Tocilizumab efficacy in RA not affected by comorbidities, obesity status

Tocilizumab is a common treatment for rheumatoid arthritis (RA) patients with comorbid conditions or obesity and is effective irrespective of comorbidity burden or obesity status, according to a study.

“Using data from the largest US-based RA registry, we demonstrated that patients who initiated tocilizumab improved in Clinical Disease Activity Index and Health Assessment Questionnaire at 6 and 12 months, with similar improvements in patients with high and low comorbidity burden and obese and nonobese patients,” the researchers said.

This study stratified patients in the Corrona RA registry who initiated tocilizumab by low or high comorbidity burden using a modified Charlson Comorbidity Index (mCCI) and by obese or nonobese status using body mass index (BMI).

The researchers then compared improvements in disease activity and functionality after tocilizumab initiation for the above strata of patients at 6 and 12 months after adjusting for statistically significant differences in baseline characteristics.

Overall, 195 and 575 patients with high (mCCI ≥2) and low (mCCI <2) comorbidity burden, respectively, as well as 356 obese (BMI ≥30) and 449 and nonobese (BMI <30) patients who were treated with tocilizumab were included in the analysis. [J Rheumatol 2020;47:1464-1474]

More than 95 percent of patients had failed other biologics and nearly one-third had received tocilizumab as monotherapy, with no significant differences seen between them either by comorbidity burden or obesity status. Of note, improvement in disease activity and functionality at 6 and 12 months was similar between groups regardless of comorbidity burden or obesity status.

“The current study provides insight into tocilizumab use in real-life practice in the US,” the researchers said. “We found tocilizumab is frequently used in patients with comorbidities and obesity, as 25 percent of tocilizumab initiators in our study had a high mCCI and 45 percent were categorized as obese.”

Most patients received intravenous (IV) tocilizumab 8 mg/kg at 6 months postinitiation. Administration of the study drug on a mg/kg basis might have allowed rheumatologists to more easily modify dose based on patients’ weight or lack of response to the recommended initial dosing of 4 mg/kg every 4 weeks (increasing to 8 mg/kg based on clinical response).

“Thus, the dose flexibility of tocilizumab may have improved disease control in patients who would have been nonresponders if treated with a biologic not adjusted for body weight,” the researchers said.

Patients with a higher comorbidity burden are less likely to start biologic treatment early in their disease course. Obesity, on the other hand, has been associated with poorer clinical outcomes in RA patients. In addition, weight negatively impacts the efficacy of tumour necrosis factor inhibitors. [Medicine 2018;97:e9930; Clin Exp Rheumatol 2015;33:478-483; Arthritis Care Res 2013;65:78-87; Autoimmun Rev 2016;15:447-450; Joint Bone Spine 2015;82:187-191; RMD Open 2017;3:e000458]

The current study had certain limitations. Tocilizumab effectiveness was not separately analysed for patients with more than two comorbidities and in those with extreme obesity or with weight >100 kg.

“Thus, these results should be interpreted with caution for patients with multiple comorbidities or extreme obesity,” the researchers noted.