- Location
- Northern California, USA
As with all scientific studies, this one is subject to assumptions and estimates that may be flawed. This article attempts to review all the evidence regarding the risk of lymphoma through 2011. This requires the review and integration of a very, very large body of research. So view the results with some caution. Most of the research that was analyzed are based on adults, not children. The article has an extensive discussion of possible confounding factors which you may want to read or at least skim to help you understand the possible flaws in these results.
I have bolded the information that I thought was of greatest interest to people on the board based on recent discussions.
IXB = remicade; adalimumbad = Humira; AZA = azathioprine/6-MP/imuran; MTX = methotrexate
I have posted this article in the research section as well. It is 45 pages long.
http://cdn.intechopen.com/pdfs-wm/35455.pdf
Evaluating Lymphoma Risk in IBD
I have bolded the information that I thought was of greatest interest to people on the board based on recent discussions.
IXB = remicade; adalimumbad = Humira; AZA = azathioprine/6-MP/imuran; MTX = methotrexate
I have posted this article in the research section as well. It is 45 pages long.
http://cdn.intechopen.com/pdfs-wm/35455.pdf
Evaluating Lymphoma Risk in IBD
This systematic review and the meta-analyses carried out in this chapter have made some key findings:
There is only a small (if any) increased overall risk of lymphoma in IBD patients.
Thiopurine therapy results in a 3 to 4-fold increased risk of lymphoma in IBD patients.
The risk of lymphoma with methotrexate therapy cannot be evaluated adequately but appears to be low.
Treatment with anti-TNF drugs appears to confer an increased risk of lymphoma in IBD patients. However, this may reflect previous or concurrent immunomodulator exposure rather than the risk of anti-TNFs alone.
HSTCL is associated with long term thiopurine therapy. Additionally, anti-TNF therapy may increase this risk.
...Due to the significant morbidity associated with IBD, simply avoiding these drugs is frequently not an option. It is mandatory to provide clear communication of risks and benefits and to individualise this to the patient because lymphoma risk in IBD patients is not uniform nor is the risk of complicated disease. A recent study found that patients were more likely to tolerate the risk of adverse events due to IBD drug therapy for moderately symptomatic Crohn’s disease than gastroenterologists would choose for their patients (Johnson et al., 2010).
Patient selection is paramount. The risk of most forms of lymphoma appears to be higher in males and in older age groups. HSTCL is particularly relevant to men under the age of 35 years. Special consideration of the risks must be made in these groups...
There is ample evidence that immunomodulators and anti-TNF drugs are very effective for the treatment of IBD. In a 30 year review, Fraser et al found that there were 64% and 87% remission rates at 6 months for patients treated with AZA for Crohn’s disease and ulcerative colitis respectively (Fraser et al., 2002). Feagan et al found 65% remission at 40 weeks with MTX for Crohn’s disease (Feagan et al., 2000). In the SONIC study, there was 57% remission at 1 year for combined AZA and IXB therapy (Colombel et al., 2010). The CHARM study and its open label extension, ADHERE, for adalimumab in Crohn’s disease found improved fistula healing rates, 57% decreased hospitalisation and improved Work Productivity Scores (Panaccione et al., 2010). A Markov model found that the benefits of azathioprine for thetreatment of Crohn’s disease outweighed the risk of lymphoma but such calculations are inherently based on estimations and assumptions (Lewis et al., 2000).
Additionally, there is evidence that stopping these drugs may be harmful to patients. Azathioprine withdrawal leads to relapse within 18 months at 21% vs 8% (p=0.02, NNH=8) (Lemann et al., 2005). Methotrexate withdrawal leads to relapse within 40 weeks in 61% vs 35% (p=0.04, NNH=4) (Feagan et al., 2000). Infliximab withdrawal leads to hospitalisation within 1 year in 38% vs 23% (p=0.05, NNH=7) (Rutgeerts et al., 2004). However, the CESAME study did suggest that stopping immunomodulator therapy did return the risk of lymphoma back to baseline.
No form of screening is able to predict lymphoma development. Although, the role of vitamin D status and TPMT expression on lymphoma risk is intriguing, there is insufficient evidence to recommend the routine testing of these parameters to guide patient management.
There is only a small (if any) increased overall risk of lymphoma in IBD patients.
Thiopurine therapy results in a 3 to 4-fold increased risk of lymphoma in IBD patients.
The risk of lymphoma with methotrexate therapy cannot be evaluated adequately but appears to be low.
Treatment with anti-TNF drugs appears to confer an increased risk of lymphoma in IBD patients. However, this may reflect previous or concurrent immunomodulator exposure rather than the risk of anti-TNFs alone.
HSTCL is associated with long term thiopurine therapy. Additionally, anti-TNF therapy may increase this risk.
...Due to the significant morbidity associated with IBD, simply avoiding these drugs is frequently not an option. It is mandatory to provide clear communication of risks and benefits and to individualise this to the patient because lymphoma risk in IBD patients is not uniform nor is the risk of complicated disease. A recent study found that patients were more likely to tolerate the risk of adverse events due to IBD drug therapy for moderately symptomatic Crohn’s disease than gastroenterologists would choose for their patients (Johnson et al., 2010).
Patient selection is paramount. The risk of most forms of lymphoma appears to be higher in males and in older age groups. HSTCL is particularly relevant to men under the age of 35 years. Special consideration of the risks must be made in these groups...
There is ample evidence that immunomodulators and anti-TNF drugs are very effective for the treatment of IBD. In a 30 year review, Fraser et al found that there were 64% and 87% remission rates at 6 months for patients treated with AZA for Crohn’s disease and ulcerative colitis respectively (Fraser et al., 2002). Feagan et al found 65% remission at 40 weeks with MTX for Crohn’s disease (Feagan et al., 2000). In the SONIC study, there was 57% remission at 1 year for combined AZA and IXB therapy (Colombel et al., 2010). The CHARM study and its open label extension, ADHERE, for adalimumab in Crohn’s disease found improved fistula healing rates, 57% decreased hospitalisation and improved Work Productivity Scores (Panaccione et al., 2010). A Markov model found that the benefits of azathioprine for thetreatment of Crohn’s disease outweighed the risk of lymphoma but such calculations are inherently based on estimations and assumptions (Lewis et al., 2000).
Additionally, there is evidence that stopping these drugs may be harmful to patients. Azathioprine withdrawal leads to relapse within 18 months at 21% vs 8% (p=0.02, NNH=8) (Lemann et al., 2005). Methotrexate withdrawal leads to relapse within 40 weeks in 61% vs 35% (p=0.04, NNH=4) (Feagan et al., 2000). Infliximab withdrawal leads to hospitalisation within 1 year in 38% vs 23% (p=0.05, NNH=7) (Rutgeerts et al., 2004). However, the CESAME study did suggest that stopping immunomodulator therapy did return the risk of lymphoma back to baseline.
No form of screening is able to predict lymphoma development. Although, the role of vitamin D status and TPMT expression on lymphoma risk is intriguing, there is insufficient evidence to recommend the routine testing of these parameters to guide patient management.