Table 49Overall tolerability: discontinuation data not otherwise covered by quantitative analyses

StudyStudy Design
N
Duration
Study PopulationDrugResultsQuality Rating
*Alonoso-Ruiz et al. 2008126Systematic review and meta-analysis
13 trials
7,087 patients
At least 6 months
Pts with RAADA ETA, INFRelative risk of withdrawal due to adverse event compared with control group: ADA (RR, 1.4; 95% CI, 1.0 to 2.0); ETA (RR, 0.7; 95% CI, 0.5 to 0.9); INF (RR, 2.0; 95% CI, 1.3 to 3.1)Good
*Duclos et al., 2006248Retrospective cohort
770
7 years
Pts with inflammatory rheumatism (mostly RA) that received an anti-TNF agentADA, ETA, INFTrend towards better tolerability with ETA and ADA compared with INF (P=0.06)Fair
Flendrie et al., 2003247Retrospective cohort study
230
NR
Pts with RA initiating therapy with biologic DMARDsADA, ETA, INFNo significant differences in discontinuation rates among anti-TNF drugsFair
*Hetland et al., 201073
DANBIO
Prospective cohort
2,326
48 months
Pts with RA initiating therapy with biologic DMARDsADA, ETA, INFHazard ratio for drug withdrawal: INF vs. ETA HR 1.98 (95% CI, 1.63 to 2.40); INF vs. ADA 1.35 (95% CI, 1.15 to 1.58); ADA vs. ETA 1.47 (95% CI, 1.20 to 1.80)Fair
*Hjardem et al., 2007249Retrospective cohort
235
Varied
RA pts who had received 2+ biologics (INF, ETA, or ADA only)ADA, ETA, INFSimilar reasons for switching treatments: Lack of efficacy; ADA 54%; ETA 44%; INF 45%. Adverse events: ADA 21%; ETA 22%; INF 34%Fair
*Hyrich et al., 2007250Prospective cohort
6,739
Minimum 6 months
Pts with RA in the British Society for Rheumatology Biologics RegisterADA, ETA, INFDifferences in reason for discontinuation (P=NR): Lack of efficacy; ADA 6.7%; ETA 4.8%; INF 10%. Adverse events: ADA 2.9%; ETA 2.6%; INF 8.4%Fair
*Karanikolas et al., 200893Prospective cohort
128
48 weeks
Pts with RA with inadequate response to traditional DMARDMTX+ ANK
LEF+ANK
No statistically significant differences in number of withdrawals due to adverse eventsFair
Kristensen et al., 2006251Prospective cohort
1,161
Up to 6 years
Pts with RA in southern SwedenETA, ETA+MTX, INF, INF+MTX, other DMARDsEarly discontinuation threefold higher for INF than for ETA (P<.001). Addition of MTX improved treatment continuation rates (P<0.01).Fair
*Marchesoni et al., 2009252
LOHREN
Prospective cohort
1,064
23.32 months
Pts with RA treated with at least one dose of an anti-TNF agentADA, ETA, INFRisk of discontinuation due to adverse events higher for ADA than ETAFair
*Mertens and Singh, 2009134Meta-analysis
2,876
5 trials
Pts with RA included in placebo-controlled RCTsANKNo difference in total number of withdrawals, adverse events, or serious adverse events for ANK vs. placeboFair
*Singh et al., 200927, 180Review of Cochrane reviews and network meta-analysisPts with RAABA, ADA, ANK, ETA, INF, RTXADA, ANK, and INF more likely to have withdrawals due to adverse events vs. ETA: (OR, 1.89; 95% CI, 1.18 to 3.04; OR, 2.05; 95% CI, 1.27 to 3.29; OR, 2.70; 95% CI, 1.43 to 5.26, respectively)Good
*Singh et al., 2010177Systematic review and meta-analysis
8 studies
3,334 patients
8 to 52 weeks
Pts with RATCZFewer overall trial withdrawals with TCZ than placebo; no statistically significant diffence in withdrawals due to adverse eventsFair
*Singh et al., 2010210Systematic review and meta-analysis
4 studies
1,231 patients
20 to 52 weeks
Pts with RAGOL+MTX, MTXFewer overall withdrawals for GOL+MTX than MTX aloneGood
*Weinblatt et al., 200780RCT
121
1 year (LTE: 2 years)
Pts with active RAETA, ABA+ETADiscontinuation due to adverse events occurred more in ABA+ETA group (11.8%) vs. ETA group (2.8%).Good
Zink et al., 200588Retrospective cohort study
1,523
1 year
Pts with RA who had a change in treatment regimenANK, ETA, INF, LEFSignificantly higher overall discontinuation rates for ANK than ETA and INF after 12 months; no differences in discontinuation rates due to adverse eventsGood
*

New study added since last review.

ABA = abatacept; ADA = adalimumab; AE = adverse event; ANK = anakinra; DMARD = disease-modifying antirheumatic drug; ETA = etanercept; GOL = golimumab; INF = infliximab; LEF = leflunomide; LOHREN = Italian Lombardi Rheumatology Network; MTX = methotrexate; NR = not reported; Pts = patients; RA = rheumatoid arthritis; RCT = randomized controlled trial; RTX = rituximab; TCZ = tocilizumab; TNF = tumor necrosis factor

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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