Background/Purpose: The risk of lymphoma is increased in people with RA compared to the general population and is greatest in severe RA. Anti-TNF therapy is now widely used to treat RA, especially severe RA. The aim of this study was to determine whether anti-TNF influences the risk of lymphoma when used in routine UK clinical practice.
Methods: The analysis was conducted in the BSRBR-RA, a national cohort study. Patients with RA starting treatment with the TNF inhibitors etanercept (ETA), infliximab (INF) or adalimumab (ADA) and a biologic-naïve comparison cohort exposed to non-biologic therapy (nbDMARD) were recruited between 2001-2009. Subjects were followed until 09/30/2010, first lymphoma or death, whichever came first. Subjects with a history of lymphoproliferative malignancy prior to registration were excluded. Incident cancers were identified in 3 ways; lifelong flagging with national cancer agencies; 6 monthly patient and physician questionnaires for 3 years and annual physician questionnaires thereafter. Only first lymphoma per subject, confirmed by histology or cancer agency, was analysed. The rates of lymphoma and non-Hodgkin lymphoma (NHL) in the nbDMARD cohort and in patients ever exposed to anti-TNF were compared using Cox proportional hazards models adjusted using deciles of propensity score (DP) which included baseline age, gender, DAS score, HAQ, disease duration, use of steroids, current/previous cyclophosphamide, smoking and registration date. The first 6 months of follow-up were excluded. There were too few Hodgkin lymphoma (HL) to compare rates.
Results: 84 incident lymphomas were confirmed: 20 in 3465 nbDMARD-treated subjects and 64 in 11987 anti-TNF (152 versus 96 per 100000 person-years (pyrs); Table). After adjusting using DP there was no difference in risk of lymphoma between the cohorts; hazard ratio (HR) for anti-TNF 1.13 (95% CI 0.55, 2.31). There were 5 (22%) HL in the nbDMARD cohort and 9 (13%) in anti-TNF. Among 71 NHL, the most frequent subtype was diffuse large B cell lymphoma; 8 (50% of NHL) in nbDMARD and 25 (45%) anti-TNF. There was no significant difference in risk of NHL between the cohorts (table).
Conclusion: There is no evidence that anti-TNF increases the risk of lymphoma over the background risk associated with RA, but further follow up is needed to establish if the picture changes with time.
Table
|
nbDMARD N=3465 |
Anti-TNF N=11987 |
|
|
Follow-up (pyrs) |
13186 |
66353 |
|
Median follow-up (pyrs; IQR) |
4.5 (2.6, 5.9) |
6.4 (4.8, 7.4) |
|
Age: (years) Mean (SD) |
60 (12) |
56 (12) |
|
Gender: N(%) female |
2545 (73) |
9145 (76) |
|
RA disease duration: (years) Median (IQR) |
6 (1, 15) |
11 (6, 19) |
|
DAS28 score: mean (SD) |
5.3 (1.1) |
6.6 (1.0) |
|
HAQ: mean (SD) |
1.5 (0.7) |
2.0 (0.6) |
|
Lymphoma: N |
20 |
64 |
|
Lymphoma: Rate per 100000 pyrs (95% CI) |
152 (93, 234) |
96 (74, 123) |
|
Lymphoma: Age and gender adjusted HR (95% CI) |
Referent |
0.71 (0.43, 1.20) |
|
Lymphoma: DP adjusted HR (95% CI) |
Referent |
1.13 (0.55, 2.31) |
|
Hodgkin lymphoma: N |
4 |
9 |
|
Hodgkin lymphoma: Rate per 100000 pyrs (95% CI) |
30 (8, 78) |
14 (6, 26) |
|
Non-Hodgkin lymphoma: N |
16 |
55 |
|
NHL: Rate per 100000 pyrs (95% CI) |
121 (69, 197) |
83 (62, 108) |
|
NHL: Age and gender adjusted HR (95% CI) |
Referent |
0.79 (0.44, 1.40) |
|
NHL: DP adjusted HR (95% CI) |
Referent |
1.26 (0.58, 2.72) |
Disclosure:
L. K. Mercer,
None;
M. Lunt,
None;
A. S. Low,
None;
J. B. Galloway,
None;
K. Watson,
None;
W. G. Dixon,
None;
D. P. Symmons,
None;
K. L. Hyrich,
None;
O. B. O. T. BSRBR,
BSR Biologcs Register,
2.
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