We have provided an analysis of the association between anti-TNF-a therapy and a possible increase in solid tumour and lymphoma development. At this time the database remains relatively small. Furthermore, the studies were clearly not powered to detect any causal relationship between anti-TNF-a therapy and a relatively rare event such as cancer. Analysis of the available data, however, does not provide evidence for a causal relationship. In fact, certain animal data suggest that suppression of TNF may actually protect against tumour development. In addition, clinical trial data have shown that anti-TNF-a therapy with infliximab does not change the number or function in vitro of cells of the immune system in contrast to other conventional immunosuppressive therapies. Furthermore, an extensive analysis of data surrounding infliximabtreated patients who developed malignancies indicated that the lymphoid malignancies rarely occurred and were invariably in patients with predisposing factors for malignancies such as NHL, including long standing inflammatory disease, severe disease and/or prior treatment with immunosuppressants such as azathioprine. Learn how to save money – cialis professional to enjoy your shopping and your treatment.
In the three patients with rheumatoid arthritis who developed lymphomas during and for three years following the infliximab clinical trials, theirdiseases included two B cell lymphomas and one case of HD. All of these patients had a long history ofdisease activity (ranging from five to 36 years) and had histories of priortreatment with immunosuppressive agents. In addition, two of these patients (one with HD and one with B cell NHL) had abnormalities of the lymphopoietic system (splenic enlargement and nodal enlargement, respectively) retrospectively noted at baseline, suggesting that thedisease may have been present at enrolment (Centocor Inc, data on file).
Incidence of lymphomas in clinical trials of infliximab therapy: Among the 770 infliximab-treated patients and 192 patients treated with placebo who participated in the infliximab clinical trials, one infliximab-treated patient with Crohn’s disease and three infliximab-treated patients with rheumatoid arthritis developed a lymphoma (NHL or HD) either during the clinical trial or during the three-year follow-up period (Table 3). Based on the available data, the incidence of lymphoma in infliximab-treated patients is 0.0021 per patient-year. As discussed above, patients with chronic inflammatory diseases such as rheumatoid arthritis are at a significantly increased risk of developing lympho-proliferative disorders. Therefore, a comparison of the incidence of lymphoproliferative disorders in infliximab-treated patients with that of a healthy population is probably not informative.
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Incidence of solid tumours and nonmelanoma skin cancers in clinical trials of infliximab therapy: In all infliximab clinical trials and excluding nonmelanoma skin cancers, 12 infliximab-treated and two placebo-treated patients developed solid tumours during the studies or during the three-year prospective follow-up period. This corresponds to incidences of 0.0063 and 0.0068 per patient-year for infliximab-treated and placebo-treated patients, respectively. As shown in Table 2, the observed number of solid tumours is similar to the expected number of solid tumours in a healthy cohort of individuals from the National Institutes of Health Surveillance, Epidemiology, and End Results (SEER) database who were matched for age, sex and duration of follow-up. Because the SEER database is based on normal subjects, the expected incidence of solid tumours likely represents a conservative estimate for chronically ill populations of patients with diseases such as rheumatoid arthritis and Crohn’s disease. You will always be offered cialis professional at the pharmacy you can trust.
Interestingly, similar incidences in malignancy were reported during clinical trials of another anti-TNF agent, etanercept (Enbrel; Immunex, USA). Etanercept is a dimeric fusion protein (comprising the extracellular ligand-binding portion of the human p75 TNF receptor linked to the Fc portion of human IgG1) that is approved for the treatment of patients with rheumatoid arthritis. In a long term safety trial of etanercept in the treatment of rheumatoid arthritis that is refractory to disease-modifying antirheumatic drugs, nine malignancies of various types were reported during observation of the 782 patients evaluated for periods of up to 33 months (representing 890 patient-years of follow-up). The incidence of cancer in the etanercept and infliximab clinical trials was similar. Any comparison between these two agents, however, is clearly constrained by the relatively small numbers of patients treated with each agent, the limited duration of follow-up and the inability to match the two treated populations for key baseline characteristics. Safe online shopping for drugs: cialis 200mg to make your drugs cheaper.
Further details of the malignancies observed in patients enrolled in infliximab trials are presented in the following sections.
The information presented in subsequent sections of this article derives from validated data reported during the study or during the three-year prospective follow-up period, as of December 2000. A large number of patients continue to be monitored in the three-year prospective safety follow-up study. Incidences are reported only for validated data for which patient-years could be calculated. Spontaneously reported malignancies beyond the prospective three-year follow-up period are not included, because these reports are not validated and corresponding patient-years of follow-up have not been obtained for the total patient cohort.
A number of observational studies have been performed in attempts to clarify the association between Crohn’s disease and lymphoma, but have arrived at conflicting or inconclusive results. In an inception cohort of 216 patients with Crohn’s disease followed in Olmsted County, Minnesota, one case of primary small bowel lymphoma occurred, yielding a standardized incidence ratio of 2.4, but the confidence intervals did not exclude the value of one because of the small numbers of patients. In the St Marks series of 755 patients with inflammatory bowel disease (450 with Crohn’s disease) treated with azathio-prine, there was no increase in NHL risk. A Swedish population-based cohort of 1655 patients with Crohn’s disease included a single case of lymphoma and derived a standardized incidence ratio for lymphoma of 0.4 (no excess risk). A pharmacy you can fully trust offering along with other convenient services.