HIGH INCIDENCE OF SERIOUS ADVERSE EVENTS AMONG ELDERLY RHEUMATOID PATIENTS RECEIVING MONOCLONAL ANTIBODIES ANTI-TNFALPHA

Objectives: Approximately 10-33% of patients with rheumatoid arthritis (RA) are diagnosed after the age of 60. Treatment with anti-TNFalpha drugs in elderly might enhance the incidence of serious adverse events, particularly infections and cardiovascular disease. We retrospectively evaluated the safety of anti-TNFalpha therapy in elderly (age ≥ 65 yrs) and younger adult subjects (age < 65 yrs) with rheumatoid arthritis followed by a tertiary Rheumatology institution. Methods: Data regarding the safety of anti-TNFalpha therapy (infliximab, etanercept, adalimumab) in 73 elderly rheumatoid arthritis patients were retrospectively evaluated and compared with those of 236 younger patients. All patients received anti-TNFalpha at the recommended dose. Safety and survival of anti-TNFalpha drugs were assessed at regularly scheduled visit. Differences between groups were analyzed by means of a chi-square test. P < 0.05 was taken as statistically significant. Results: 1) Infliximab group. 19 pts (12 F/7 M, mean age 69,1±3,4, mean duration of disease 125,1±63,4 months) were ≥ 65 and 82 (64 F/18 M, mean age 50,1±9, mean duration of disease 139,4±81,3 months) were < 65 years of age. All patients received infliximab infusion at starting dose of 3 mg/kg along with a concomitant DMARD (methotrexate or leflunomide) and low-dose prednisone (5 mg/day). The infliximab dosage could be increased to 5 mg/kg or treatment interval shortened in case of inefficay. During the follow-up (median = 27,5 months), serious adverse events occurred in 68.4% (13/19) of pts ≥ 65 as opposed to 39% (32/82) of younger pts (p = 0,03). The rate of infliximab withdrawal due to serious adverse event was higher among elderly pts (57.8% vs 29.2%, p = 0,03). Among pts ≥ 65 yrs, cardiovascular disease (35.7%) resulted the main adverse events followed by infusion reaction (28.5%) and infections (21.4%). 2) Etanercept group. 29 pts (23 F/6 M, mean age 69,6±4,1, mean duration of disease 148,1±84,6 months) were ≥ 65 and 94 (78 F/16 M, mean age 48,1±11,8, mean duration of disease 105±81,8 months) were < 65 years of age. Concomitant DMARD therapy was similar between elderly and younger subjects (68.9% and 73.4%, p = ns). During the follow-up (median = 20,5 months), the rate of withdrawal due to serious adverse events did not differ between elderly and younger pts (10.3% vs 9.5%, p = ns). Furthermore, the rate of serious infection tended to be higher in younger than elderly pts (61.9% vs 20%, p = ns). 3) Adalimumab group. 25 pts (21 F/4 M, mean age 69,1±3,3, mean duration of disease 122,8±133 months) were ≥ 65 and 60 (51 F/9 M, mean age 48,1±11,1, mean duration of disease 105±84,9 months) were < 65 years of age. 88% in elderly group took a concomitant DMARD as opposed to 71.6% in younger subject (p = ns). During the follow-up (median = 12,1 months), more pts ≥ 65 yrs developed serious adverse than younger (48% vs 25%, p = 0,01). The rate of withdrawal due to serious adverse events was higher among elderly pts (36% vs 15%, p = 0,06). Infections (40%) and solid tumors (20%) were the main types of adverse events in elderly pts. Conclusion: Among TNFalpha antagonists, only etanercept has a similar safety profile both in younger and elderly people with rheumatoid arthritis. On the basis of our observations monoclonal antibodies should be given with more caution in this population.