Safety and efficacy of switching from adalimumab to sarilumab in patients with rheumatoid arthritis in the ongoing MONARCH open-label extension

Abstract

ObjectiveEvaluate open-label sarilumab monotherapy in patients with rheumatoid arthritis switching from adalimumab monotherapy in MONARCH (NCT02332590); assess long-term safety and efficacy in patients continuing sarilumab during open-label extension (OLE).MethodsDuring the 48-week OLE, patients received sarilumab 200 mg subcutaneously once every 2 weeks. Safety (March 2017 cut-off) and efficacy, including patient-reported outcomes, were evaluated.ResultsIn the double-blind phase, patients receiving sarilumab or adalimumab monotherapy showed meaningful improvements in disease activity; sarilumab was superior to adalimumab for improving signs, symptoms and physical function. Overall, 320/369 patients completing the 24-week double-blind phase entered OLE (155 switched from adalimumab; 165 continued sarilumab). Sarilumab safety profile was consistent with previous reports. Treatment-emergent adverse events were similar between groups; no unexpected safety signals emerged in the first 10 weeks postswitch. Among switch patients, improvement in disease activity was evident at OLE week 12: 47.1%/34.8% had changes ≥1.2 in Disease Activity Score (28 joints) (DAS28)-erythrocyte sedimentation rate/DAS28-C-reactive protein. In switch patients achieving low disease activity (LDA: Clinical Disease Activity Index (CDAI) ≤10; Simplified Disease Activity Index (SDAI) ≤11) by OLE week 24, 70.7%/69.5% sustained CDAI/SDAI LDA at both OLE weeks 36 and 48. Proportions of switch patients achieving CDAI ≤2.8 and SDAI ≤3.3 by OLE week 24 increased through OLE week 48. Improvements postswitch approached continuation-group values, including scores ≥normative values.ConclusionsDuring this OLE, there were no unexpected safety issues in patients switching from adalimumab to sarilumab monotherapy, and disease activity improved in many patients. Patients continuing sarilumab reported safety consistent with prolonged use and had sustained benefit.

Safety of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis

“…From a total of 2961 references (after de-duplication), 226 were selected for a full-text review and 59 observational studies fulfilled the inclusion criteria 16–74. In addition, 2 RCTs with a primary safety outcome,2 3 and 28 RCTs/LTEs from the efficacy SLR,75–102 were included (flow chart in online supplemental figure S1). Studies were heterogeneous, precluding data pooling, and results are presented descriptively.…”

“…Eleven studies evaluating bDMARDs,2 75 76 78 79 84 87 90 92 96 100 and 19 evaluating tsDMARDs were included (online supplemental tables S138–152). 3 77 80–83 85 86 88 89 91 93–95 97–99 101 102 Most RCTs were not designed, and therefore, not powered, to evaluate safety outcomes.…”

Interleukin-6 in Rheumatoid Arthritis

“…Another IL-6 R inhibitor, sarilumab (SAR), has also been approved in RA in combination with MTX [ 74 , 75 , 76 , 77 , 78 ]. In the MONARCH study, it was demonstrated that SAR monotherapy was more efficient than adalimumab (an anti-TNFα) monotherapy, improving signs and symptoms and physical functions in patients with RA who could not continue taking MTX [ 79 ]. In addition, atlizumab, an IL-6R inhibitor, was proven to be beneficial [ 80 ].…”

A double-blind, double-dummy, randomized controlled, multicenter trial of 99Tc-methylene diphosphonate in patients with moderate to severe rheumatoid arthritis

“…[ 2 ] When patients fail to initial treatments, biologic (b) DMARDs and targeted synthesis DMARDs (such as Janus kinase [JAK] inhibitors) are usually considered. [ 3 – 5 ] Although these drugs effectively control the disease activity of patients with RA, there is still a significant unmet need in the field of RA, especially for those at high risk of bone structural damage.…”

“…[2] When patients fail to initial treatments, biologic (b) DMARDs and targeted synthesis DMARDs (such as Janus kinase [JAK] inhibitors) are usually considered. [3][4][5] Although these drugs effectively control the disease activity of patients with RA, there is still a significant unmet need in the field of RA, especially for those at high risk of bone structural damage. 99 Tc-methylene diphosphonate ( 99 Tc-MDP), a chemical compound of technetium-99 conjugated with methylene diphosphonate ([ 99 Tc-MDP], or Yunke, Chengdu Yunke Pharmaceutical Co., Ltd., Chengdu, Sichuan, China), is an anti-inflammatory and anti-bone destruction drug patented in China (patent No.…”