osteoarthritis, knee

Importance: Physical therapy and glucocorticoid injections are initial treatment options for knee osteoarthritis, but available data indicate that most patients receive one or the other, suggesting they may be competing interventions. The initial cost difference for treatment can be substantial, with physical therapy often being more expensive at the outset, and cost-effectiveness analysis can aid patients and clinicians in making decisions.

Objective: To investigate the incremental cost-effectiveness between physical therapy and intra-articular glucocorticoid injection as initial treatment strategies for knee osteoarthritis.

Design, setting, and participants: This economic evaluation is a secondary analysis of a randomized clinical trial performed from October 1, 2012, to May 4, 2017. Health economists were blinded to study outcomes and treatment allocation. A randomized sample of patients seen in primary care and physical therapy clinics with a radiographically confirmed diagnosis of knee osteoarthritis were evaluated from the clinical trial with 96.2% follow-up at 1 year.

Interventions: Physical therapy or glucocorticoid injection.

Main outcomes and measures: The main outcome was incremental cost-effectiveness between 2 alternative treatments. Acceptability curves of bootstrapped incremental cost-effectiveness ratios (ICERs) were used to identify the proportion of ICERs under the specific willingness-to-pay level ($50 000-$100 000). Health care system costs (total and knee related) and health-related quality-of-life based on quality-adjusted life-years (QALYs) were obtained.

Results: A total of 156 participants (mean [SD] age, 56.1 [8.7] years; 81 [51.9%] male) were randomized 1:1 and followed up for 1 year. Mean (SD) 1-year knee-related medical costs were $2113 ($4224) in the glucocorticoid injection group and $2131 ($1015) in the physical therapy group. The mean difference in QALY significantly favored physical therapy at 1 year (0.076; 95% CI, 0.02-0.126; P = .003). Physical therapy was the more cost-effective intervention, with an ICER of $8103 for knee-related medical costs, with a 99.2% probability that results fall below the willingness-to-pay threshold of $100 000.

Conclusions and relevance: A course of physical therapy was cost-effective compared with a course of glucocorticoid injections for patients with knee osteoarthritis. These results suggest that, although the initial cost of delivering physical therapy may be higher than an initial course of glucocorticoid injections, 1-year total knee-related costs are equivalent, and greater improvement in QALYs may justify the initial higher costs.

Objectives. We updated the evidence from our 2018 report assessing persistent improvement in outcomes following completion of therapy for noninvasive nonpharmacological treatment for selected chronic pain conditions.

Data sources. Electronic databases (Ovid MEDLINE®, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews) through November 2017 (for prior report) and from September 2017 through September 2019 (for this update report), reference lists, ClinicalTrials.gov, and our previous report.

Review methods. Using predefined criteria, we selected randomized controlled trials (RCTs) of noninvasive nonpharmacological treatments for five common chronic pain conditions (chronic low back pain; chronic neck pain; osteoarthritis of the knee, hip, or hand; fibromyalgia; and tension headache) that reported results for a at least 1 month postintervention. We analyzed effects and assessed strength of evidence (SOE) at short term (1 to <6 months following treatment completion), intermediate term (≥6 to <12 months), and long term (≥12 months).

Results. We included 233 RCTs (31 new to this update). Many were small (N<70), and evidence beyond 12 months after treatment completion was sparse. The most common comparison was with usual care. Evidence on harms was limited, with no evidence suggesting increased risk for serious treatment-related harms for any intervention. Effect sizes were generally small for function and pain.

Chronic low back pain: Psychological therapies were associated with small improvements compared with usual care or an attention control for both function and pain at short-term, intermediate-term, and long-term followup (SOE: moderate). Function improved over short and/or intermediate term for exercise, low-level laser therapy, spinal manipulation, massage, yoga, acupuncture, and multidisciplinary rehabilitation (SOE moderate at short term for exercise, massage, and yoga; low for all others). Improvements in pain at short term were seen for massage, mindfulness-based stress reduction, acupuncture, and multidisciplinary rehabilitation (SOE: moderate), and exercise, low-level laser therapy, and yoga (SOE: low). At intermediate term, spinal manipulation, yoga, multidisciplinary rehabilitation (SOE: moderate) and exercise and mindfulness-based stress reduction (SOE: low) were associated with improved pain. Compared with exercise, multidisciplinary rehabilitation improved both function and pain at short and intermediate terms (small effects, SOE: moderate.)

Chronic neck pain: In the short term, low-level laser therapy (SOE: moderate) and massage (SOE: low) improved function and pain. Exercise in general improved function long term, and combination exercise improved function and pain both short and long term compared with usual care (SOE: low). Acupuncture improved function short and intermediate term, but there was no pain improvement compared with sham acupuncture (SOE: low). Compared with acetaminophen, Pilates improved both function and pain (SOE: low).

