Omalizumab and the risk of malignancy: results from a pooled analysis.

BACKGROUND: Since initial registration, the omalizumab clinical trial database has expanded considerably, with a doubling of patients exposed in the clinical trial environment. Previous pooled data (2003) from phase I to III studies of omalizumab showed a numeric imbalance in malignancies arising in omalizumab recipients (0.5%) compared with control subjects (0.2%). The previous analysis was based on limited available data, warranting further investigation. OBJECTIVE: We sought to examine the incidence of malignancy using comprehensive pooled data from clinical trials of omalizumab-treated patients. METHODS: This pooled analysis included data from 67 phase I to IV clinical trials. The prespecified primary analysis assessed the incidence of primary malignancy in 32 randomized, double-blind, placebo-controlled (RDBPC) trials. RESULTS: There were 11,459 unique patients in all clinical trials (7,789 received omalizumab). The primary analysis identified malignancies in 25 patients (RDBPC trials): 14 in 4,254 omalizumab-treated patients and 11 in 3,178 placebo-treated patients. Incidence rates per 1,000 patient-years of observation time for omalizumab- and placebo-treated patients were 4.14 (95% CI, 2.26-6.94) and 4.45 (95% CI, 2.22-7.94), respectively; the corresponding rate ratio was 0.93 (95% CI, 0.39-2.27). Primary malignancies were of varying histologic type and occurred in a number of different organ systems; no cluster of histologies was identified. CONCLUSIONS: In this pooled analysis no association was observed between omalizumab treatment and risk of malignancy in RDBPC trials; the rate ratio was below unity. The data suggest that a causal relationship between omalizumab therapy and malignancy is unlikely.

Lymphoma among patients with atopic dermatitis and/or treated with topical immunosuppressants in the United Kingdom.

BACKGROUND: Atopic dermatitis (AD) has been associated with an increased risk of lymphoma. OBJECTIVES: To assess the risk of lymphoma associated with AD and use of topical corticosteroids (TCS) or topical calcineurin inhibitors (TCI) in a database allowing medical record validation. METHODS: We conducted a nested-case control study using the United Kingdom-based The Health Improvement Network (THIN) database. We excluded patients with established risk factors for lymphoma. Cases of lymphoma were identified and classified after review of the medical records and hospital discharge files. RESULTS: In the study population of 3,500,194 individuals, we identified 2738 cases of lymphoma (1722 non-Hodgkin lymphoma [NHL], 466 Hodgkin disease, 550 indeterminate cases; overall, 188 had cutaneous involvement) and 10,949 matched controls. AD was associated with an increased lymphoma risk (odds ratio [OR], 1.83; 95% CI, 1.41-2.36). In patients with AD referred to a dermatologist, the OR further increased (OR, 3.72; 95% CI, 1.40-9.87). We did not find any cases of lymphoma in TCI users; however, the number of patients exposed to TCI was insufficient to study any possible association between lymphoma and these drugs. TCS use was associated with an increased lymphoma risk (OR, 1.46; 95% CI, 1.33-1.61). The risk increase was dependent on TCS potency (OR for high-potency TCS, 1.80; 95% CI, 1.54-2.11). The increased risk involved both Hodgkin disease and NHL, especially NHL with skin involvement (OR for high-potency TCS, 26.24; 95% CI, 13.49-51.07). CONCLUSION: Our results show an association between lymphoma-especially skin lymphoma-and use of TCS. The risk increased with duration of exposure and potency of TCS.

Topical treatments with pimecrolimus, tacrolimus and medium- to high-potency corticosteroids, and risk of lymphoma.

BACKGROUND/AIMS: A potential risk of lymphoma associated with the use of topical calcineurin inhibitors is debated. We assessed the risk of lymphoma among patients treated with topical pimecrolimus, tacrolimus or corticosteroids. METHODS: We conducted a cohort study using health insurance claims data. Cohorts of initiators of topical pimecrolimus, tacrolimus and corticosteroids, along with cohorts of persons with untreated dermatitis and randomly sampled enrollees were identified from January 2002 to June 2006. Lymphomas were identified using insurance claims and adjudicated by medical records review. We adjusted for confounders by propensity score matching. RESULTS: Among 92,585 pimecrolimus initiators contributing 121,289 person-years of follow-up, we identified 26 lymphomas yielding an incidence of 21/100,000 person-years. This incidence of lymphoma was similar to that among tacrolimus users (rate ratio, RR = 1.16; 95% confidence interval, CI = 0.74-1.82) as well as corticosteroid users (RR = 1.15; 95% CI = 0.49-2.72). All three topical treatments were associated with an increased risk of lymphoma compared with the general population (RR(Pim) = 2.89; RR(Tac) = 2.82; RR(Cort) = 2.10) suggesting increased detection of preexisting lymphomas. CONCLUSION: This study did not find an increased risk of lymphoma among initiators of topical pimecrolimus relative to other topical agents during an average follow-up of 1.3 years. Longer-term studies may be needed.

Cancer incidence in a general population of asthma patients.

PURPOSE: Several studies have assessed the association between asthma and cancer but none of them revealed a clear pattern of association. We aimed to examine the association between asthma, chronic obstructive pulmonary disease (COPD), and cancer. METHODS: We performed a cohort study with a nested case-control analysis using the General Practitioner Research Database in the UK. We defined three cohorts: patients with asthma, patients with COPD, and general population. During the follow-up, we identified a total of 5263 incident cases of cancer. We conducted a nested case-control analysis that included all cancer cases as well as 20 000 controls free of cancer frequency-matched on age, sex, and calendar year. RESULTS: Patients with asthma did not have an overall greater risk of cancer compared with the general population (odds ratio = 0.93, 95% confidence interval (CI): 0.86-1.00). However, they presented an elevated risk of experiencing lung cancer (odds ratio = 1.84, 95%CI: 1.58-2.15). Controlling for smoking and other potential confounding factors yielded a lower estimate (odds ratio = 1.35, 95%CI: 1.15-1.59). This estimate contrasted with that observed for non-smoking related cancer (0.87, 95%CI: 0.80-0.94). Overall, respiratory drugs did not seem to be associated with cancer among asthmatic patients. Patients with COPD had an Odds ratio of cancer of 1.26 (95%CI: 1.12-1.43) compared with the general population. CONCLUSIONS: Asthma was not associated with an increased risk of cancer. In fact, the risk of non-smoking related cancer was slightly reduced. However, we observed a small-elevated risk of lung cancer among asthmatic patients. Whether this result is a due to residual confounding and/or protopathic bias remains unclear. Further investigation is warranted to confirm or discard these associations.