In patients with rheumatoid arthritis and an inadequate response to biologic DMARDs, baricitinib at a daily dose of 4 mg was associated with clinical improvement at 12 weeks. (Funded by Eli Lilly and Incyte; ClinicalTrials.gov number, NCT01721044.).

No abstract

In patients with early rheumatoid arthritis who had a remission while receiving full-dose etanercept-plus-methotrexate therapy, continuing combination therapy at a reduced dose resulted in better disease control than switching to methotrexate alone or placebo, but no significant difference was observed in radiographic progression. (Funded by Pfizer; ClinicalTrials.gov number, NCT00913458.).

No abstract

Background To demonstrate equivalent efficacy of the proposed high-concentration (100 mg/ml), citrate-free adalimumab biosimilar CT-P17 to European Union-approved adalimumab (EU-adalimumab) in subjects with active rheumatoid arthritis (RA). Methods This randomized, double-blind phase III study (ClinicalTrials.gov, NCT03789292) randomized (1:1) subjects with active RA at 52 centers to receive CT-P17 or EU-adalimumab 40 mg subcutaneously every 2 weeks until week 52. Results to week 24 are reported here. The primary endpoint was 20% improvement by American College of Rheumatology criteria (ACR20) response rate at week 24. Equivalence was concluded if the corresponding confidence intervals (CIs) for the estimate of treatment difference were within predefined equivalence margins: − 15 to 15% (95% CI; European Medicines Agency assumption); − 12 to 15% (90% CI; Food and Drug Administration assumption). Additional efficacy, pharmacokinetic, usability, safety, and immunogenicity endpoints were evaluated. Results 648 subjects were randomized (324 CT-P17; 324 EU-adalimumab). The ACR20 response rate at week 24 was 82.7% (n = 268/324) in both groups (intention-to-treat population). The 95% CI (− 5.94 to 5.94) and 90% CI (− 4.98 to 4.98) were within predefined equivalence margins for both assumptions and equivalent efficacy was concluded. Additional endpoints and overall safety were comparable between groups. Mean trough serum concentrations of CT-P17 were slightly higher than those of EU-adalimumab. Immunogenicity was slightly lower numerically for the CT-P17 group than for the EU-adalimumab group. Conclusions CT-P17 and EU-adalimumab have equivalent efficacy and comparable safety and immunogenicity in subjects with active RA. Overall safety of CT-P17 is consistent with the known safety profile of reference adalimumab. Trial registration ClinicalTrials.gov, NCT03789292. Registered 28 December 2018—retrospectively registered.

Objective To compare the safety and efficacy of switching from reference adalimumab to adalimumab biosimilar CT-P17 with continuing reference adalimumab/CT-P17 in active rheumatoid arthritis (RA). Methods This double-blind, phase III study randomised (1:1) subjects with active RA to receive 40 mg (100 mg/ml) CT-P17 or European Union-sourced reference adalimumab subcutaneously every 2 weeks (Q2W) until week (W) 24 (treatment period [TP] 1). Thereafter, subjects receiving reference adalimumab were randomised (1:1) to continue reference adalimumab or switch to CT-P17 from W26 (both Q2W until W48; TP2). Subjects receiving CT-P17 in TP1 continued CT-P17. W0–W24 results were previously reported; we present W26–W52 findings. Endpoints were efficacy (including joint damage progression), pharmacokinetics, safety and immunogenicity. Results Of 607 subjects who initiated TP2 treatment, 303 continued CT-P17, 153 continued reference adalimumab and 151 switched to CT-P17. Efficacy improvements up to W24 were maintained during TP2; efficacy was comparable among groups. At W52, 20% improvement in American College of Rheumatology response rates were 80.5% (continued CT-P17), 77.8% (continued reference adalimumab) and 82.2% (switched to CT-P17). Joint damage progression was minimal. Mean trough serum adalimumab concentrations were similar among groups. CT-P17 and reference adalimumab safety profiles were numerically similar and switching did not affect immunogenicity. At W52, 28.4% (continued CT-P17), 27.0% (continued reference adalimumab) and 28.3% (switched to CT-P17) of subjects were anti-drug antibody-positive. Conclusion Efficacy, pharmacokinetics, safety and immunogenicity of CT-P17 and reference adalimumab were comparable after 1 year of treatment, including after switching from reference adalimumab to CT-P17.

