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Risk of incident or recurrent malignancies among patients with rheumatoid arthritis exposed to biologic therapy in the German biologics register RABBIT.

Strangfeld A, Hierse F, Rau R, Burmester GR, Krummel-Lorenz B, Demary W, Listing J, Zink A - Arthritis Res. Ther. (2010)

Bottom Line: Forty-four of these patients were ever exposed to anti-TNFalpha treatment (IR = 5.1/1,000 pyrs).No significant differences in the overall incidence of malignancies in patients exposed or unexposed to anti-TNFalpha or anakinra treatment were found.However, in particular this last finding needs further validation in larger data sets.

View Article: PubMed Central - HTML - PubMed

Affiliation: German Rheumatism Research Centre Berlin, a Leibniz institute, Charitéplatz 1, 10117 Berlin, Germany. Strangfeld@drfz.de

ABSTRACT

Introduction: We used the data of the German biologics register RABBIT, a nationwide prospective cohort study, to investigate the risk of new or recurrent malignancy in patients with rheumatoid arthritis (RA) receiving biologics compared to conventional disease modifying anti-rheumatic drugs (DMARDs).

Methods: The analysis was based on patients with RA enrolled in RABBIT at the start of a biologic or conventional DMARD therapy between 01 May 2001 and 31 December 2006. Incidences of first or recurrent malignancies were analysed separately. A nested case-control design was used to investigate the risk of developing a first malignancy. Matching criteria were: age, gender, follow-up time, disease activity score based on 28 joint counts (DAS28) at study entry, smoking status, and selected chronic co-morbid conditions (obstructive or other lung disease, kidney, liver or gastrointestinal disease, psoriasis).

Results: A prior malignancy was reported in 122 out of 5,120 patients. Fifty-eight of these patients had received anti-TNFalpha agents, 9 anakinra, and 55 conventional DMARDs at study entry. In 14 patients (ever exposed to anti-TNFalpha: eight, to anakinra: one) 15 recurrent cancers were observed. The average time period since the onset of the first malignancy was nine years. Crude recurrence rates per 1,000 patient-years (pyrs) were 45.5 for patients exposed to anti-TNFalpha agents, 32.3 for anakinra patients and 31.4 for patients exposed to DMARDs only (Incidence rate ratio anti-TNFalpha vs. DMARD = 1.4, P = 0.6.). In patients without prior cancer, 74 patients (70% female, mean age: 61.3) developed a first malignancy during the observation. This corresponds to an incidence rate (IR) of 6.0/1,000 pyrs. Forty-four of these patients were ever exposed to anti-TNFalpha treatment (IR = 5.1/1,000 pyrs). In a nested case-control study comparing cancer patients to cancer-free controls, 44 of the cancer patients and 44 of the cancer-free controls were ever exposed to anti-TNFalpha agents (P = 1.0).

Conclusions: No significant differences in the overall incidence of malignancies in patients exposed or unexposed to anti-TNFalpha or anakinra treatment were found. The same applied to the risk of recurrent malignancies. However, in particular this last finding needs further validation in larger data sets.

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Flow chart of patients included in the analysis.
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Figure 1: Flow chart of patients included in the analysis.

Mentions: Between 01 May 2001 and 31 December 2006, 5,279 patients were enrolled in RABBIT. One hundred fifty-nine patients were excluded from this analysis because of missing follow-up information or missing co-morbid condition status (Figure 1). Their baseline characteristics (age, DAS28, function, co-morbidity status) were not statistically different from the remaining 5,120 patients. Those were stratified according to their prior malignancy status, and both groups were analysed separately. A total of 124 prior malignancies were found in 122 patients: 6 lymphomas (DMARDs: 2, anti-TNFα: 4), and 118 solid tumors (DMARDs: 54, anakinra: 9, anti-TNFα: 55)]. Patients with prior malignancies were significantly older (P < 0.001), had a lower functional capacity (56% of full function vs. 60% of full function) and a higher frequency of chronic gastrointestinal disease than patients without prior malignancy (Table 1). Within both strata, we found that patients receiving biologics had significantly more active disease, and were more limited in activities of daily living (FFbH). As reported previously, there were no significant differences in the clinical characteristics of patients receiving etanercept, adalimumab, or infliximab [17], whereas anakinra patients had more treatment failures with DMARDs and a lower functional capacity (FFbH) than anti-TNFα patients. Because of the differing modes of action and the differences in the clinical characteristics, separate results are provided in the following analyses for patients receiving anti-TNFα agents and patients receiving anakinra.


