Table 44Infection in patients with rheumatoid arthritis treated with oral DMARDs

StudyStudy Design
Study PopulationDrugResultsQuality Rating
*Bernatsky et al., 2007218Nested case-control
Up to 23 years
RA pts registered in claims databases in QuebecOral DMARDs including: MTX, LEF, HCQ, SSZRelative risk for infections requiring hospitalization: MTX 1.10 (95% CI, 0.98 to 1.23); all other DMARDs (includes LEF, SSZ) 0.99 (95% CI, 0.84 to 1.16); Antimalarial (includes HCQ) 1.06 (95% CI, 0.92 to 1.22)Fair
*Brassard et al., 2009238Retrospective cohort study
1980–2003 for cohort and 1992–2003 for TB incidence rates
RA pts from QuebecTraditional DMARDs including MTX and LEF, corticosteroidsRate ratio of TB associated with any DMARD use: 3.0 (95% CI, 1.6 to 5.8).Fair
*Brassard et al., 2006219Retrospective cohort study
Up to 5 years
RA pts from the PharMetrics Patient-Centric databaseSeveral oral DMARDs, biologic DMARDs, corticosteroidsAdjusted rate ratio of developing TB with use of traditional DMARDs: 1.2 (95% CI, 1.0 to 1.5).Fair
Cannon et al., 2004229Retrospective cohort
2 years (claims database)
RA ptsLEF, MTX, other DMARDRespiratory infection: LEF 20/1,000 PY, MTX 38.9/1,000 PY, Other 36.9/1,000 PYFair
Doran et al., 2002220Retrospective cohort
39 years
RA ptsSeveral oral DMARDs, corticosteroidsCompared with oral DMARDs, corticosteroids increased risk of hospitalized infection (HR, 1.56; 95% CI, 1.20 to 2.04)Fair
*Greenberg et al., 2010226
Prospective cohort
15,047 patient years
Pts with RA enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) registryMTX, oral DMARDs, anti-TNF agents, PREDAdjusted incidence rate ratio (IRR) for infections: MTX (IRR, 1.30; 95% CI, 1.12 to 1.50, P<0.001)
Adjusted incidence rate ratio (IRR) for opportunistic infections: MTX (IRR, 0.93; 95% CI, 0.54 to 1.60, P=0.781)
*Grijalva et al., 2010240Prospective cohort
3 years
Tennesee Medicaid-enrolled RA pts initiating DMARD useMTX, LEF, SSZ, HCQ, biologic DMARDs, glucocorticoidsCompared with MTX; LEF, SSZ or HCQ did not increase risks of hospitalizations due to pneumonia or serious infectionsGood
*Lacaille et al., 2008221Retrospective cohort
162,720 person years
Pts with RA from British Columbia, CanadaOral DMARDs, corticosteroidsAdjusted rate ratio for serious infections: DMARDs+corticosteroids: 1.63 (95% CI, 1.5 to 1.77); DMARDs alone: 0.92 (95% CI, 0.85 to 1.0)Fair
*McDonald et al., 2009239Retrospective cohort
7 years
Pts with RA in the Veterans Affairs health care systemTraditional DMARDsNo increased risk of infection with oral DMARDs; SSZ associated with a lower risk of herpes zoster infection (HR, 0.44; 95% CI, 0.21 to 0.91)Fair
*Smitten et al., 2008223Retrospective cohort
26.6 months
Pts with RA from U.S. PharMetrics dataMTX, LEF, HCQ, SSZMTX and HCQ decreased risk of hospitalized infection (RR, 0.81; 95% CI, 0.70 to 0.93; RR, 0.74; 95% CI, 0.62 to 0.89; respectively).Good
*Smitten et al., 2007224Retrospective cohort
12,272 (PM)38,621 (GPRD)
12.3 to 38.8 months
Pts with RA the PM database and UK GPRDCorticosteroids, traditional DMARDs, biologic DMARDsRisk of herpes zoster infection with traditional DMARDs alone (PM: OR,1.37; 95% CI, 1.18 to 1.59; GPRD, 1.27; 95% CI, 1.10 to 1.48)Fair
Wolfe et al., 2006237Prospective cohort
3.5 years
RA diagnosisPRED, LEF, SSZ, MTX, ETA, INF, ADARisk for hospitalization for pneumonia: PRED HR, 1.7 (95% CI, 1.5 to 2.1), LEF HR, 1.3 (95% CI, 1.0 to 1.5). No significant differences for SSZ, MTXFair

New study added since last review.

ADA = adalimumab; AERS = adverse events reporting system; CI = confidence interval; DMARD = disease-modifying antirheumatic drug; ETA = etanercept; GI = gastrointestinal; GPRD = General Practict Research Database; HCQ = hydroxychloroquine; HR = hazard ratio; INF = infliximab; LEF = leflunomide; MTX = methotrexate; N/A = not applicable; NR = not reported; OR = odds ratio; PM = PharMetrics; PNL = prednisolone; PRED = prednisone; Pts = patients; PY = person years; RA = rheumatoid arthritis; RR = rate ratio; SSZ = sulfasalazine; TB = tuberculosis

New study added since last review.

From: Results

Cover of Drug Therapy for Rheumatoid Arthritis in Adults: An Update
Drug Therapy for Rheumatoid Arthritis in Adults: An Update [Internet].
Comparative Effectiveness Reviews, No. 55.
Donahue KE, Jonas DE, Hansen RA, et al.

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