Written by: Dr. Ronak Patel, Dr. Chad Hille, and Dr. Chandana Keshavamurthy from Ochsner Medical Center

Based on: Deyle et al. NEJM.2020;382(15):1420-29 (pubmed link)

Topic Overview

Knee osteoarthritis is a very common problem in the United States and also a leading cause of disability. Unlike in Rheumatoid arthritis, where disease modifying agents are the norm, we have no such luxury in the management of osteoarthritis. There are many clinical trials which have shown promising results for compounds that:

• Arrest structural progression, which include cathepsin inhibitors, Wnt inhibitors, anabolic growth factors.
• Reduce pain which include nerve growth factor inhibitors.

To-date no drugs are approved by the FDA. Managing the symptoms is the main stay. This includes pain management and therapies which focus on improving the quality of life. Data from varying population cohorts suggest that nearly 40 to 50% of the patients in the cohort receive intra articular steroid injections prior to total knee replacements. In our day to day practice we offer physical therapy for many of our patients, but not all of them consistently respond to the treatment offered, similarly we offer intra articular corticosteroid injections often with varying results.

We do know from various clinical trials of treatments for osteoarthritis that physical therapy offers short term and long term relief of symptoms, offers functional improvement, decreases the need for pain medications particularly opioids. There is however paucity of data to help decide to what extent and duration intra articular corticosteroid injections offer benefit. Not to mention, the complications from the intra articular corticosteroid injections, including but not limited to joint infections, accelerated degradation of articular cartilage, subchondral insufficiency fractures.

Despite the controversy behind using intra articular corticosteroid injections and the guideline recommendations for physical therapy and lifestyle modifications, we see that intra articular corticosteroid injections are overutilized and physical therapy is underutilized in clinical practice. There are previous trials that combine intra articular corticosteroid injection to physical therapy with no added benefit and yet these practices have become a part of the treatment paradigm in managing knee osteoarthritis.

Let’s Talk About the Randomized Controlled Trial

The trial was designed to compare physical therapy to intra articular corticosteroid injections in a primary care setting in the US military health system . This was not a placebo controlled trial. Patients who were active duty or retired service members of the military health system and their family members with good access to health care participated in the trial, hence noncompliance/significant drop out rates was not an issue here.

Patients were randomly assigned in a 1: 1 ratio to receive intra articular corticosteroid injection or to undergo physical therapy. The mean body mass index of the entire cohort was 31.5 /obesity which is always thought to be a risk factor for knee OA is definitely noted here.

All patients had to meet the criteria laid by the American College of rheumatology clinical classification criteria for osteoarthritis of the knee , they had to have radio graphic evidence of osteoarthritis on weight bearing views assessed by Kellgren Lawrence scale, grading system, grades 1-4.  This is an important highlight, since this gives an opportunity to review the benefits of the therapy intervention on varying severity of the knee osteoarthritis.

However it so happens that majority of patients in the intra articular corticosteroid injection arm had Kellgren Lawrence grade 2, while majority of patients in the physical therapy arm had grade 3 scores. Not many patients had grade 1 scoring and a very few of them in both arms had grade 4 scoring, and lot more patients in the physical therapy arm had grade 4 as compared to the patients in the corticosteroid arm. To summarize, patients in the physical therapy arm had severe radiographic knee osteoarthritis as opposed to the intra articular corticosteroid injection arm.

Patients had physical therapy interventions including instructions and images for exercises for common joint mobilizations, there were hands on, manual techniques offered by the physical therapist. Patients underwent up to 8 physical therapy treatment sessions over the initial four to six week period, and patients could ask for additional 1 to 3 sessions at four months and nine months intervals. Patients in this group attended a mean of 11.8 treatment visits (range being 4 to 22).  Patients could get up to three intra articular corticosteroid injections in the one year time period. Patients in this group received a mean of 2.6 injections, range being 1 to 4.

Also noted was an overlap in the treatment interventions. 9% patients in the physical therapy arm also received intra articular corticosteroid injections. 18% in the intra articular corticosteroid injection arm received physical therapy in addition. The majority of patients had symptoms for an average of 100 months.  Symptoms included new swelling, locking, giving way feeling. 60% patients in both arms had bilateral knee osteoarthritis.

Statistical analysis was performed with the use of intention to treat approach.

