Home > Rheumatology > ACR 2020 > Osteoarthritis – Novel Developments > Knee osteoarthritis patients with indicators of inflammation could profit from methotrexate

Knee osteoarthritis patients with indicators of inflammation could profit from methotrexate

Presented by
Prof. Biswadip Ghosh, Institute of Post Graduate Medical Education and Research, India
ACR 2020
Patients with osteoarthritis and signs of inflammation showed benefit when treated with methotrexate. In a new trial, improvements were observed in both systemic markers of inflammation and also joint function.

The concept of local as well as systemic inflammation increasing joint impairment in osteoarthritis (OA) seems increasingly acknowledged [1]. “We see patients with OA almost every day who are usually advised non-pharmacological interventions and analgesics only, until the pain is unbearable and then they are asked to go for knee replacement,” Prof. Biswadip Ghosh (Institute of Post Graduate Medical Education and Research, India) described the current situation [2]. “Most patients suffering from knee OA have episodes of inflammation and each episode not only increases the pain but also further damages the joint,” he further pointed out.

The presented trial assessed the efficacy of methotrexate versus glucosamine as a substitute for placebo in adults with primary radiographic-confirmed OA of the knee and joint swelling as well as pain for ≥6 months.

Based on erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels at baseline, 249 patients were assigned to an inflammatory group (n=172) or a non-inflammatory group (n=77). Among the exclusion criteria were Kellgren and Lawrence grade-4 OA, recent intra-articular injections, and uncontrolled metabolic conditions such as diabetes or gout.

Patients assigned to the inflammatory group of the trial had either increased ESR (>30 mm/hour) and CRP (>1.5 times the reference value) on 1 occasion or 1 of the parameters measured at 2 separate moments that were 1 month apart. Patients in this group also underwent further diagnostic imaging with musculoskeletal ultrasound, X-ray, and MRI. Patients in the inflammatory group were then randomised to treatment with methotrexate or glucosamine with a follow-up time of 3 months.

Baseline demographics showed a mean age of 51.9 versus 51.6 and a Western Ontario and McMaster Universities Arthritis Index (WOMAC) of 45.20 versus 49.356 in the non-inflammatory versus the inflammatory group, respectively.

Within the methotrexate-treated part of the inflammatory group, ESR was significantly decreased compared with baseline (P=0.0007). Moreover, WOMAC decreased from a mean of 52 at baseline to a mean of 38 after methotrexate treatment (P<0.0001), indicating better physical function. In the patients in the inflammatory group that were treated with glucosamine, changes in ESR and WOMAC were not significant.

“In conclusion, we should look for inflammation in symptomatic primary knee OA patients and if found, we should treat it with anti-inflammatory agents,” recommended Prof. Gosh. He suggested that methotrexate may be considered in such patients if conventional treatments fail, but also pointed to the need for more research regarding the role of inflammation in knee OA patients.


  1. Scanzello CR, Loeser RF. Arthritis Rheumatol. 2015;67:2797-800.
  2. Gosh B, et al. Comparison of Methotrexate and Glucosamine in Primary Knee Osteoarthritis with Inflammation. P1648, ACR Convergence 2020, 5-9 Nov.

Posted on