Osteoarthritis pain: Exercise resulted in small improvements in function and pain at short-term (SOE: moderate) and long-term (SOE: low), and moderate improvement at intermediate-term (SOE: low) followup for knee osteoarthritis versus nonactive comparators. Small improvements in function and pain with exercise were seen for hip osteoarthritis short term (SOE: low). Functional improvement persisted into intermediate term, but pain improvement did not (SOE: low).

Fibromyalgia: Functional improvements were seen with exercise, mind-body practices, multidisciplinary rehabilitation (SOE: low) and acupuncture (SOE: moderate) short term compared with usual care, attention control, or sham treatment. At intermediate term, there was functional improvement with exercise and acupuncture (SOE: moderate), cognitive-behavioral therapy (CBT), mindfulness-based stress reduction, myofascial release, and multidisciplinary rehabilitation (SOE: low). Long term, functional improvements persisted for multidisciplinary rehabilitation without improvement in pain (SOE: low). Compared with exercise, tai chi conferred improvement in function short and intermediate term (SOE: low). Pain was improved with exercise (short and intermediate term, SOE moderate), and for CBT (short term), mindfulness practices, and multidisciplinary rehabilitation (intermediate term) (SOE low).

Chronic tension headache: Evidence was sparse and the majority of trials were of poor quality. Spinal manipulation resulted in moderate improvement in pain short term.

Conclusions. Trials identified subsequent to the earlier report largely support previous findings—namely that exercise, multidisciplinary rehabilitation, acupuncture, CBT, mindfulness practices, massage, and mind-body practices most consistently improve function and/or pain beyond the course of therapy for specific chronic pain conditions. Additional research, including comparisons with pharmacological and other active controls, on effects beyond the immediate post-treatment period is needed, particularly for conditions other than low back pain.

IMPORTANCE:

Even though osteoarthritis is a chronic and progressive disease, pharmacological agents are mainly studied over short-term periods, resulting in unclear recommendations for long-term disease management.

OBJECTIVE:

To search, review, and analyze long-term (≥12 months) outcomes (symptoms, joint structure) from randomized clinical trials (RCTs) of medications for knee osteoarthritis.

DATA SOURCES AND STUDY SELECTION:

The databases of MEDLINE, Scopus, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials were searched until June 30, 2018 (MEDLINE alerts through August 31, 2018) for RCTs of patients with knee osteoarthritis that had treatment and follow-up lasting 1 year or longer.

DATA EXTRACTION AND SYNTHESIS:

Data at baseline and at the longest available treatment and follow-up of 12 months' duration or longer (or the change from baseline) were extracted. A Bayesian random-effects network meta-analysis was performed.

MAIN OUTCOMES AND MEASURES:

The primary outcome was the mean change from baseline in knee pain. Secondary outcomes were physical function and joint structure (the latter was measured radiologically as joint space narrowing). Standardized mean differences (SMDs) and mean differences with 95% credibility intervals (95% CrIs) were calculated. Findings were interpreted as associations when the 95% CrIs excluded the null value.

RESULTS:

Forty-seven RCTs (22 037 patients; mean age range, mostly 55-70 years; and a higher mean proportion of women than men, around 70%) included the following medication categories: analgesics; antioxidants; bone-acting agents such as bisphosphonates and strontium ranelate; nonsteroidal anti-inflammatory drugs; intra-articular injection medications such as hyaluronic acid and corticosteroids; symptomatic slow-acting drugs in osteoarthritis such as glucosamine and chondroitin sulfate; and putative disease-modifying agents such as cindunistat and sprifermin. Thirty-one interventions were studied for pain, 13 for physical function, and 16 for joint structure. Trial duration ranged from 1 to 4 years. Associations with decreases in pain were found for the nonsteroidal anti-inflammatory drug celecoxib (SMD, -0.18 [95% CrI, -0.35 to -0.01]) and the symptomatic slow-acting drug in osteoarthritis glucosamine sulfate (SMD, -0.29 [95% CrI, -0.49 to -0.09]), but there was large uncertainty for all estimates vs placebo. The association with pain improvement remained significant only for glucosamine sulfate when data were analyzed using the mean difference on a scale from 0 to 100 and when trials at high risk of bias were excluded. Associations with improvement in joint space narrowing were found for glucosamine sulfate (SMD, -0.42 [95% CrI, -0.65 to -0.19]), chondroitin sulfate (SMD, -0.20 [95% CrI, -0.31 to -0.07]), and strontium ranelate (SMD, -0.20 [95% CrI, -0.36 to -0.05]).

CONCLUSIONS AND RELEVANCE:

In this systematic review and network meta-analysis of studies of patients with knee osteoarthritis and at least 12 months of follow-up, there was uncertainty around the estimates of effect size for change in pain for all comparisons with placebo. Larger RCTs are needed to resolve the uncertainty around efficacy of medications for knee osteoarthritis.