Very clear primary outcome measures were defined early on, the primary outcome being the total score on the Western Ontario and McMaster Universities osteoarthritis index also known as WOMAC at one year. WOMAC contains 24 items and is composed of 3 subscales of pain, physical function, stiffness. Scores range from zero to 240, higher scores indicate worse pain, function, stiffness.  The secondary outcomes were the time needed to complete the timed up and go test and the score on the global rating of change scale at one year. The trial was sufficiently powered to meet the primary and the secondary endpoints. 

Trial Results

156 patients with the mean age of 56 years were selected and each group had 78 patients with all well matched baseline characteristics including pain severity ,disability. The baseline WOMAC scores were also well matched.

At one year, the group that underwent physical therapy met the primary and secondary outcome measures more than the group that had the intra articular corticosteroid injections.  The mean (±SD) baseline WOMAC scores were 108.8±47.1 in the glucocorticoid injection group and 107.1±42.4 in the physical therapy group. At 1 year, the mean scores were 55.8±53.8 and 37.0±30.7, respectively (mean between-group difference, 18.8 points; 95% confidence interval, 5.0 to 32.6), a finding favoring physical therapy.

Other outcome measures worth noting include the following :

• 10% patients in the physical therapy arm and 25% patients in the intra articular corticosteroid injections arm had no improvement from baseline, meaning they could not meet the 12% improvement in the minimal clinically important difference in the WOMAC score at one year.
• The median score on the global rating of change scale in both arms was above the clinically meaningful threshold of perceived improvement. But lot more patients in the intra articular corticosteroid injections arm than in the physical therapy arm did not report any perceived improvement on this scale.
• 14% of patients in the physical therapy arm and 33% of patients in the intra articular corticosteroid injections arm did not have a score on the global rating of change scale of plus three or higher at one year.

The authors therefore concluded that physical therapy did a better job in controlling pain and improving the functional disability at one year and is favored over intra articular corticosteroid injections.  Interestingly the mean cost for all knee related medical care during the one year trial was similar in the two groups.

WHAT ARE THE MAIN TAKE AWAY POINTS FROM THE STUDY?

The trial was designed to compare physical therapy to intra articular corticosteroid injections in patients with symptomatic clinical and radio graphic osteoarthritis in one or both knees and showed that physical therapy was more effective than glucocorticoid injections as assessed by the total WOMAC score and performance of functional tasks.

The advantages of this study is the long duration of follow up since previously short courses of physical therapy for four weeks at a time did show short term benefits but by one year the mean WOMAC scores would regress towards the baseline values.

What we also learned from this trial is the additional impact of educational sessions, periodic follow up visits with clinicians and change in interventions when necessary in managing our knee osteoarthritis patients. A dynamic world it is very similar to Rheumatoid arthritis!!!

Although intra articular corticosteroid injections do offer short term improvement , physical therapy shows both short term and long term benefits.

WILL THIS BE MY STANDARD OF CARE?

As with any trial there are definitely limitations and they are as follows,

• Patients who were assigned to physical therapy arm had more visits with the health care provider than patients assigned to the intra articular corticosteroid injections group.
• Patients had overlapping treatments which might have altered the trial conclusions.
• Significant number of patients in both arms did not meet the primary and secondary outcomes.
• Few patients despite all the interventions had their knees replaced.
• Few patients needed more than three intra articular corticosteroid injections and few patients needed more than the assigned number of physical therapy sessions.
• Most importantly this was an unblinded trial, hence bias cannot be ruled out.

CONCLUSIONS

Although physical therapy for patients with knee osteoarthritis will be the standard of care in my clinical practice, I will not discourage patients from getting intra articular steroid injections.

IMPLICATIONS FOR PATIENTS, PROVIDERS AND RESEARCHERS, CURRENT AND FUTURE

There are so many guidelines for management of knee osteoarthritis laid out by different societies. A treatment algorithm is truly lacking. A brief review is summarized here:

