P Geborek

Haematopoietic malignancies in rheumatoid arthritis: lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists

Background: Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, and maybe also of leukaemia and multiple myeloma. The effect of tumour necrosis factor (TNF) antagonists on lymphoma risk and characteristics is unclear. Objective: To assess expected rates and relative risks of haematopoietic malignancies, especially those associated with TNF antagonists, in large population based cohorts of patients with RA. Methods: A population based cohort study was performed of patients with RA (one prevalent cohort (n = 53 067), one incident cohort (n = 3703), and one TNF antagonist treated cohort 1999 through 2003 (n = 4160)), who were linked with the Swedish Cancer Register. Additionally, the lymphoma specimens for the 12 lymphomas occurring in patients with RA exposed to TNF antagonists in Sweden 1999 through 2004 were reviewed. Results: Study of almost 500 observed haematopoietic malignancies showed that prevalent and incident patients with RA were at increased risk of lymphoma (SIR = 1.9 and 2.0, respectively) and leukaemia (SIR = 2.1 and 2.2, respectively) but not of myeloma. Patients with RA treated with TNF antagonists had a tripled lymphoma risk (SIR = 2.9) compared with the general population. After adjustment for sex, age, and disease duration, the lymphoma risk after exposure to TNF antagonists was no higher than in the other RA cohorts. Lymphomas associated with TNF antagonists had characteristics similar to those of other RA lymphomas. Conclusion: Overall, patients with RA are at equally increased risks for lymphomas and leukaemias. Patients with RA treated with TNF antagonists did not have higher lymphoma risks than other patients with RA. Prolonged observation is needed to determine the long term effects of TNF antagonists on lymphoma risk.

Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists

Background: Existing studies of solid cancers in rheumatoid arthritis (RA) reflect cancer morbidity up until the early 1990s in prevalent cohorts admitted to hospital during the 1980s. Objective: To depict the cancer pattern of contemporary patients with RA, from updated risk data from prevalent and incident RA populations. To understand the risk of solid cancer after tumour necrosis factor (TNF) treatment by obtaining cancer data from cohorts treated in routine care rather than trials. Methods: A population based study of three RA cohorts (one prevalent, admitted to hospital 1990–2003 (n = 53 067), one incident, diagnosed 1995–2003 (n = 3703), and one treated with TNF antagonists 1999–2003 (n = 4160)), which were linked with Swedish nationwide cancer and census registers and followed up for cancer occurrence through 2003. Results: With 3379 observed cancers, the prevalent RA cohort was at marginally increased overall risk of solid cancer, with 20–50% increased risks for smoke related cancers and +70% increased risk for non-melanoma skin cancer, but decreased risk for breast (−20%) and colorectal cancer (−25%). With 138 cancers, the incident RA cohort displayed a similar cancer pattern apart from non-decreased risks for colorectal cancer. TNF antagonist treated patients displayed solid cancer (n = 67) risks largely similar to those of other patients with RA. Conclusion: The cancer pattern in patients treated with TNF antagonists mirrors those of other contemporary as well as historic RA cohorts. The consistent increase in smoking associated cancers in patients with RA emphasises the potential for smoking cessation as a cancer preventive measure in RA.

Anti-tumour necrosis factor therapy in rheumatoid arthritis and risk of malignant lymphomas: relative risks and time trends in the Swedish Biologics Register

Background: Tumour necrosis factor (TNF) antagonists have proved effective as treatment against rheumatoid arthritis (RA), but the unresolved issue of whether the use of anti-TNF therapy increases the already elevated risk of lymphoma in RA remains a concern. Methods: Using the Swedish Biologics Register (ARTIS), the Swedish Cancer Register, pre-existing RA cohorts and cross-linkage with other national health and census registers, a national RA cohort (n  =  67 743) was assembled and patients who started anti-TNF therapy between 1998 and July 2006 (n  =  6604) were identified. A general population comparator (n  =  471 024) was also assembled and the incidence of lymphomas from 1999 to 31 December 2006 was assessed and compared in these individuals. Results: Among the 6604 anti-TNF-treated RA patients, 26 malignant lymphomas were observed during 26 981 person-years of follow-up, which corresponded to a relative risk (RR) of 1.35 (95% CI 0.82 to 2.11) versus anti-TNF-naive RA patients (336 lymphomas during 365 026 person-years) and 2.72 (95% CI 1.82 to 4.08) versus the general population comparator (1568 lymphomas during 3 355 849 person-years). RA patients starting anti-TNF therapy in 1998–2001 accounted for the entire increase in lymphoma risk versus the two comparators. By contrast, RR did not vary significantly by time since start of first treatment or with the accumulated duration of treatment, nor with the type of anti-TNF agent. Conclusion: Overall and as used in routine care against RA, TNF antagonists are not associated with any major further increase in the already elevated lymphoma occurrence in RA. Changes in the selection of patients for treatment may influence the observed risk.

