No Rise in Cancer Risk with Actemra Save

In patients with rheumatoid arthritis (RA), there was no increased risk for malignancy development seen with newly initiated tocilizumab (Actemra) treatment, an analysis of three U.S. insurance claim databases found.

Among patients newly starting tocilizumab enrolled in Medicare, IMS PharMetrics Plus, and Truven MarketScan, the combined risk for any new cancers except nonmelanoma skin cancer wasn't significantly different compared with TNF inhibitor initiators (HR 0.98, 95% CI 0.80-1.19), Seoyoung C. Kim, MD, ScD, of Brigham and Women's Hospital in Boston, and colleagues reported online in Seminars in Arthritis & Rheumatism. 

Broken down by individual insurance database, the risk of any new cancer excluding nonmelanoma skin cancer with newly initiated tocilizumab initiators versus newly initiated TNF inhibitors were as follows:

• Medicare: HR 1.05 (95% CI 0.81-1.37)
• IMS: HR 0.80 (95% CI 0.52-1.24)
• MarketScan: HR 0.97 (95% CI 0.64-1.47)

There also weren't any significantly increased risks for tocilizumab compared with TNF inhibitors when looking at individual malignancies:

• Non-Hodgkin's lymphoma: HR 1.31 (95% CI 0.60-2.88)
• Bladder cancer: HR 1.32 (95% CI 0.40-4.31)
• Breast cancer: HR 1.39 (95% CI 0.92-2.10)
• Colorectal cancer: HR 0.82 (95% CI 0.26-2.53)
• Lung cancer: HR 1.0 (95% CI 0.61-1.65)

"With [an] increasing number of patients starting a biologic DMARD or switching to a different biologic DMARD for RA in recent years, our findings of low absolute risk for malignancies, which is comparable across different biologic DMARDs, are reassuring to both patients and their providers," Kim and colleagues wrote.

Patients with RA are at increased risk of certain cancers, such as lymphoma and lung cancer, and biologic therapies that target the immune system could interfere with tumor surveillance. Previous work is generally reassuring about cancer risks with TNF inhibitors, but less is known about risks with other newer types of biologics such as tocilizumab -- an interleukin 6 receptor blocker -- and abatacept (Orencia), which binds to the CD80/CD86 molecule preventing T-cell activation.

Accordingly, Kim and colleagues conducted a cohort study of RA patients who had previously used one or more biologics or the JAK inhibitor tofacitinib (Xeljanz) and were newly starting tocilizumab or a TNF inhibitor. For a secondary analysis, they also considered patients newly starting abatacept (Orencia).

The study included a yearlong period prior to the treatment initiation, during which multiple variables were assessed, including comorbidities, severity and duration of RA, and use of other medications. These characteristics were used for propensity score matching.

The primary analysis included 13,102 patients receiving tocilizumab and 26,727 given TNF inhibitors, and the secondary analysis included 8,465 matched pairs of patients receiving either tocilizumab or abatacept.

Patients' mean ages were 72 in Medicare, 53 in MarketScan, and 51 in IMS, the majority of which were female and almost three-quarters of all databases used methotrexate. Comorbidities and other drug use were more common in the Medicare group.

During a combined 11,013 person-years of follow-up among the tocilizumab group, there were 153 malignancies compared with 325 malignancies during the in 24,137 person-years among the anti-TNF group. The incidence rates in the tocilizumab group ranged from 8.27 per 1,000 person-years in IMS to 23.18 per 1,000 in Medicare, and from 9.64 per 1,000 in IMS in MarketScan to 21.46 per 1,000 in Medicare for the anti-TNF group.

In the secondary analysis, there were 101 malignancies during 7,155 person-years in the tocilizumab group and 111 during 7,336 person-years in the abatacept group, for combined incidence rates of 14.12 per 1,000 for tocilizumab and 15.13 per 1,000 for abatacept. The hazard ratio for any malignancy except nonmelanoma skin cancer was 0.97 (95% CI 0.74-1.27) for tocilizumab versus abatacept.

These data were similar to what was reported in a recent Swedish study, in which incidence rates were 9.2 per 1,000 person-years for TNF inhibitors, 9.6 per 1,000 for tocilizumab, and 10.3 per 1,000 for abatacept.

"In conclusion, this population-representative cohort study found no difference in the risk of incident malignancies among RA patients who switched from a biologic DMARD or tofacitinib to tocilizumab compared to those who switched to a different TNF inhibitor or abatacept," the authors stated.

Limitations to the analysis included lack of information about factors such as family history, body mass index, or smoking.

The study was funded by Roche.

The authors reported financial relationships with Roche, Pfizer, Bristol-Myers Squibb, AstraZeneca, Genentech, Amgen, CORRONA, Merck, Vertex, WHISCON, Aetion, and Boehringer Ingelheim.