• Osteoarthritis research society international guidelines/OARSI emphasizes on core treatments including:
  • Arthritis education, structured land based exercise programs with and without dietary management, acquatic exercises.
  • Medical management includes topical NSAIDs, oral NSAIDs with PPIs if no contraindications, duloxetine, intraarticular corticosteroids, intra articular hyaluronic acid, topical capsaicin.
  • The society discourages the use of acetaminophen (paracetamol), oral and transdermal opiods.
• American college of rheumatology/ACR foundation recommends:
  • Exercises including balance exercises, weight loss, self efficacy and self management programs, tai chi, yoga, cognitive behavioural therapy.
  • Use of assisted devices like cane, tibiofemoral knee braces, patellofemoral braces, kinesiotaping.
  • Accupunture.
  • Thermal interventions including heat and cold, radiofrequency ablation.
  • Medical management includes topical and oral NSAIDs, intra articular glucocorticoid injections, topical capsaicin, acetaminophen, duloxetine, tramadol.
  • It discourages massage therapy, use of modified shoes and wedged insoles, pulsed vibration therapy, transcutaneous electrical stimulation.
  • It also discourages use of opiods, intra articular hyaluronic acid injections, intra articular botulinum injections, colchicine, fish oils, vitamin d and prolotherapy, platelet rich plasma treatment, stem cell injections, bisphosphonates, glucosamine, chondroitin sulfate, hydroxychloroquine, methotrexate, TNF inhibitors and IL-1 receptor antagonists.
• An American Academy of Orthopaedic Surgeons (AAOS) guideline suggests:
  • Encouraging patients with knee osteoarthritis to participate in self-management educational programs such as those conducted by the Arthritis Foundation and to incorporate activity modifications into their lifestyle (eg, walking instead of running or engaging in alternative activities).
  • The medications recommended are oral and topical NSAIDs,tramadol.
  • No guideline recommendations for use of Intra-articular hyaluronic acid, Glucosamine and/or chondroitin sulfate or hydrochloride.
• A recent review of Diagnosis and treatment of hip and knee osteoarthritis:
  • A review was published in JAMA, authored by Jeffrey N Katz et al, presented a table highlighting many therapies which we continue to use despite recommendations to the contrary. Follow this pubmed link to find the article.
• Well powered randomized controlled trials comparing different treatment options to lay out clear protocols is the need of the hour in osteoarthritis management.

Also worth noting that patients with persistent pain and functional loss and advanced radiographic changes are candidates for total knee replacement (TKR). More than 700 000 primary TKRs are performed annually in the US, more than 90% of which are for OA. 10% of TKRs need to be revised over 20 years. The failure rate is higher in younger and more active recipients, those with comorbidities, and those operated on in low-volume centers or by low-volume surgeons. Obesity, diabetes, chronic pain, anxiety and depression, cirrhosis, hepatitis C, delay in the timing of the TKA all either cause complications or lead to adverse outcomes.

WILL THIS ARTICLE WIN THE FIRST ROUND MATCH UP ? COULD THIS ARTICLE WIN AT ALL? YES I AM HOPEFUL.

• Osteoarthritis is the most common joint disease, affecting an estimated more than 240 million people worldwide, including an estimated more than 32 million in the US.
• Osteoarthritis is the most frequent reason for activity limitation in adults.
• It causes lot of joint dysfunction, pain, stiffness, functional limitation, loss of valued activities, such as walking and exercising.
• Knee osteoarthritis is the most common joint along with hip osteoarthritis which undergoes these changes.
• It is estimated that 30% of individuals older than 45 years have radiographic evidence of knee OA and of these 50% have symptomatic knee OA.
• Osteoarthritis also leads to substantial cost. 43% of the 54 million individuals in the US living with arthritis experience arthritis related limitations in daily activities. Wage losses due to OA amount to 65 billion $ and direct medical costs exceed 100 billion $. Persons with knee OA spend an average of about 15,000 $ over their life times on direct medical costs of OA.
• Osteoarthritis is commonly associated with comorbidities, which many stem from lack of physical activity, medication toxicity, and effects of inflammatory cytokines.
• Persons with knee OA have approximately 20% excess mortality compared with age matched controls, in part because of lower levels of physical activity.
• I am hoping that I have justified how important this study is in our day to day clinical practice.

References

1. Deyle et al. Physical Therapy versus Glucocorticoid Injection for Osteoarthritis of the Knee. NEJM.2020;382(15):1420-29 (pubmed link)
2. Jeffrey Katz et al. Diagnosis and Treatment of Hip and Knee Osteoarthritis. JAMA 2021;325(6):568-78. (pubmed link)
3. Guidelines for management of osteoarthritis by ACR,OARSI,AAOS

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