Initiation of Rheumatoid Arthritis Treatments and the Risk of Serious Infections

Overview

Journal Rheumatology (Oxford)

Publisher Oxford University Press

Specialty Rheumatology

Date 2009 Nov 13

PMID 19906833

Citations 24

Authors

Carlos G Grijalva

Lisa Kaltenbach

Patrick G Arbogast

Edward F Mitchel Jr

Marie R Griffin

Affiliations

Soon will be listed here.

Abstract

Objective: In clinical trials of RA patients on traditional DMARDs, the addition of TNF-alpha antagonists increased infections compared with addition of placebo. Our objective was to compare serious infections following initiation of different RA regimens. Prior comparative studies of DMARD initiation have yielded conflicting results.

Methods: We estimated hospitalization rates for infections following initiation of TNF-alpha antagonists, other DMARDs and oral glucocorticoids in Tennessee Medicaid-enrolled RA patients (1995-2005). Exposure time was measured using pharmacy information and infections were identified using validated definitions. Initiation of RA regimens was compared using Cox regression models with MTX as the reference. Sensitivity analyses excluded glucocorticoid users, applied a first exposure carried forward approach, restricted observations to 2002-05 and first episodes of use and explored effects of unmeasured confounders.

Results: We identified 28 906 new episodes of medication use, including TNF-alpha antagonists (8%), MTX alone (15%) and glucocorticoids alone (57%). Compared with MTX initiation, TNF-alpha antagonist initiation did not significantly increase the risk of hospitalizations for pneumonia [adjusted hazard ratio (aHR) 1.61; 95% CI 0.85, 3.03] or any infection (aHR 1.31; 95% CI 0.78, 2.19). Initiation of LEF, SSZ or HCQ did not increase serious infections, compared with MTX. Both initiation and concurrent glucocorticoid use were associated with a dose-dependent increase in serious infections. Sensitivity analyses showed consistent results.

Conclusions: Compared with initiation of MTX alone, initiation of TNF-alpha antagonists was not associated with a large increase in the risk of serious infections. Glucocorticoid use was associated with a dose-dependent increase in the risk of these infections.

Citing Articles

Risk of severe infections after the introduction of biologic DMARDs in people with newly diagnosed rheumatoid arthritis: a population-based interrupted time-series analysis.

Zhou V, Lacaille D, Lu N, Kopec J, Qian Y, Nosyk B Rheumatology (Oxford). 2023; 62(12):3858-3865.

PMID: 37014364 PMC: 10691931. DOI: 10.1093/rheumatology/kead158.

Impact of Concomitant Corticosteroids on Tofacitinib Induction Efficacy and Infection Rates in Ulcerative Colitis.

Lichtenstein G, Cohen B, Salese L, Modesto I, Wang W, Chan G Dig Dis Sci. 2023; 68(6):2624-2634.

PMID: 36739367 PMC: 9899108. DOI: 10.1007/s10620-022-07794-0.

Current Take on Systemic Sclerosis Patients' Vaccination Recommendations.

Murdaca G, Noberasco G, Olobardi D, Lunardi C, Maule M, Delfino L Vaccines (Basel). 2021; 9(12).

PMID: 34960174 PMC: 8708328. DOI: 10.3390/vaccines9121426.

Acute respiratory viral adverse events during use of antirheumatic disease therapies: A scoping review.

Kilian A, Chock Y, Huang I, Graef E, Upton L, Khilnani A Semin Arthritis Rheum. 2020; 50(5):1191-1201.

PMID: 32931985 PMC: 7832282. DOI: 10.1016/j.semarthrit.2020.07.007.

Preventing Infections by Encapsulated Bacteria Through Vaccine Prophylaxis in Inflammatory Bowel Disease.

Lenti M, Mengoli C, Vernero M, Aronico N, Conti L, Borrelli de Andreis F Front Immunol. 2020; 11:485.

PMID: 32269571 PMC: 7109446. DOI: 10.3389/fimmu.2020.00485.

