Methotrexate improves function in people with knee OA after 3 months

Methotrexate improves function in people with knee OA after 3 months

ATLANTA — A new study presented at ACR Convergence, the American College of Rheumatology’s annual meeting, shows that after three months of treatment with oral methotrexate, adults with primary knee osteoarthritis (OA) with inflammation had significant improvements in physical function and inflammation, a sign that this inexpensive, generic pill may be an important intervention for knee OA (ABSTRACT #1648).

OA is a common joint disease that most often affects middle age to older people. It is commonly referred to as “wear and tear” of the joints, but it is now known that OA is a disease of the entire joint, involving the cartilage, joint lining, ligaments, and bone.

Many people with knee OA show clinical signs of joint inflammation, including swelling, warmth and pain. Although inflammation may play a major role in pain and loss of function and progressive damage in joints with OA, there are no current, accepted drug therapies to address the condition in these patients. This study, which was conducted by researchers at SSKM Hospital in Kolkata, India, compared oral methotrexate to placebo treatment with glucosamine, a common supplement for arthritis pain relief, in adults with primary knee OA.

“Almost all patients with primary knee OA experience periods of warmth and swelling in the joint, with increases in pain and reduction of function,” says the study’s co-author, Biswadip Ghosh, MD, associate professor, Department of Rheumatology, at Institute of Post Graduate Medical Education and Research in Kolkata, India. “Those episodes are inflammation, and every episode damages the structures of the knees a little more. After some time, swelling subsides partly due to burning out of materials. That leaves the knee in a hopeless state of function loss where physiotherapy helps minimally with enlistment for knee replacement. It will be helpful for patients if we can decrease the inflammation and rescue the joint,” says Dr. Ghosh.

Male and female patients with primary knee OA who had swelling and pain in both knee joints for at least six months, and also had evidence of OA on their X-rays, were recruited for the study. Researchers excluded anyone with advanced OA or secondary OA; anyone who had undergone arthroscopy (a procedure for diagnosing and treating joint problems) ; intra-articular steroid injection in the previous three months; or patients who had uncontrolled diabetes, renal or hepatic diseases, or gout.

Patients with signs of local inflammation, such as pain and swelling of the whole knee with warmth, were checked for erythrocyte sedimentation rate and C-reactive protein blood levels. Any patient with increases in both inflammatory markers on one exam or either on two exams held one month apart was placed in an inflammatory group in the study. Other patients were placed in a non-inflammatory group.

Blood samples collected from all the patients and healthy controls were tested for selected biomarkers of osteoarthritis. Patients in the inflammatory group of primary knee OA were screened for other inflammatory arthritis with a clinical exam, blood tests, musculoskeletal ultrasound and X-ray, as well as MRI scans of their knees. Patients in the inflammatory group were then randomly allocated to take 15-20 mg/week of oral methotrexate or 1,500 mg/day of glucosamine as a placebo, then checked once a month for three months. Patients were allowed to take acetaminophen or tramadol for pain if needed and were also given NSAIDs for 7-10 days at the beginning of the study to improve compliance.

A total of 344 people with primary knee OA were included and examined from July 2016 to June 2019. The researchers found that 249 patients had local inflammation, or swelling with pain and warmth in both knees, and 172 of those 249 had elevated erythrocyte sedimentation rate and/or C-reactive protein, both markers at one exam or either marker at two exams held at one month apart. The study’s results showed that patients with primary knee OA with evidence of inflammation had significant improvements on their WOMAC scores, a widely used measurement of physical function, and erythrocyte sedimentation rate and C-reactive protein after three months of taking oral methotrexate. Patients who took glucosamine had no significant improvement in these measures of function and inflammation. This new data suggests that methotrexate can be an effective intervention for people with knee OA who experience pain and inflammation.

