Cancer risk in patients with rheumatoid arthritis treated with anti-tumor necrosis factor alpha therapies: does the risk change with the time since start of treatment?
OBJECTIVE
To determine the short-term and medium-term risks of cancer in patients receiving anti-tumor necrosis factor alpha (anti-TNFalpha) therapies that have proven effective in the treatment of chronic inflammatory conditions.


METHODS
By linking together data from the Swedish Biologics Register, Swedish registers of RA, and the Swedish Cancer Register, we identified and analyzed for cancer occurrence a national cohort of 6,366 patients with RA who first started anti-TNF therapy between January 1999 and July 2006. As comparators, we used a national biologics-naive RA cohort (n = 61,160), a cohort of RA patients newly starting methotrexate (n = 5,989), a cohort of RA patients newly starting disease-modifying antirheumatic drug combination therapy (n = 1,838), and the general population of Sweden. Relative risks (RRs) were estimated using Cox regression analyses, examining overall RR as well as RR by time since the first start of anti-TNF therapy, by the duration of active anti-TNF therapy, and by the anti-TNF agent received.


RESULTS
During 25,693 person-years of followup in 6,366 patients newly starting anti-TNF, 240 first cancers occurred, yielding an RR of 1.00 (95% confidence interval 0.86-1.15) versus the biologics-naive RA cohort, and similar RRs versus the other 2 RA comparators. RRs did not increase with increasing time since the start of anti-TNF therapy, nor with the cumulative duration of active anti-TNF therapy. During the first year following the first treatment start, but not thereafter, dissimilar cancer risks for adalimumab, etanercept, and infliximab were observed.


CONCLUSIONS
During the first 6 years after the start of anti-TNF therapy in routine care, no overall elevation of cancer risk and no increase with followup time were observed.
Askling
Johan
J
Department of Medicine Solna, Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden. johan.askling@ki.se
van Vollenhoven
Ronald F
RF
Granath
Fredrik
F
Raaschou
Pauline
P
Fored
C Michael
CM
Baecklund
Eva
E
Dackhammar
Christina
C
Feltelius
Nils
N
Cöster
Lars
L
Geborek
Pierre
P
Jacobsson
Lennart T
LT
Lindblad
Staffan
S
Rantapää-Dahlqvist
Solbritt
S
Saxne
Tore
T
Klareskog
Lars
L
D000068879:Adalimumab; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D000068800:Etanercept; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D000069285:Infliximab; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology*; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept; D008727:Methotrexate