Low-Dose Methotrexate Plus Adalimumab Yields Similar PROs to High-Dose Treatment

May 3, 2018
The Center for Biosimilars Staff

While adalimumab and methotrexate are understood to have a synergistic effect, the MUSICA trial sought to evaluate the ideal dose of methotrexate needed in patients who receive combination therapy for rheumatoid arthritis.

Although methotrexate is recommended as first-line treatment for patients with moderate to severe rheumatoid arthritis (RA), those patients who do not have an adequate response to methotrexate alone may have an anti—tumor necrosis factor therapy, such as adalimumab, added to their treatment. While adalimumab and methotrexate are understood to have a synergistic effect, the MUSICA trial sought to evaluate the ideal dose of methotrexate needed in patients who receive combination therapy.

Reporting on their results in Rheumatology and Therapy, investigators explained that they assessed a reduced methotrexate dose of 7.5 mg per week versus a high dose of 20 mg of methotrexate per week in 309 patients who previously had received doses of at least 15 mg per week.

Although the primary endpoint of the MUSICA study—the mean 28-joint disease activity score based on C-reactive protein at week 24—was not met, patient-reported outcomes (PROs) were also recorded weekly to week 24. In total, 154 patients were randomized to the low dose plus adalimumab group and 155 patients to the high dose plus adalimumab group.

The researchers found the following concerning PROs:

  • Improvements were observed in both groups, with the greatest improvement demonstrated within 12 weeks and maintained to week 24.
  • Both groups showed statistically significant, clinically meaningful improvements in physical function form baseline as measured by the Health Assessment Questionnaire-Disability Index, with no statistically significant difference between the 2 groups.
  • Mean improvements from baseline to week 24 in the correlation of physical or mental well-being with sleep were slightly higher in the high-dose group.
  • Both groups showed rapid improvement by week 4, maintained to week 24, in work productivity and regular activity impairment.
  • At week 24, improvements were observed in all subdomains of the Treatment Satisfaction Questionnaire for Medication in both groups, except in the subdomain of medication convenience.
  • Significant improvement was demonstrated in most subdomains of Medical Outcomes Study scale for sleep in both groups, with no statistically significant differences between the groups.
  • A statistically significant improvement in sexual impairment from baseline was observed in both groups at week 24.

The authors concluded that both high- and low-dose groups showed rapid, significant improvements in PROs from baseline to week 24, and for many of these PROs, these improvements were comparable at both doses.

Reference

Kaeley GS, MacCarter DK, Goyal JR, et al. Similar improvements in patient-reported outcomes among rheumatoid arthritis patients treated with two different doses of methotrexate in combination with adalimumab: results from the MUSICA trial [published online March 24, 2018]. Rheumatol Ther. doi: 10.1007/s40744-018-0105-7.