THU0174 Analysis of Non-melanoma Skin Cancer Across the Tofacitinib Rheumatoid Arthritis Clinical Programme

Abstract

BackgroundTofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA).ObjectivesThe incidence of non-melanoma skin cancer (NMSC) in the tofacitinib RA programme was evaluated using data from randomised Phase (P) 1, 2, 3 and open-label long-term extension (LTE) RA studies (P1P2P3LTE studies).MethodsNMSC data (cut-off date: 30 Aug 2013) were pooled from two P1, eight P2, six P3 and two LTE studies; LTE data collection and analyses are ongoing; study databases unlocked. Patients (pts) with RA in P1, P3 and LTE studies received tofacitinib 5 or 10 mg twice daily (BID) either as monotherapy or with background disease-modifying antirheumatic drugs (DMARDs). LTE pts were enrolled from qualifying P1, P2 and P3 studies; pts from P2 studies received tofacitinib 1 to 30 mg BID or 20 mg once daily. Incidence rates (IRs) per 100 pt-years (py) of exposure for first NMSC were calculated for combined doses (all doses) of tofacitinib in the P1P2P3LTE pt population. The overall NMSC IR was analysed as well as IRs for subgroup analyses according to the following conditions: tofacitinib dose (5 mg vs 10 mg BID); tofacitinib monotherapy vs tofacitinib + background DMARDs; prior tumour necrosis factor inhibitors (TNFi); pt age (≥65 vs <65); ethnic background; and time period.Results6092 pts (15103 py of exposure) received tofacitinib (all doses) in the P1P2P3LTE studies. ≥1 events of NMSC occurred in 83 pts receiving tofacitinib (all doses), of which squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) occurred in 39 and 52 pts, respectively. Five pts had a history of NMSC prior to tofacitinib exposure; 78 pts did not. In the P1P2P3LTE population, IRs were 0.55 (95% confidence interval [CI] 0.45, 0.69), 0.26 (0.19, 0.35) and 0.35 (0.26, 0.45) for NMSC overall, SCC and BCC, respectively. NMSC IRs for pts from the P1/2/3 and LTE cohorts receiving tofacitinib 5 mg BID were 0.61 (0.34, 1.10) and 0.41 (0.26, 0.66), respectively; for pts receiving tofacitinib 10 mg BID, NMSC IRs were 0.47 (0.24, 0.90) and 0.79 (0.60, 1.05), respectively. P1P2P3LTE pts on background DMARDs had a numerically higher IR (IR 0.64, 95% CI 0.49, 0.84) than tofacitinib monotherapy pts (IR 0.43, 95% CI 0.30, 0.64). There was a higher rate of NMSC in pts with prior TNFi (IR 1.01, 95% CI 0.67, 1.51) vs TNFi-naïve pts (IR 0.47, 95% CI 0.37, 0.61). Pts ≥65 years had a higher rate of NMSC (IR 1.67, 95% CI 1.19, 2.35) vs pts <65 years (IR 0.38, 95% CI 0.29, 0.51). Pts of White ethnicity had the highest IR of NMSC vs pts of Asian, Black or Other ethnicity (0.86 vs 0.03, 0.00 or 0.14). NMSC IRs, analysed in 6-month intervals (through >84 months), were stable over time.ConclusionsNMSC IRs appeared consistent with published estimates in pts with RA treated with TNFi (IR 0.22-0.66).1 The overall NMSC IR in the tofacitinib clinical development programme remained stable over time.ReferencesAskling J et al. Pharmacoepidemiol Drug Saf 2011;20:119-130.AcknowledgementsPreviously presented (Curtis JR et al. Arthritis Rheum 2014; 66(11): S196 ...

Safety Profile of Baricitinib in Patients with Active Rheumatoid Arthritis with over 2 Years Median Time in Treatment

“…Exposure time within baricitinib trials is relatively limited, and longer time periods will be needed to further evaluate malignancy risk. At present, the malignancy (excluding NMSC) IR appears to be similar to those reported in other RA therapeutic programs 24,25,28,44,45 and remained stable over time. The SIR of 1.04 (95% CI 0.79-1.36) indicates that the cancer IR in the baricitinib RA program is not increased compared to a similar United States population sample 21 .…”

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“…In RA trials, the risk of malignancy in tofacitinib-treated patients was not significantly increased 83 . Although tofacitinib is associated with an increased risk of nonmelanoma skin cancer, the effect size is similar to that seen with other biologic agents such as TNF inhibitors 82 . When Jakinibs have been used for transplant-rejection prophylaxis in combination with other immunosuppressive drugs, the risk of developing post-transplant lymphoproliferative disease (PTLD) is increased.…”

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“…EBV‐associated post‐transplant lymphoproliferative disorder was observed at an increased rate in renal transplant patients treated with tofacitinib, but these patients also received additional, concomitant immunosuppressive medications . So far, the RA patients treated with tofacitinib or baricitinib seem to have a similar risk of cancer to those treated with other biological therapies, although long‐term follow‐up studies are certainly missing to assess whether blockade of the JAK–STAT pathway is associated with increased risk of cancer …”

“…155 So far, the RA patients treated with tofacitinib or baricitinib seem to have a similar risk of cancer to those treated with other biological therapies, although long-term follow-up studies are certainly missing to assess whether blockade of the JAK-STAT pathway is associated with increased risk of cancer. 156,157…”