Medication | Case-Control/Cohort Study | Metaanalysis Data | Clinical Trials Data |
---|---|---|---|
Baseline (broad inclusion of RA patients, unspecified medication) | Review of open prospective cohort of osteoarthritis (OA) and RA patients in the US National Data Bank for Rheumatic Diseases (NDB), n = 15,789 RA and 3,639 OA patients. RA vs OA, NMSC multivariate HR 1.19, 95% CI 1.01–1.4110 Swedish cohort analysis, n = 4160 RA patients treated with anti-TNF (infliximab, adalimumab, etanercept), mean 2.3 yrs followup; SCC (BCC not reported to Cancer Registry): inpatient RA cohort NMSC HR 1.66, 95% CI 1.50–1.84; MM HR 1.19, 95% CI 0.99–1.4213 | Danish hospital discharge registry, n = 20,699, average 7-yr followup, RA vs general population 1977–87, NMSC RR 1.3, 95% CI 1.1–1.443 | |
TNF-α inhibitors | Swedish cohort analysis, n = 4160 RA patients treated with anti-TNF (infliximab, adalimumab, etanercept), mean 2.3 yrs followup; SCC (BCC not reported to Cancer Registry); inpatient RA cohort SIR 1.66, 95% CI 1.5–1.84; early arthritis RA cohort SIR 0.7, 95% CI 0.2–1.6, TNF antagonist cohort SIR 3.6, 95% CI 1.8–6.5. Melanoma: inpatient RA cohort SIR 1.19, 95% CI 0.99–1.42, early arthritis RA cohort SIR 0.9, 95% CI 0.2–2.2, TNF antagonist cohort 0.3, 95% CI 0.0–0.1813 Swedish cohort analysis, n = 6604 RA patients treated with anti-TNF (infliximab, adalimumab, etanercept), median 3.6 yrs followup (BCC not reported to Cancer Registry): no increased risk of solid malignancy11 Review of open prospective cohort of patients in NDB, n = 15,789 RA and 3639 OA patients: NMSC in TNF inhibitor (infliximab, adalimumab, etanercept) without MTX, HR 1.24, 95% CI 0.97–1.58, with MTX, HR 1.97, 95% CI 1.51–2.5810 Review of NDB, n = 13,001, comparison RA patients treated with anti-TNF agents (infliximab, etanercept, adalimumab) compared with non-biologic treated RA patients: melanoma, OR 2.3, 95% CI 0.9–5.4, NMSC, OR, 1.5 95% CI 1.2–1.8; infliximab alone, NMSC, OR 1.7, 95% CI 1.3–2.214 | RA clinical trials database reviewed, n = 1442, mean etanercept exposure 3.7 yrs; no increased incidence of SCC in etanercept treated patients16 Combined RCT data of etanercept in RA, 9 trials, n = 3316. Etanercept treated n = 2244, 8 BCC, 1 SCC, 1 MM; control group n = 1072, 2BCC, 1 NMSC, 0 MM18 Combined data from 9 RCT of RA patients treated with infliximab or adalimumab, n = 5014; exposed group n = 3493: 7 BCC, 3 BCC, 0 SCC, 0 MM17 Combined data from 36 global clinical trials of RA, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, psoriasis, juvenile idiopathic arthritis, n = 19,041 patients treated with adalimumab; comparing with national Cancer Institute dataset for controls, in RA SIR for BCC 1.24, 95% CI 1.01–1.51, and SCC 1.97, 95% CI 1.34–2.8019 Combined clinical trial data of etanercept use in multiple disease indications (RA, juvenile idiopathic arthritis, PsA, ankylosing spondylitis, psoriasis), n = 13,977. Rate ratio in RA, NMSC 1.05, 95% CI 0.31–4.50 (Gottlieb AB, Giannini EH, Mease PJ, Li J, Chi E, et al. Malignancies from patients receiving etanercept across approved indications [abstract]. Ann Rheum Dis 2008; 67 Suppl II:322. | Open-label multicenter study, etanercept 25 mg twice weekly in RA, n = 549; 2 BCC, 0 SCC, 0 MM21 |
Abatacept | Abatacept multicenter trials database, n = 4134 abatacept treated patients; NMSC excluded from analysis; MM not specifically evaluated25 | Open-label, washout (prior anti-TNF therapy) study evaluating abatacept for RA (ARRIVE trial), n = 1046; NMSC excluded from analysis22 Open-label, longterm extension of ATTAIN trial, evaluating abatacept in RA, n = 317; 2-yr followup; 3 BCC, 2 SCC, 0 MM23 1-year RCT, double-blind, placebo-controlled to evaluate safety and efficacy of abatacept in RA, n = 1795; BCC and SCC most common solid malignancy, but specific rates/data not presented24 | |
Methotrexate | Retrospective review, RA patients, n = 458, average followup 9.3 yrs; melanoma, SIR 3.0, 95% CI 1.2–6.2 (control = Victorian State Cancer Registry, Australia/general population representation); NMSC not in VSCR registry12 Review of open prospective cohort of patients in the NDB, n = 15,789 RA and 3639 OA patients: NMSC in TNF inhibitor (infliximab, adalimumab, etanercept), MTX without TNF, HR 1.15, 95% CI 0.81–1.6410 | ||
Azathioprine | Prospective cohort study, a mix of RA, lupus, IBD, and other nontransplant patients treated with azathioprine (68%) or cyclophosphamide (28%), n = 1634 patients; increase in expected number of SCC and BCC vs “general population” of controls (undefined)15 | ||
Prednisone | |||
Rituximab | Clinical trials pooled safety data, 9 trials, n = 2578 (501.3 pt-yrs), NMSC excluded from study data26 |
NMSC: non-melanoma skin cancer; HR: hazard ratio; TNF: tumor necrosis factor; SCC: squamous cell carcinomas; BCC: basal cell carcinoma; MM: malignant melanoma; SIR: standardized incidence ratio; IBD: inflammatory bowel disease; RCT: randomized controlled trial.