Session Information
Date: Monday, November 9, 2015
Title: Rheumatoid Arthritis-Small Molecules, Biologics and Gene Therapy IV: Safety of Targeted Therapies
Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose:
Immune incompetence may lower host surveillance against incipient tumours. Conversely, immune therapies have emerged as a promising therapeutic approach to cancer. Malignancies thus constitute an important aspect of the safety of biologics as used in Rheumatology, including agents targeting TNF, CD20, CTLA-4, and IL6. Previous reports concerning TNF inhibitors (TNFi) and risk of malignancies have mostly been reassuring. The risk of malignancies among RA patients treated with non-TNFi biologics is less well-known.
Methods:
Through linkages of Swedish national and population-based registers we assembled three cohorts of patients with RA initiating a first ever treatment of: 1) rituximab, 2) abatacept, 3) tocilizumab, 4) any TNFi, and 5) a cohort initiating a second TNFi. Also, 6) a biologics-naïve RA cohort was assembled, and 7) a general population comparator cohort, matched 1:10 on the biologics-naïve RA cohort. Through linkage with the Cancer Register information on cancer events were gathered. Outcomes were defined as first solid invasive malignancy, first hematologic malignancy, first invasive squamous cell skin cancer, and first solid or hematologic malignancy, all defined as first during follow-up. Patients were followed from treatment start until death, emigration, outcome or end of follow up. Crude incidences, as well as age and sex standardized incidences were calculated for outcomes from 2006 through 2012. Hazard ratios were calculated using Cox-regression, adjusted for age and sex.
Results:
Adjusted for age and sex, there were no statistically significant differences, for any of the outcomes, between initiators of non-TNFi biologics and initiators of a first or second TNFi, although small number of events precluded formal comparisons in some of the analyses.
Conclusion: The overall risk of malignancies among RA patients initiating rituximab, abatacept, or tocilizumab in clinical practice does not differ substantially from that of RA patients initiating a first or second TNF inhibitor, though risks for specific cancer sites or with longer latency cannot be excluded.
Table. Number of persons, events, crude incidence, standardized incidence, average follow-up time and hazard ratios for the different outcomes under study.
|
Outcome definition |
Cohort |
Number of persons at risk |
Number of events |
Crude incidence per 100,000 pys |
Incidence rate standardized to the non-tnfi bio cohorts (by age and sex) |
Mean follow-up, years |
HR (adjusted for age and sex) |
|
|
|
|
|
|
|
|
|
|
First invasive solid cancer |
1 rituximab |
2048 |
62 |
1028 |
1013 |
2.94 |
1.05 (0.82-1.34) |
|
2 abatacept |
622 |
12 |
787 |
832 |
2.45 |
0.86 (0.49-1.51) |
|
|
3 tocilizumab |
630 |
13 |
1186 |
1302 |
1.74 |
1.33 (0.77-2.30) |
|
|
4 First TNFi |
7389 |
189 |
849 |
977 |
3.01 |
1.03 (0.89-1.18) |
|
|
5 Second TNFi |
3120 |
71 |
858 |
986 |
2.65 |
1.05 (0.83-1.33) |
|
|
6 Biologics-naïve RA |
43 523 |
2181 |
1212 |
1033 |
4.13 |
1.07 (1.02-1.12) |
|
|
7 General population |
387 480 |
20172 |
1074 |
960 |
4.85 |
REF |
|
|
|
|
|
|
|
|
|
|
|
First hematologic malignancy |
1 rituximab |
2048 |
5 |
82 |
84 |
2.98 |
1.08 (0.45-2.60) |
|
2 abatacept |
622 |
4 |
260 |
258 |
2.47 |
NA |
|
|
3 tocilizumab |
630 |
0 |
0 |
0 |
1.76 |
NA |
|
|
4 First TNFi |
7389 |
21 |
93 |
99 |
3.05 |
1.51 (0.98-2.32) |
|
|
5 Second TNFi |
3120 |
10 |
120 |
149 |
2.68 |
1.96 (1.05-3.65) |
|
|
6 Biologics-naïve RA |
43 524 |
275 |
150 |
124 |
4.22 |
1.58 (1.39-1.80) |
|
|
7 General population |
387 488 |
1694 |
88 |
74 |
4.95 |
REF |
|
|
|
|
|
|
|
|
|
|
|
First invasive squamous cell skin cancer |
1 rituximab |
2048 |
9 |
147 |
135 |
2.98 |
2.23 (1.16-4.29) |
|
2 abatacept |
622 |
2 |
130 |
180 |
2.48 |
NA |
|
|
3 tocilizumab |
630 |
1 |
90 |
90 |
1.76 |
NA |
|
|
4 First TNFi |
7389 |
25 |
111 |
145 |
3.05 |
2.36 (1.59-3.50) |
|
|
5 Second TNFi |
3120 |
5 |
60 |
72 |
2.68 |
1.27 (0.53-3.05) |
|
|
6 Biologics-naïve RA |
43526 |
330 |
180 |
116 |
4.22 |
1.67 (1.48-1.88) |
|
|
7 General population |
387 485 |
1819 |
95 |
73 |
4.95 |
REF |
|
|
|
|
|
|
|
|
|
|
|
First invasive solid or hematologic cancer |
1 rituximab |
2048 |
66 |
1096 |
1086 |
2.94 |
1.04 (0.82-1.32) |
|
2 abatacept |
622 |
16 |
1052 |
1096 |
2.45 |
1.07 (0.66-1.75) |
|
|
3 tocilizumab |
630 |
13 |
1186 |
1309 |
1.74 |
1.25 (0.72-2.14) |
|
|
4 First TNFi |
7389 |
208 |
936 |
1078 |
3.01 |
1.06 (0.92-1.21) |
|
|
5 Second TNFi |
3120 |
81 |
981 |
1143 |
2.65 |
1.12 (0.90-1.39) |
|
|
6 Biologics-naïve RA |
43521 |
2440 |
1360 |
1161 |
4.12 |
1.11 (1.06-1.16) |
|
|
7 General population |
387 480 |
21735 |
1160 |
1037 |
4.84 |
REF |
To cite this abstract in AMA style:
Wadström H, Askling J. Risk of Cancer in Non-TNFi Biologics-Treated RA [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/risk-of-cancer-in-non-tnfi-biologics-treated-ra/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/risk-of-cancer-in-non-tnfi-biologics-treated-ra/