ABSTRACT: The aging process is difficult, involving multisystem functional decline, and the pharmacokinetics of medications are altered in the older population, resulting in increased risks. Concerns associated with biologic therapy are demonstrated in case reports. Analysis of the literature about biologic therapy for rheumatologic conditions in the geriatric population, such as rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, is limited by a lack of data about older subjects in clinical trials. Safety concerns in older patients include infection, hepatitis B, and infusion reaction risks. For some older patients, biologic therapy is indicated, given the lack of effectiveness of previous therapies, and it provides humane treatment. However, the threshold is much higher in this population than in adults of younger age because of the increased risks. (J Musculoskel Med. 2010;27:175-180)
Actress Bette Davis said, “Aging ain’t for sissies.” The aging process is difficult, involving multisystem functional decline in which defects in multiple homeostatic mechanisms are acquired, resulting in a markedly reduced capacity to respond to stress. Although the process is highly time-dependent and mirrors chronological age, in any given person it can be highly variable.1,2 (For more on difficulties in aging, see the Box, “Organ-specific manifestations of aging.”)
In addition, the pharmacokinetics of medications are altered in the older population, resulting in increased risks with their use. As the geriatric population continues to grow, the need for physicians to become more familiar with the special considerations related to medication use in these patients is increasing accordingly.
A number of specific concerns are associated with biologic therapy for older patients. In discussing its use in the geriatric population, several aspects must be considered before an analysis of data that describe outcomes is helpful.
In this article, I discuss the treatment of older patients who have rheumatoid arthritis (RA) and other rheumatologic conditions with biologic agents, particularly the anti–tumor necrosis factor α (anti–TNF-α) therapies. A brief description of 3 actual patients who exemplify some specific concerns will be described, followed by a discussion of the physiology of aging, as well as the effects of aging on the immune system. A review of the literature documenting the outcomes of biologic therapy in older patients with various diseases will be described.
Special concerns in the use of biologic therapy in older patients are demonstrated in the following 3 patient cases:
Case 1. An 89-year-old woman with psoriatic arthritis (PsA) was referred for further therapy. Her past medical history was notable for a lack of previous significant infections. At age 87 years, 2 years before presentation, she received methotrexate (MTX) and adalimumab for 18 months; there was some improvement of her synovitis.
The patient then was admitted to the medical ICU in acute respiratory distress. All medications were discontinued. She had a prolonged course in the ICU, requiring intubation. Her blood cultures were positive for Escherichia coli. She survived and then was referred to me. This case demonstrates life-threatening infection as a major concern when biologic agents are used in older patients.
Case 2. A 74-year-old woman with a long-standing history of severe RA who had been treated with multiple disease-modifying antirheumatic drugs (DMARDs) was referred for further therapy. Her medical history included a personal history of breast cancer in the distant past. She also had an approximately 40-pack-per-year smoking history, although she had quit smoking cigarettes 20 years before her presentation.
At age 73 years, this patient received etanercept weekly for 6 months. Before this therapy, she had a normal baseline chest x-ray film and negative purified protein derivative test results. Etanercept was discontinued after 6 months because of a lack of effectiveness and the development of a diffuse rash. Five months after etanercept was discontinued, the patient experienced weight loss, a cough, and night sweats and was referred to me for further therapy. A chest x-ray film revealed a new lung mass, the biopsy of which showed adenocarcinoma of the lung. This case demonstrates another important problem of biologic therapy in older patients, an increased risk of malignancy.
Case 3. A 74-year-old woman with severe RA and interstitial lung disease (ILD) was treated with azathioprine (AZA) for several years; her synovitis and pneumonitis were controlled. Four years earlier, she had experienced increasing shortness of breath and a new mass was seen on her chest x-ray film. Biopsy of this mass revealed a low-grade B-cell lymphoma (mucosa-associated lymphoid tissue).
The oncology department treated the patient with rituximab, 375 mg/m2 weekly for 4 weeks, then monthly for 2 years. She then received maintenance therapy with rituximab on a monthly basis; remission of the lymphoma was achieved, as well as complete remission of her rheumatoid synovitis and ILD.
After 2 years of rituximab maintenance, the patient’s treatment was discontinued. She was then referred back to the rheumatology clinic, where her synovitis continues to be in remission but her ILD has flared. Therapy with AZA has been restarted and good control of her pulmonary disease has been achieved. This case demonstrates the potential that rituximab holds for management of rheumatologic diseases in older patients.
1. Cobbs EL, Duthie EH, Murphy JB, eds. Geriatrics Review Syllabus: A Core Curriculum in Geriatric Medicine. 4th ed. New York: Kendall Hunt Publishing Company; 2001:10-21, 202, 233-240, 279-284.
2. Cassel CK, Cohen HJ, Larsen EB, et al, eds. Geriatric Medicine. 3rd ed. New York: Springer Verlag; 1997:3-4, 233-234, 357-359, 586-589, 600-622.
3. Naylor K, Li G, Vallejo AN, et al. The influence of age on T cell generation and TCR diversity. J Immunol. 2005;174:7446-7452.
4. Goronzy JJ, Fujii H, Weyand CM. Telomeres, immune aging and autoimmunity. Exp Gerontol. 2006;41:246-251.
5. Fleischmann R, Iqbal I. Risk:benefit profile of etanercept in elderly patients with rheumatoid arthritis, ankylosing spondylitis or psoriatic arthritis. Drugs Aging. 2007;24:239-254.
6. Bongartz T, Sutton AJ, Sweeting MJ, et al. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006;295:2275-2285.
7. Schneeweiss S, Setoguchi S, Weinblatt ME, et al. Anti-tumor necrosis factor alpha therapy and the risk of serious bacterial infections in elderly patients with rheumatoid arthritis. Arthritis Rheum. 2007;56:1754-1764.
8. Maillard H, Ornetti P, Grimault L, et al. Severe pyogenic infections in patients taking infliximab: a regional cohort study. Joint Bone Spine. 2005;72:330-334.
9. Takeuchi T, Tatsuki Y, Nogami Y, et al. Postmarketing surveillance of the safety profile of infliximab in 5000 Japanese patients with rheumatoid arthritis. Ann Rheum Dis. 2008;67:189-194.
10. Hoffman GS, Cid MC, Rendt-Zagar KE, et al; Infliximab-GCA Study Group. Infliximab for maintenance of glucocorticosteroid-induced remission of giant cell arteritis. Ann Intern Med. 2007;146:621-630.
11. Salvarani C, Macchioni P, Manzini C, et al. Infliximab plus prednisone or placebo plus prednisone for the initial treatment of polymyalgia rheumatica: a randomized trial. Ann Intern Med. 2007;146:631-639.
12. Catanoso MG, Macchioni P, Boiardi L, et al. Treatment of refractory polymyalgia rheumatica with etanercept: an open pilot study. Arthritis Rheum. 2007;57:1514-1519.
13. Stone JH, Holbrook JT, Marriott MA, et al; Wegener’s Granulomatosis Etanercept Trial Research Group. Solid malignancies among patients in the Wegener’s Granulomatosis Etanercept Trial. Arthritis Rheum. 2006;54:1608-1618.
14. Rennard SI, Fogarty C, Kelsen S, et al; COPD Investigators. The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007;175:926-934.
15. McLaughlin P, Grillo-López AJ, Link BK, et al. Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998;16:2825-2833.
16. Hainsworth JD, Litchy S, Burris HA 3rd, et al. Rituximab as first-line and maintenance therapy for patients with indolent non-hodgkin’s lymphoma. J Clin Oncol. 2002;20:4261-4267.