Objective The aim of this study was to investigate long-term clinical outcomes of extended treatment with CT-P10, a rituximab biosimilar, compared with rituximab reference products sourced from the USA and the EU (US-RTX and EU-RTX) in rheumatoid arthritis (RA) for up to 48 weeks. Methods In this multinational, randomized, double-blind trial, adults with active RA received up to two courses of CT-P10, US-RTX, or EU-RTX alongside methotrexate. Efficacy endpoints included Disease Activity Score 28-joint count (DAS28) and American College of Rheumatology (ACR) response rates. Pharmacokinetics, pharmacodynamics, immunogenicity, and safety were also assessed. Results Of 372 patients randomized to the study drug, 330 (88.7%) completed the second treatment course. Mean change from baseline to week 48 in DAS28-C-reactive protein was comparable in the CT-P10 and combined rituximab (US-RTX and EU-RTX) groups (− 2.7 and − 2.6, respectively). ACR20, ACR50, and ACR70 response rates at week 48 indicated no differences between groups (80.6%, 55.4%, and 31.7% vs. 79.8%, 53.9%, and 33.7% in the CT-P10 and combined rituximab groups, respectively). Similar improvements in the Health Assessment Questionnaire Disability Index and all medical outcomes in the Short Form 36-Item Health Survey, including physical and mental health, were seen in all groups. At week 48, antidrug antibodies were detected in 4.9%, 9.4%, and 8.6% of patients in the CT-P10, US-RTX, and EU-RTX groups, respectively. CT-P10 and rituximab displayed similar pharmacokinetic, pharmacodynamic, and safety profiles. Conclusion CT-P10 was similar to EU-RTX and US-RTX in terms of efficacy, pharmacokinetics, pharmacodynamics, immunogenicity, and safety up to week 48. ClinicalTrials.gov identifier NCT02149121. Electronic supplementary material The online version of this article (10.1007/s40259-018-00331-4) contains supplementary material, which is available to authorized users.

BackgroundIn ph 2 studies, baricitinib (bari) improved disease activity with an acceptable safety profile in patients (pts) with active RA naïve to biologic DMARDs (bDMARDs).1,2ObjectivesTo report results from a ph 3 study of bari in pts with active RA and an inadequate response or intolerance to ≥1 TNF inhibitor (TNFi).MethodsPts with active RA (TJC & SJC ≥6, hsCRP ≥3mg/L) on conventional DMARDs (cDMARDs) were randomized 1:1:1 to placebo (PBO) or bari (2 or 4 mg) QD for 24 wks. All bDMARDs were discontinued ≥28d prior to treatment. Primary endpoint was ACR20 response at Wk 12 for bari 4 mg vs. PBO.ResultsOf 527 randomized pts, 57% had received ≥2 bDMARDs and 38% had received ≥1 non-TNFi bDMARD. Fewer pts discontinued treatment prior to Wk 24 on bari 2 or 4 mg vs. PBO (10%, 11%, 18%, respectively). ACR20 response at Wk 12 was higher with bari 4 mg vs. PBO (55% vs. 27%, p≤0.001). Improvements in ACR20, ACR50, ACR70, DAS28, CDAI, SDAI, and HAQ-DI were seen (Table), many as early as Wk 1. Treatment benefit was sustained through Wk 24 for the 4 mg dose. More TEAEs occurred in pts receiving bari 2 or 4 mg compared to PBO (71%, 77%, 64%, respectively) including infections (44%, 40%, 31%, respectively). SAE rates through 24 wks were similar among pts receiving bari 2 or 4 mg or PBO (4%, 10%, and 7%, respectively) including serious infections (2%, 3%, and 3%, respectively). There were no opportunistic infections, TB, or GI perforations. Two non-melanoma skin cancers and 2 major adverse cardiovascular events, including 1 death (stroke), were seen with bari 4 mg. Lab findings were consistent with ph 2 studies. Abnormalities leading to discontinuation were infrequent.Wk 12Wk 24PBO2 mg QD4 mg QDPBO2 mg QD4 mg QD(N=176)(N=174)(N=177)(N=176)(N=174)(N=177)ACR202749***55***2745***46***ACR50820**28***1323*29***ACR70213***11**313***17***DAS28-hsCRP ≤3.2924***32***1120*33***DAS28-hsCRP <2.6411**16***61122***DAS28-ESR ≤3.2413**12**71217**DAS28-ESR <2.616**6*359*CDAI ≤101124**28***152331***CDAI ≤2.8236359*SDAI ≤11922***28***1422*31***SDAI ≤3.3225259**HAQ-DI MCID ≥0.224359**67***3050***53***Data are % patients achieving response (NRI);*p≤0.05,**p≤0.01,***p≤0.001 vs. PBO. ConclusionsIn pts with active RA on cDMARDs and an inadequate response to bDMARDs, once daily oral bari was associated with rapid and sustained clinical improvements through 24 wks, with an acceptable safety and tolerability profile. The largest benefit was seen with the 4 mg dose. Additional ph 3 studies in bDMARD-naive pts are ongoing.ReferencesKeystone et al. Ann Rheum Dis 2015;24:333-340Tanaka et al. Arthritis Rheum 2013;65(S10):S765Disclosure of InterestM. Genovese Grant/research support from: Abbvie, Astellas, Eli Lilly & Company, Galapagos, Pfizer, Vertex, Consultant for: Abbvie, Astellas, Eli Lilly & Company, Galapagos, Pfizer, Vertex, J. Kremer Grant/research support from: Abbvie, Amgen, BMS, Genentech, Eli Lilly & Company, Pfizer, UCB, Consultant for: Eli Lilly & Company, Employee of: Corrona, O. Zamani Grant/research support from: Eli Lilly & Company, C. Lud...