“Treatments offered to patients with primary knee OA are usually physical support and knee replacement, which are basically directed to manage the effect of the disease. Our study provides hope to patients not only from this inexpensive molecule, methotrexate, but other therapies directed towards one cause of the disease: inflammation,” says Dr. Ghosh. “We should think of using methotrexate if we find signs of both local and systemic inflammation in patients with primary knee OA when conventional therapies are not helpful. Additionally, more research should be directed towards the inflammatory pathways of the disease in the future.”


About ACR Convergence

ACR Convergence, the ACR’s annual meeting, is where rheumatology meets to collaborate, celebrate, congregate, and learn. Join ACR for an all-encompassing experience designed for the entire rheumatology community. ACR Convergence is not just another meeting – it’s where inspiration and opportunity unite to create an unmatched educational experience. For more information about the meeting, visit, or join the conversation on Twitter by following the official hashtag (#ACR20).

About the American College of Rheumatology

The American College of Rheumatology (ACR) is an international medical society representing over 7,700 rheumatologists and rheumatology health professionals with a mission to empower rheumatology professionals to excel in their specialty. In doing so, the ACR offers education, research, advocacy and practice management support to help its members continue their innovative work and provide quality patient care. Rheumatologists are experts in the diagnosis, management and treatment of more than 100 different types of arthritis and rheumatic diseases.

ABSTRACT: Comparison of Methotrexate and Glucosamine in Primary Knee Osteoarthritis with Inflammation


Many patients suffering from knee OA show swelling, warmth along with pain which are features of inflammation. There are no accepted pharmacological therapy for osteoarthritis that target inflammation though inflammation plays a crucial role in pain generation and progressive joint damage.

There are some evidence that Methotrexate may be useful in knee osteoarthritis. The latest ACR recommendation for OA is not in favour of MTX, but it seems they have more weight to the evidence in case of hand OA than knee OA. ACR recommendation found no evidence of usefulness of glucosamine also, another very commonly used drug for knee OA.

We decided to evaluate the effect of methotrexate in primary knee OA with inflammation in comparison with glucosamine as placebo.


Primary knee OA of both sex, aged 40-65 years, having swelling and pain of both knee joints for at least six months with radiographic OA and consent to study were recruited. Exclusion criteria consisted of KL grade 4, secondary OA, arthroscopy or intra articular injections in last three months, uncontrolled Diabetes, renal, hepatic diseases or gout. Patients with signs of local inflammation i.e. pain swelling of whole knee and warmth were checked for ESR and CRP. If there was increase in both in one occasion or either of them in two occasions 1 month apart (ESR >30mm/1st Hr and CRP >1.5 times of reference), they were placed in systemic Inflammatory group.

Others were placed in non-inflammatory group. Blood was collected from all patients and healthy controls for testing of selected biomarkers. Patients in the inflammatory group were stringently screened for Inflammatory arthritis by clinical examination, blood tests, Musculoskeletal ultrasound, X-ray. MRI of knee was done in all patients of Inflammatory group. Then, patients of inflammatory group were randomly allocated to receive Methotrexate (15-20 mg/week) or Glucosamine (placebo) and followed monthly for three months. All patients were allowed to take paracetamol and tramadol on as needed basis. NSAIDs were given in the beginning for 7-10 days to improve compliance. WOMAC (CRD Pune version) was measured at beginning and end of three months.


Total 344 primary knee OA patients who fulfilled the inclusion and exclusion criteria, were examined from July 2016 to June 2019 in Department of Rheumatology, IPGME&R and SSKM Hospital, Kolkata.
249 patients had local inflammation (swelling of both knees). 172 patients of them had elevated ESR/CRP, both in one occasion or either of them in two occasions 1 month apart.

Table 1: Demography

Table 2: Patients suffering from primary knee OA with inflammation receiving MTX

Table 3: Patients suffering from primary knee OA with inflammation receiving Glucosamine


We found significant improvement in WOMAC, ESR and CRP in patients suffering from primary knee OA with inflammation after three months of taking methotrexate while there was insignificant effect with glucosamine, used as placebo. Our study provides proof that oral Methotrexate may be an important intervention in primary knee osteoarthritis with inflammation.

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