Purpose: Intra-articular corticosteroid injections is a well established treatment for knee osteoarthritis (OA). However, only 60% of patients have a good short-term response and about 20% of patients have a satisfactory long-term response. Genetic variants may play a role in predicting response to corticosteroids. A genetic variant of the macrophage inflammatory factor (MIF) (a physiologic counter-regulator of glucocorticoids), has been associated with poor clinical response in various inflammatory diseases. No studies to date have evaluated the effect of this variant on steroid injections for knee OA. We set out to determine the impact of the – 173(C) variant of the MIF gene on clinical response to intra-articular injections for knee OA.

Method: 80 patients with Kellgren-Lawrence Grade 2–3 OA of the knee were prospectively followed for three months following a standard dose of steroid injection. All patients were genotyped for the – 173 variant of the MIF gene. WOMAC questionnaires for knee OA were done at baseline, one, four and twelve weeks to assess response to treatment.

Results: 21 patients (25%) carried the C allele of – 173 variant of the MIF gene. At 12 weeks, patients with the C variant had a statistically significant decrease in the pain dimension of the WOMAC compared to the G variant. Similar responses were not obtained at weeks one and four.

Conclusion: A specific polymorphism in the MIF gene appears to be associated with a poor response to intra-articular knee injections. Further validation is required with larger sample sizes to assess the impact of prospectively genotyping for this variant prior to knee injections.

The efficacy of intra-articular corticosteroids has led to their frequent use in the treatment of osteoarthritis (OA) of the knee. It is commonly believed that less soluble preparations given at higher doses provide longer lasting and more significant symptomatic relief. We performed a randomized controlled trial with corticosteroid preparations of different solubilities and dosages to test this longstanding but unproven belief. The pain subscale of the WOMAC was our primary outcome measurement. This study found no statistically significant difference between preparations or dosages. Regression analysis identified early onset of osteoarthritis as predictive of a positive treatment response.

To determine if the solubility or dosage of an intra-articular corticosteroid preparation effects treatment outcome when used for the treatment of symptomatic osteoarthritis of the knee.

One hundred and seventeen patients, thirty-nine in each treatment arm, were enrolled in the study. Patients were randomly assigned to one of three treatment arms: 40mg of methylprednisolone acetate, 80mg of methyl-prednisolone acetate or 40mg Triamcinolone acetanide. Patients were unaware of the preparation given. The IA injection was given at the commencement of the study period. Patients underwent clinical evaluation at baseline and at two weeks, four weeks and twelve weeks post injection. Patient’s symptoms were evaluated using the Western Ontario and McMaster Universities OA Index (WOMAC). Patient age, sex, age of onset of OA, history of trauma to the knee and BMI were also recorded and used to identify patient variables predictive of a positive treatment response.

No statistically significant difference between the three treatment arms was identified. Early onset of OA was identified as predictive of a positive treatment response.

It has been taught that physicians should use the least soluble preparation at higher doses (within suggested guidelines) to maximize patient treatment response when using intra-articular corticosteroids. This has always been based on theory and not fact. Our study is the first to scientifically disprove this claim. Solubility and dosage do not effect treatment outcomes. Patients with an early onset of OA seem to have a positive treatment response.

Ours is the first study to demonstrate these findings.