee osteoarthritis: a randomized controlled trial.

OBJECTIVE: To compare the effects of intra-articular hyaluronic acid (HA; ARTZ) and transcutaneous electric nerve stimulation (TENS) in the treatment of patients with knee osteoarthritis. DESIGN: A prospective, randomized controlled trial. SETTING: Rehabilitation clinic of a teaching hospital. PARTICIPANTS: Patients with knee osteoarthritis (N=50; aged 51-80y) were randomly assigned to the HA group (n=27) or the TENS group (n=23). INTERVENTIONS: The HA group received intra-articular HA injection into the affected knee once a week for 5 consecutive weeks, and the TENS group received a 20- minute session of TENS 3 times a week for 4 consecutive weeks. MAIN OUTCOME MEASURES: The primary outcome measures used were the visual analog scale (VAS) for pain and the Lequesne index. The secondary outcome measures were range of motion of the knee, walking time, pain threshold, patient global assessment, and disability in activities of daily living. All subjects were assessed at baseline, and at 2 weeks, 2 months, and 3 months after the treatments were completed. RESULTS: The TENS group exhibited a significantly greater improvement in VAS than the HA group at 2 weeks' follow-up (4.17 ± 1.98 vs 5.31 ± 1.78, respectively; P=.03). In addition, the TENS group also exhibited a significantly greater improvement in the Lequesne index than the HA group at 2 weeks' follow-up (7.78 ± 2.08 vs 9.85 ± 3.54, respectively; P=.01) and at 3 months' follow-up (7.07 ± 2.85 vs 9.24 ± 4.04, respectively; P=.03). CONCLUSIONS: TENS with silver spike point electrodes was observed to be more effective than intra-articular HA injection for patients with knee osteoarthritis in improving the VAS for pain at 2 weeks' follow-up as well as the Lequesne index at 2 weeks' and 3 months' follow-up.

Association between disease-specific quality of life and magnetic resonance imaging outcomes in a clinical trial of prolotherapy for knee osteoarthritis.

OBJECTIVE: To assess the relation between knee osteoarthritis (KOA)-specific quality of life (QOL) and intra-articular cartilage volume (CV) in participants treated with prolotherapy. KOA is characterized by CV loss and multifactorial pain. Prolotherapy is an injection therapy reported to improve KOA-related QOL to a greater extent than blinded saline injections and at-home exercise, but its mechanism of action is unclear. DESIGN: Two-arm (prolotherapy, control), partially blinded, controlled trial. SETTING: Outpatient. PARTICIPANTS: Adults with ≥3 months of symptomatic KOA (N=37). INTERVENTIONS: Prolotherapy: 5 monthly injection sessions; CONTROL: blinded saline injections or at-home exercise. MAIN OUTCOME MEASURES: Primary: KOA-specific QOL scores (baseline, 5, 9, 12, 26, and 52wk; Western Ontario and McMaster University Osteoarthritis Index). Secondary: KOA-specific pain, stiffness, function (Western Ontario McMaster University Osteoarthritis Index subscales), and magnetic resonance imaging-assessed CV (baseline, 52wk). RESULTS: Knee-specific QOL improvement among prolotherapy participants exceeded that among controls (17.6±3.2 points vs 8.6±5.0 points; P=.05) at 52 weeks. Both groups lost CV over time (P<.05); no between-group differences were noted (P=.98). While prolotherapy participants lost CV at varying rates, those who lost the least CV ("stable CV") had the greatest improvement in pain scores. Among prolotherapy participants, but not control participants, the change in CV and the change in pain (but not stiffness or function) scores were correlated; each 1% CV loss was associated with 2.7% less improvement in pain score (P<.05). CONCLUSIONS: Prolotherapy resulted in safe, substantial improvement in KOA-specific QOL compared with control over 52 weeks. Among prolotherapy participants, but not controls, magnetic resonance imaging-assessed CV change (CV stability) predicted pain severity score change, suggesting that prolotherapy may have a pain-specific disease-modifying effect. Further research is warranted.

Clinicoradiological Risk Factors Associated with Inability to Achieve Minimum Clinically Important Difference in Operated Cases of Cervical Spondylotic Myelopathy.

STUDY DESIGN: This is a retrospective cohort study. PURPOSE: This study aimed to identify the clinicoradiological risk factors associated with the inability to achieve minimum clinically important difference (MCID) on the modified Japanese Orthopaedic Association (mJOA) Scale in operated cases of cervical spondylotic myelopathy (CSM). OVERVIEW OF LITERATURE: Only a few studies have evaluated the outcomes of surgery performed for CSM using MCID on the mJOA scale. METHODS: We analyzed 124 operated CSM cases from March 2019 to April 2021 for preoperative clinical features, cervical sagittal radiographic parameters, and magnetic resonance imaging (MRI) signal intensities (SI). The risk factors associated with missing the MCID (poor outcome) on mJOA at the final follow-up were identified using binary logistic regression. Multivariate analysis was used to find significant risk factors, and odds ratios (OR) were computed. RESULTS: A total of 110 men (89.2%) and 14 women (10.8%) with an average age of 53.5±13.2 years were included in the analysis. During the last follow-up, 89 cases (72.1%) achieved MCID (meaningful gains following surgery) while 35 (27.9%) could not. The final model identified the following parameters as significant risk factors for poor outcome: increased duration of symptoms (OR, 6.77; p=0.001), lower preoperative mJOA scale (OR, 0.75; p=0.029), the presence of multilevel T2-weighted (T2W) MRI SI (OR, 4.79; p=0.004), and larger change in cervical sagittal vertical axis (ΔcSVA) (OR, 1.06; p=0.013). Also, an increase in cSVA postoperatively correlated with a reduced functional recovery rate (r=-0.4, p<0.001). CONCLUSIONS: Surgery for CSM leads to significant functional benefits. However, poorer outcomes are observed in cases of greater duration of symptoms, higher preoperative severity with multilevel T2W MRI SI, and a larger increase in the postoperative cSVA (sagittal imbalance).

Minimal clinically important improvement response in patients with severe osteoarthritis of the knee: Short report from a survey of clinicians.

The minimal clinically important improvement (MCII) is the smallest change that signifies an important improvement. Disease severity may complicate MCII. We developed an eight-question survey examining MCII in patients with severe knee osteoarthritis (Kellgren-Lawrence grade 4). Twenty-seven of 101 clinicians completed the survey. An MCII of 20% was selected most frequently for pain, function, and patient global assessment. Clinicians were divided on responder rate, selecting 20%, 30%, and 50% equally. These findings suggest a 20% MCII may be useful in patients with severe osteoarthritis, but that there is not enough evidence to support a responder rate in this population.