ObjectivesTo perform a systematic literature review (SLR) concerning the safety of synthetic(s) and biological (b) disease-modifying antirheumatic drugs (DMARDs) to inform the 2022 update of the... Show moreObjectivesTo perform a systematic literature review (SLR) concerning the safety of synthetic(s) and biological (b) disease-modifying antirheumatic drugs (DMARDs) to inform the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis (RA). MethodsSLR of observational studies comparing safety outcomes of any DMARD with another intervention in RA. A comparator group was required for inclusion. For treatments yet without, or limited, registry data, randomised controlled trials (RCTs) were used. ResultsFifty-nine observational studies addressed the safety of DMARDs. Two studies (unclear risk of bias (RoB)) showed an increased risk of serious infections with bDMARDs compared with conventional synthetic (cs)DMARDs. Herpes zoster infections occurred more with JAKi than csDMARDs (adjusted HR (aHR): 3.66) and bDMARDs (aHR: 1.9-2.3) (four studies, two low RoB). The risk of malignancies was similar across bDMARDs (five studies) and with tofacitinib compared with bDMARDs (one study, low RoB). The risk of major adverse cardiovascular events (MACE) was similar with bDMARDs and tofacitinib (two studies, one low RoB). Thirty studies reported safety from RCTs, with one, designed to evaluate safety, showing that malignancies (HR (95% CI): 1.48 (1.04 to 2.09)) and MACE (HR (95% CI): 1.33 (0.91 to 1.94)) occurred numerically more frequently with tofacitinib (5 mg and 10 mg doses combined) than with TNFi in patients with cardiovascular risk factors. In this study, the risk of venous thromboembolism (VTE) was higher with tofacitinib 10 mg than with TNFi. ConclusionThe safety profile of bDMARDs was further demonstrated. Whether the difference in incidence of malignancies, MACE and VTE between tofacitinib and TNFi applies to other JAKi needs further evaluation. Show less
Chandran, V.; Heijde, D. van der; Fleischmann, R.M.; Lespessailles, E.; Helliwell, P.S.; Kameda, H.; ... ; Gallo, G. 2020
Objective. The aim was to assess the safety and efficacy of up to 156 weeks of ixekizumab (an IL-17A antagonist) treatment in PsA patients.Methods. In a phase III study, patients naive to biologic... Show moreObjective. The aim was to assess the safety and efficacy of up to 156 weeks of ixekizumab (an IL-17A antagonist) treatment in PsA patients.Methods. In a phase III study, patients naive to biologic treatment were randomized to placebo, adalimumab 40 mg every 2 weeks (ADA; active reference) or ixekizumab 80 mg every 2 weeks (IXEQ2W) or every 4 weeks (IXEQ4W) after an initial dose of 160 mg. At week 24 (week 16 for inadequate responders), ADA (after 8-week washout) and placebo patients were re-randomized to IXEQ2W or IXEQ4W. Outcomes were evaluated using a modified non-responder imputation [linear extrapolation for radiographic progression (modified total Sharp score = 0)] during extended treatment until week 156.Results. Of 417 patients, 381 entered the extension, and 243 of 381 (63.8%) completed the 156-week study. Incidence rates of treatment-emergent and serious adverse events, respectively, were 38.0 and 5.2 with IXEQ2W (n =189) and 38.1 and 8.0 with IXEQ4W (n =197). One death occurred (IXEQ4W). With IXEQ2W and IXEQ4W, respectively, the response rates persisted to week 156 as measured by the ACR response >= 20% (62.5 and 69.8%), >= 50% (56.1 and 51.8%) and >= 70% (43.8 and 33.4%), psoriasis area and severity index (PASI) 75 (69.1 and 63.5%), PASI 90 (64.5 and 51.2%) and PASI 100 (60.5 and 43.6%). Inhibition of radiographic progression also persisted to week 156 in 61% of IXEQ2W and 71% of IXEQ4W patients.Conclusion. In this 156-week study of ixekizumab, the safety profile remained consistent with previous reports, and improvements in signs and symptoms of PsA were observed, including persistent low rates of radiographic progression. Show less
Objectives To study whether there is an association between body mass index (BMI) category and survival of various tumour necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA) patients in... Show moreObjectives To study whether there is an association between body mass index (BMI) category and survival of various tumour necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA) patients in a real-life longitudinal international registry.Methods Data from 5230 patients with RA starting treatment with any TNFi were selected from the METEOR registry. Patients were divided into six BMI categories: 3.7% underweight, BMI<18.5 kg/m(2); 46% normal weight, BMI 18.5-25 kg/m(2); 32% pre-obesity, BMI 25-30 kg/m(2); 13% obesity class I, BMI 30-35 kg/m(2); 3.4% obesity class II, BMI 35-40 kg/m(2); and 1.6% obesity class III, BMI >40 kg/m(2). Time on treatment in the different BMI categories was compared for all TNFi combined and for the infliximab, adalimumab and etanercept separately, using Kaplan-Meier curves and Cox regression analyses. Cox regression analyses were adjusted for potential confounders, with follow-up censored at 5000 days.Results Patients in obesity class II (HR 1.28, 95% CI 1.06 to 1.54) and III (HR 1.67, 95% CI 1.29 to 2.18) and underweight patients (HR 1.30, 95% CI 1.07 to 1.58) showed statistically significantly shorter TNFi survival than normal weight patients. The effect in underweight patients was strongest for infliximab (HR 1.82, 95% CI 1.20 to 2.76), the effect in overweight patients was strongest for infliximab (category II (HR 1.49, 95% CI 0.98 to 2.26); category III (HR 1.46, 95% CI 0.79 to 2.71)) and etanercept (category II (HR 1.27 95% CI 0.98 to 1.65); category III (HR 1.79, 95% CI 1.25 to 2.55)). No significant effect modification from reported pain was found.Conclusion Both underweight and overweight patients discontinued TNFi treatment earlier than normal weight patients, without evidence of reported pain as the main determinant. It remains uncertain what determines TNFi survival in individual patients. Show less