References

Solomon D, Avorn J, Katz J, Weinblatt M, Setoguchi S, Levin R . Immunosuppressive medications and hospitalization for cardiovascular events in patients with rheumatoid arthritis. Arthritis Rheum. 2006; 54(12):3790-8. DOI: 10.1002/art.22255. View

Dixon W, Symmons D, Lunt M, Watson K, Hyrich K, Silman A . Serious infection following anti-tumor necrosis factor alpha therapy in patients with rheumatoid arthritis: lessons from interpreting data from observational studies. Arthritis Rheum. 2007; 56(9):2896-904. PMC: 2435418. DOI: 10.1002/art.22808. View

Weinblatt M, Kremer J, Bankhurst A, Bulpitt K, Fleischmann R, Fox R . A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med. 1999; 340(4):253-9. DOI: 10.1056/NEJM199901283400401. View

Schneeweiss S . Sensitivity analysis and external adjustment for unmeasured confounders in epidemiologic database studies of therapeutics. Pharmacoepidemiol Drug Saf. 2006; 15(5):291-303. DOI: 10.1002/pds.1200. View

Keystone E, Kavanaugh A, Sharp J, Tannenbaum H, Hua Y, Teoh L . Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy: a randomized,.... Arthritis Rheum. 2004; 50(5):1400-11. DOI: 10.1002/art.20217. View

Solomon D, Lunt M, Schneeweiss S . The risk of infection associated with tumor necrosis factor alpha antagonists: making sense of epidemiologic evidence. Arthritis Rheum. 2008; 58(4):919-28. DOI: 10.1002/art.23396. View

Schneeweiss S, Setoguchi S, Weinblatt M, Katz J, Avorn J, Sax P . Anti-tumor necrosis factor alpha therapy and the risk of serious bacterial infections in elderly patients with rheumatoid arthritis. Arthritis Rheum. 2007; 56(6):1754-64. DOI: 10.1002/art.22600. View

Listing J, Strangfeld A, Kary S, Rau R, von Hinueber U, Stoyanova-Scholz M . Infections in patients with rheumatoid arthritis treated with biologic agents. Arthritis Rheum. 2005; 52(11):3403-12. DOI: 10.1002/art.21386. View

Ray W, Griffin M . Use of Medicaid data for pharmacoepidemiology. Am J Epidemiol. 1989; 129(4):837-49. DOI: 10.1093/oxfordjournals.aje.a115198. View

10.

. Guidelines for the management of rheumatoid arthritis: 2002 Update. Arthritis Rheum. 2002; 46(2):328-46. DOI: 10.1002/art.10148. View

11.

Bijlsma J, Boers M, Saag K, Furst D . Glucocorticoids in the treatment of early and late RA. Ann Rheum Dis. 2003; 62(11):1033-7. PMC: 1754359. DOI: 10.1136/ard.62.11.1033. View

12.

Dixon W, Watson K, Lunt M, Hyrich K, Silman A, Symmons D . Rates of serious infection, including site-specific and bacterial intracellular infection, in rheumatoid arthritis patients receiving anti-tumor necrosis factor therapy: results from the British Society for Rheumatology Biologics Register. Arthritis Rheum. 2006; 54(8):2368-76. DOI: 10.1002/art.21978. View

13.

Doran M, Crowson C, Pond G, OFallon W, Gabriel S . Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum. 2002; 46(9):2287-93. DOI: 10.1002/art.10524. View

14.

Saag K, Teng G, Patkar N, Anuntiyo J, Finney C, Curtis J . American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum. 2008; 59(6):762-84. DOI: 10.1002/art.23721. View

15.

Cadarette S, Katz J, Brookhart M, Sturmer T, Stedman M, Solomon D . Relative effectiveness of osteoporosis drugs for preventing nonvertebral fracture. Ann Intern Med. 2008; 148(9):637-46. PMC: 3285566. DOI: 10.7326/0003-4819-148-9-200805060-00003. View

16.

Bongartz T, Sutton A, Sweeting M, Buchan I, Matteson E, Montori V . 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(19):2275-85. DOI: 10.1001/jama.295.19.2275. View

17.

Schneeweiss S, Robicsek A, Scranton R, Zuckerman D, Solomon D . Veteran's affairs hospital discharge databases coded serious bacterial infections accurately. J Clin Epidemiol. 2007; 60(4):397-409. DOI: 10.1016/j.jclinepi.2006.07.011. View

18.

Ting G, Schneeweiss S, Katz J, Weinblatt M, Cabral D, Scranton R . Performance of a rheumatoid arthritis records-based index of severity. J Rheumatol. 2005; 32(9):1679-87. View

19.

Donahue K, Gartlehner G, Jonas D, Lux L, Thieda P, Jonas B . Systematic review: comparative effectiveness and harms of disease-modifying medications for rheumatoid arthritis. Ann Intern Med. 2007; 148(2):124-34. DOI: 10.7326/0003-4819-148-2-200801150-00192. View

20.

Grijalva C, Chung C, Arbogast P, Stein C, Mitchel Jr E, Griffin M . Assessment of adherence to and persistence on disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis. Med Care. 2007; 45(10 Supl 2):S66-76. DOI: 10.1097/MLR.0b013e318041384c. View