Compared with an infusion into the vein, injecting Actemra (tocilizumab) under the skin offers people with systemic and polyarticular juvenile idiopathic arthritis (JIA) similar performance in a more convenient route of administration, according to data from clinical trials.
Notably, the subcutaneous or under-the-skin injection method “has potential for in-home use,” the researchers said.
The study, “Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis,” was published in the journal Rheumatology.
It showed that under-the-skin Actemra “provides exposure and risk/benefit profiles similar to those of IV” or intravenous (into the vein) administration.
Actemra blocks the action of the IL-6 protein, which plays a central role in JIA, correlating with the severity of a patient’s joint involvement and other features of the disorder. The medication has been approved in the U.S. to treat polyarticular (pJIA) and systemic JIA (sJIA), as well as rheumatoid arthritis and giant cell arteritis, an inflammation of the lining of the arteries.
Marketed by Genentech (part of the Roche group), it can be given intravenously or subcutaneously. Two Roche-sponsored Phase 1b trials were conducted to identify optimal dosing regimens.
The trials (NCT01904292 and NCT01904279) tested subcutaneous Actemra in children with sJIA or pJIA, a harder-to-treat type of JIA with more joint involvement and a higher risk for severe disability. Specifically, Actemra was given in a 162 mg dose to sJIA patients every week or every two weeks, and to pJIA children every two or three weeks. Children with either disease type received the more frequent dosing regimen if their weight was 30 kg (66.1 lbs) or more.
The studies, both two years long, recruited 51 sJIA and 52 pJIA participants, all ages 1 to 17. Of the sJIA patients, 44 (86%) completed their respective study, as did 46 (89%) of those with pJIA.
In sJIA and pJIA participants who had never used the medication before — called Actemra-naïve — concentrations reached stable levels around weeks 12 to 14. Patients switching from IV to subcutaneous Actemra maintained their blood levels of the medication.
Subcutaneous Actemra reached largely the same steady-state concentration in patients’ blood as did the IV-administered medicine.
Disease activity among Actemra-naïve patients, as measured by the Juvenile Arthritis Disease Activity Score (JADAS-71), showed similar improvements to those seen with the IV formulation. Also, JADAS-71 values held steady among participants switching from IV to subcutaneous formulation, indicating that changing delivery routes maintained the same level of efficacy.
By the end of the studies, a number of sJIA and pJIA patients achieved clinical remission, and most achieved inactive disease and decreased their glucocorticoid therapy needs.
The safety of the subcutaneous injection appeared consistent with that of the IV formulation, with the exception of injection site reactions, reported among 41.2% of children with sJIA and 28.8% of those with pJIA.
Most side effects were considered of mild to moderate intensity, and unrelated to treatment.
The most common side effect reported was infections, occurring most often in patients under 30 kgs than in those weighing 30 kgs or more: 88% vs. 69.2% among sJIA children, and 74.1% vs. 64% among those with pJIA.
Nine serious adverse events occurred in seven sJIA patients and four occurred in three pJIA patients. The nine sJIA individuals collectively experienced five serious infections, two sJIA flares, vertigo, and pulmonary bleeding, while the three pJIA participants reported croup, chickenpox, worsening anorexia, and joint pain.
Two children with sJIA died while participating in the study and both deaths were considered related to Actemra. One had pneumonia and oral candidiasis, also called oral thrush, and died of a pulmonary hemorrhage on day 15 after receiving a single TCZ dose on day 1. Another patient died of suspected sepsis on day 262, or nearly nine months into the trial. Both patients were receiving concomitant steroids and other medications
No serious hypersensitivity to treatment or immune reactions were observed.
Overall, the dosing regimens established in these trials for subcutaneous Actemra provided comparable safety and exploratory efficacy as the IV formulation, and are currently approved for children with sJIA or pJIA in the U.S. and Europe.
“[Subcutaneous Actemra] provides exposure and risk/benefit profiles similar to those of IV [Actemra],” the investigators wrote, adding that it “provides an alternative administration route that is more convenient for patients and caregivers and that has potential for in-home use.”