Background Tocilizumab, an IL-6 receptor antagonist, is one of the essential biologics for the treatment of rheumatoid arthritis (RA) patients. Several adverse effects have been reported after tocilizumab infusion, but occurrence of myalgia has rarely been discussed. We observed several RA patients who complained myalgia after tocilizumab treatment.
Objectives We conducted this study to examine which patients developed myalgia and whether biologics other than tocilizumab can induce myalgia.
Methods RA patients who had inadequate response to MTX were treated by 8mg/kg of tocilizumab every 4 weeks or 3mg/kg of infliximab at weeks 0, 2, 6, 14, and every 8 weeks thereafter. Patient’s myalgia and global status were evaluated everyday by themselves using 0 to 100 mm visual analog scales (VAS). Global status was also assessed by physician at patient’s every visit to the hospital. Serum IL-6 of them were examined at baseline and every 4 weeks at tocilizumab infusion. The serum levels of CRP, creatine kinase (CK), aldolase, and TNF-α were also examined in addition to regular blood tests and DAS28 score were calculated. Ultrasound or MRI was examined in some patients who emerged myalgia.
Results Fourty-nine RA patients were treated with tocilizumab and 44 with infliximab. Of tocilizumab treated patients, 14 complained myalgia but no patients of infliximab did. The myalgia started one or two days after receiving tocilizumab infusion and decreased gradually. The myalgia recurred by next tocilizumab infusions although the magnitude was smaller. They suffered from severe myalgia of upper body such as neck, shoulder, and back muscles, but these pains were quite different from those of fibromyalgia, polymyalgia rheumatica, or viral infection. When the patients complained myalgia, the levels of CRP had decreased to basal levels (less than 3 mg/L) and their activities of RA such as swelling joints counts were rather decreased. RA patients with high disease activity at initial tocilizumab treatment developed myalgia more frequently than those with low disease activity. In the patients experienced myalgia, the serum IL-6 levels were significantly higher (94±61 pg/L) than those in patients without myalgia (32±20 pg/L) at 28 days after initial tocilizumab treatment. But the serum levels of high sensitive TNF-α and CRP were decreased to within normal limits, and the levels of CK or aldolase were within normal range. Ultrasound or MRI at the site of myalgia showed normal image and no inflammatory sign. After initial tocilizumab treatment, the magnitude of myalgia decreased well paralleled with serum IL-6 levels.
Conclusions The RA patients treated with tocilizumab frequently experienced myalgia but did not with infliximab in case of high disease activity. In the patients who complained myalgia, the levels of IL-6 but not CRP or TNF-α were selectively high in spite of decreasing the disease activities. Before tocilizumab treatment, the patients did not complain myalgia, when both IL-6 and CRP levels were high, suggesting the myalgia supposed due to interaction of IL-6 and tocilizumab and not to TNF-α associated interaction.
Disclosure of Interest None Declared