Risk of incident or recurrent malignancies among patients with rheumatoid arthritis exposed to biologic therapy in the German biologics register RABBIT.

Strangfeld A, Hierse F, Rau R, Burmester GR, Krummel-Lorenz B, Demary W, Listing J, Zink A - Arthritis Res. Ther. (2010)

Flow chart of patients included in the analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875631&req=5

Figure 1: Flow chart of patients included in the analysis.
Mentions: Between 01 May 2001 and 31 December 2006, 5,279 patients were enrolled in RABBIT. One hundred fifty-nine patients were excluded from this analysis because of missing follow-up information or missing co-morbid condition status (Figure 1). Their baseline characteristics (age, DAS28, function, co-morbidity status) were not statistically different from the remaining 5,120 patients. Those were stratified according to their prior malignancy status, and both groups were analysed separately. A total of 124 prior malignancies were found in 122 patients: 6 lymphomas (DMARDs: 2, anti-TNFα: 4), and 118 solid tumors (DMARDs: 54, anakinra: 9, anti-TNFα: 55)]. Patients with prior malignancies were significantly older (P < 0.001), had a lower functional capacity (56% of full function vs. 60% of full function) and a higher frequency of chronic gastrointestinal disease than patients without prior malignancy (Table 1). Within both strata, we found that patients receiving biologics had significantly more active disease, and were more limited in activities of daily living (FFbH). As reported previously, there were no significant differences in the clinical characteristics of patients receiving etanercept, adalimumab, or infliximab [17], whereas anakinra patients had more treatment failures with DMARDs and a lower functional capacity (FFbH) than anti-TNFα patients. Because of the differing modes of action and the differences in the clinical characteristics, separate results are provided in the following analyses for patients receiving anti-TNFα agents and patients receiving anakinra.

Bottom Line: Forty-four of these patients were ever exposed to anti-TNFalpha treatment (IR = 5.1/1,000 pyrs).No significant differences in the overall incidence of malignancies in patients exposed or unexposed to anti-TNFalpha or anakinra treatment were found.However, in particular this last finding needs further validation in larger data sets.

View Article: PubMed Central - HTML - PubMed

Affiliation: German Rheumatism Research Centre Berlin, a Leibniz institute, Charitéplatz 1, 10117 Berlin, Germany. Strangfeld@drfz.de

ABSTRACT

Introduction: We used the data of the German biologics register RABBIT, a nationwide prospective cohort study, to investigate the risk of new or recurrent malignancy in patients with rheumatoid arthritis (RA) receiving biologics compared to conventional disease modifying anti-rheumatic drugs (DMARDs).

Methods: The analysis was based on patients with RA enrolled in RABBIT at the start of a biologic or conventional DMARD therapy between 01 May 2001 and 31 December 2006. Incidences of first or recurrent malignancies were analysed separately. A nested case-control design was used to investigate the risk of developing a first malignancy. Matching criteria were: age, gender, follow-up time, disease activity score based on 28 joint counts (DAS28) at study entry, smoking status, and selected chronic co-morbid conditions (obstructive or other lung disease, kidney, liver or gastrointestinal disease, psoriasis).

Results: A prior malignancy was reported in 122 out of 5,120 patients. Fifty-eight of these patients had received anti-TNFalpha agents, 9 anakinra, and 55 conventional DMARDs at study entry. In 14 patients (ever exposed to anti-TNFalpha: eight, to anakinra: one) 15 recurrent cancers were observed. The average time period since the onset of the first malignancy was nine years. Crude recurrence rates per 1,000 patient-years (pyrs) were 45.5 for patients exposed to anti-TNFalpha agents, 32.3 for anakinra patients and 31.4 for patients exposed to DMARDs only (Incidence rate ratio anti-TNFalpha vs. DMARD = 1.4, P = 0.6.). In patients without prior cancer, 74 patients (70% female, mean age: 61.3) developed a first malignancy during the observation. This corresponds to an incidence rate (IR) of 6.0/1,000 pyrs. Forty-four of these patients were ever exposed to anti-TNFalpha treatment (IR = 5.1/1,000 pyrs). In a nested case-control study comparing cancer patients to cancer-free controls, 44 of the cancer patients and 44 of the cancer-free controls were ever exposed to anti-TNFalpha agents (P = 1.0).

Conclusions: No significant differences in the overall incidence of malignancies in patients exposed or unexposed to anti-TNFalpha or anakinra treatment were found. The same applied to the risk of recurrent malignancies. However, in particular this last finding needs further validation in larger data sets.

Show MeSH
Related in: MedlinePlus