Ten years with biologics: to whom do data on effectiveness and safety apply?

OBJECTIVES During the past decade, the position of biologics in the therapeutic armamentarium, the number of approved indications and the number of available biologics have changed. Available data on (long-term) safety might thus pertain to patient populations not comparable with contemporary patients. The aim of this study was to assess the extent to which contemporary patients who start or switch biologic therapies are comparable with those patients who gave rise to the currently available data on effectiveness and safety. METHODS We identified all adult patients with RA (n=9612), PsA (n=1417) and other SpA (n=1652) initiating a first biologic therapy between 1 January 1999 and 31 December 2008, registered in the Swedish Biologics Register (ARTIS), including information on demographics, disease characteristics and 1-year risk of first-line treatment discontinuation. RESULTS Over calendar time, measures of disease activity at start declined substantially for all indications, and diminished between first-, second- and third-line therapy starts. One-year risks of first-line therapy discontinuation increased. Switchers to anti-TNF and non-TNF biologics had different comorbidities. Despite <50% drug retention at 5 years, most patients remained exposed to some biologic. CONCLUSIONS The trends in baseline characteristics and drug retention underscores that any effects of biologics, including comparison between different biologics, must be interpreted in light of the characteristics of the population treated. The observed differences further call for continued vigilance to properly evaluate the safety profiles of biologic treatments as they are currently used. Exposure to multiple biologics presents a challenge for attribution of long-term effects.

OP0189 Long term work disability in anti-TNF therapy treated patients with psoriatic arthritis: A population-based cohort study

Background Reduced work ability leading to sick leave is a common consequence of psoriatic arthritis (PsA). TNF-antagonist therapy has been a major advance in treating several aspects of PsA. Little is known about the impact of TNF treatment on long term work disability in PsA. Objectives To study proportions of long term sick leave and disability pension before and after TNF-antagonist therapy in PsA patients. Methods Using the population-based South Swedish Arthritis Treatment Group register, we identified 191 PsA patients (median age 43years, range 18-58y, 55% men), who between Jan 2003 and Dec 2007 (allowing for a complete 4 year follow-up period) started treatment with adalimumab, etanercept, or infliximab. We linked data to the payment register by the Swedish Social Insurance Agency and calculated the proportion on any sick leave in 30-day-intervals from 12 months before treatment start until 3 years after. For each PsA patient we randomly selected 4 reference subjects from the general population matched for age, sex, area of residence, and date of inclusion. Results At treatment initiation 67% of the PsA patients were either on sick leave or received disability pension of any degree from part time thru full time. During the first 12 months after treatment start this fraction dropped to 58%, and remained at 57% after 3 years (p<0.001). Comparing PsA patients to the general population, the relative risk of being work disabled at treatment start, 12 months, and 3 years after treatment start was 4.2 (95% CI 3.4, 5.1), 3.7 (3.0, 4.5), and 3.4 (2.7, 4.2), respectively. Patients withdrawing from therapy during the follow-up period compared to patients sustaining treatment had the same baseline risk of being work disabled (69 vs 64%), but a 50% increased risk after the 3 year observational period (73 vs 53%; relative risk 1.5 [95% CI] 1.2, 1.8 for comparison between withdrawers to sustainers). Conclusions There is a decline in work disability during the first 12 months after initiation of TNF-antagonist treatment in PsA patients not explained by societal factors or secular trends. This decline was sustained for the following 3 years. Patients withdrawing from therapy have a 50% increased risk of being work disabled than patients remaining on therapy. Disclosure of Interest L. Kristensen Consultant for: Abbott, BMS, Pfizer, MSD, Mundipharma, M. Englund: None Declared, P. Geborek: None Declared, M. Neovius: None Declared, J. Askling: None Declared, L. Jacobsson Consultant for: Abbott, BMS, Pfizer, MSD, I. Petersson Consultant for: Abbott, Pfizer, MSD