Serious infections during anti-TNFα treatment in rheumatoid arthritis patients

Favalli, Ennio Giulio; Desiati, Francesca; Atzeni, Fabiola; Sarzi-Puttini, Piercarlo; Caporali, Roberto; Bobbio-Pallavicini, Francesca; Gorla, Roberto; Filippini, Matteo; Marchesoni, Antonio

doi:10.1016/j.autrev.2008.11.002

Cited by 145 publications

(137 citation statements)

References 32 publications

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“…Rates for safety events of special interest generally remained stable between phase III and LTE studies and were consistent with the published rates for TNF inhibitors and other biologic DMARD in similar RA populations for mortality 20,21,22 , serious infections including opportunistic infections and tuberculosis 23,24,25,26,27,28,29,30,31,32,33,34,35,36, CV events 37 , and malignancies 38 . Patients with RA are at greater risk than the general population for a number of comorbidities, including CV events and malignancies.…”

Section: Discussionsupporting

confidence: 78%

Safety and Efficacy of Tofacitinib, an Oral Janus Kinase Inhibitor, for the Treatment of Rheumatoid Arthritis in Open-label, Longterm Extension Studies

Wollenhaupt

Silverfield²,

Lee³

et al. 2014

J Rheumatol

284

258

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Objective.To describe the longterm safety and efficacy profile of tofacitinib in patients with moderate to severe active rheumatoid arthritis (RA).Methods.Data were pooled from 2 open-label studies (NCT00413699, NCT00661661) involving patients who had participated in qualifying phase I, II, or III index studies of tofacitinib. Safety data included over 60 months of observation; efficacy data are reported up to Month 48. Treatment was initiated with tofacitinib 5 or 10 mg twice daily. Primary endpoints were adverse events (AE) and laboratory safety data. Secondary endpoints included American College of Rheumatology (ACR) response rates, and Disease Activity Score (28 joints) (DAS28)-4[erythrocyte sedimentation rate (ESR)] and Health Assessment Questionnaire-Disability Index (HAQ-DI) assessments.Results.Overall, 4102 patients were treated for 5963 patient-years; mean (maximum) treatment duration was 531 (1844) days; 20.8% of patients discontinued treatment over 60 months. The most common AE were nasopharyngitis (12.7%) and upper respiratory tract infection (10.5%). Serious AE were reported in 15.4% of patients with an exposure-estimated incidence rate of 11.1 events/100 patient-years. Serious infections were reported in 4.5% of patients with an exposure-estimated incidence rate of 3.1 events/100 patient-years (95% CI: 2.66–3.55). Mean values for laboratory variables were stable over time and consistent with phase II and III studies. Persistent efficacy was demonstrated through Month 48, as measured by ACR response rate (ACR20/50/70) DAS28-4-ESR, and HAQ-DI. Safety and efficacy were similar for patients receiving tofacitinib as monotherapy or with background nonbiologic disease-modifying antirheumatic drugs.Conclusion.Tofacitinib demonstrated consistent safety and persistent efficacy over 48 months in patients with RA.

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Section: Discussionsupporting

confidence: 78%

Safety and Efficacy of Tofacitinib, an Oral Janus Kinase Inhibitor, for the Treatment of Rheumatoid Arthritis in Open-label, Longterm Extension Studies

Wollenhaupt

Silverfield²,

Lee³

et al. 2014

J Rheumatol

284

258

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“…These data are in agreement with the results of Curtis et al who reported a 4-fold greater risk of infections during the first 6 months of infliximab treatment [40]. The most frequently occurring severe infections during infliximab treatment are pulmonary, skin, soft tissue, joint and bone infections, and also septic infections are slightly more probable in RA patients treated with biological agents than in those treated with conventional DMARDs [11][12][13]41]. Oral glucocorticoids ha ve also been reported to elevate the risk of infections in patients with RA even at a dose under 5 mg/day [36,38,39].…”

Section: Other Adverse Eventssupporting

confidence: 90%

“…Traditional DMARDs have been reported to further elevate the risk [36][37][38], but there are also contradictory findings [39]. Biologicals have also a tendency to increase the risk of infections [11,40,41] in RA patients. We observed in the present study a higher number of infections which caused discontinuation of treatment during the first year of the treatment than in the second year.…”

Section: Other Adverse Eventsmentioning

confidence: 99%

Infliximab treatment in patients with rheumatoid arthritis and spondyloarthropathies in one rheumatological center: two years’ drug survival

et al. 2009

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“…In this analysis of infection and mortality data from the global tofacitinib RA clinical development program, the overall rates during tofacitinib therapy appear to be similar to those observed during treatment with biologic agents used in RA (9)(10)(11)(12)(13)(14)(15)(16). The P2P3LTE data set represents the largest population of RA patients treated with tofacitinib for the longest duration of time and is particularly useful for assessing overall rates in the program and over time.…”

Section: Discussionmentioning

confidence: 78%

Analysis of Infections and All‐Cause Mortality in Phase II, Phase III, and Long‐Term Extension Studies of Tofacitinib in Patients With Rheumatoid Arthritis

Cohen

Radominski

Gómez-Reino

et al. 2014

Arthritis & Rheumatology

157

104

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Objective. To determine the rate of infection and all-cause mortality across tofacitinib phase II, phase III, and long-term extension (LTE) studies in patients with moderately to severely active rheumatoid arthritis (RA).Methods. Conclusion. The overall risk of infection (including serious infection) and mortality rates in RA patients treated with tofacitinib appear to be similar to those observed in RA patients treated with biologic agents. The rates of serious infection were stable over time. 550) is an oral JAK inhibitor used for the treatment of rheumatoid arthritis (RA) and has a novel mechanism of action. The JAK family of tyrosine kinases includes JAK-1, JAK-2, JAK-3, and Tyk-2. Tofacitinib preferentially inhibits signaling by heterodimeric receptors associated with JAK-3 and/or JAK-1, with functional selectivity over receptors that signal in pairs of JAK-2 (1). Common ␥-chaincontaining receptors using JAK-1 and JAK-3 include

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Serious infections during anti-TNFα treatment in rheumatoid arthritis patients

Cited by 145 publications

References 32 publications

Safety and Efficacy of Tofacitinib, an Oral Janus Kinase Inhibitor, for the Treatment of Rheumatoid Arthritis in Open-label, Longterm Extension Studies

Safety and Efficacy of Tofacitinib, an Oral Janus Kinase Inhibitor, for the Treatment of Rheumatoid Arthritis in Open-label, Longterm Extension Studies

Infliximab treatment in patients with rheumatoid arthritis and spondyloarthropathies in one rheumatological center: two years’ drug survival

Analysis of Infections and All‐Cause Mortality in Phase II, Phase III, and Long‐Term Extension Studies of Tofacitinib in Patients With Rheumatoid Arthritis

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