Introduction: The efficacy of sarilumab and upadacitinib, in combination with disease-modifying antirheumatic drugs (DMARDs), was demonstrated in phase 3 clinical trials of patients with rheumatoid... Show moreIntroduction: The efficacy of sarilumab and upadacitinib, in combination with disease-modifying antirheumatic drugs (DMARDs), was demonstrated in phase 3 clinical trials of patients with rheumatoid arthritis (RA) refractive to previous biologic DMARDs. In the absence of head-to-head clinical trials, the matching-adjusted indirect comparison (MAIC) and simulated treatment comparison (STC) estimate the relative efficacy of sarilumab and upadacitinib in patients with RA who had an inadequate response to previous biologic DMARDs. Methods:Patient-level data for sarilumab were obtained from the TARGET trial (NCT01709578) and published aggregate data for upadacitinib were obtained from the SELECT-BEYOND trial (NCT02706847). For the MAIC, individual patient data from the TARGET trial were assigned weights such that weighted mean baseline characteristics of the treatment effect modifiers matched those from SELECT-BEYOND. For the STC, the TARGET patient-level data and mean baseline values from SELECT-BEYOND were used to simulate sarilumab treatment effects for a SELECT-BEYOND population. Endpoints evaluated included the American College of Rheumatology (ACR) response criteria ACR20/50/70, Disease Activity Score-28 for Rheumatoid Arthritis with C-reactive protein (DAS28-CRP) < 3.2, DAS28-CRP < 2.6, Simple Disease Activity Index (SDAI) < 3.3, and Clinical Disease Activity Index (CDAI) < 2.8 at 12 weeks. Results: The analysis included 365 patients from TARGET and aggregated data of 333 patients from SELECT-BEYOND. Matching for potential treatment effect baseline modifiers (i.e., age, oral glucocorticoid use, tender joint count of 68 counts, swollen joint count of 66 counts, serum CRP level, and patient global assessment of disease activity) resulted in a reduction of the effective sample size of TARGET population to 166. Following MAIC and STC analysis, the odds of achieving all aforementioned clinical outcomes versus placebo at week 12 were similar for sarilumab and upadacitinib. Conclusion: In the MAIC and STC analyses from TARGET and SELECT-BEYOND trials, the efficacy of sarilumab and upadacitinib were comparable. Show less
Huizinga, T.; Choy, E.; Praestgaard, A.; Hoogstraten, H. van; LaFontaine, P.R.; Guyot, P.; ... ; Fleischmann, R. 2023
IntroductionThe efficacy of sarilumab and upadacitinib, in combination with disease-modifying antirheumatic drugs (DMARDs), was demonstrated in phase 3 clinical trials of patients with rheumatoid... Show moreIntroductionThe efficacy of sarilumab and upadacitinib, in combination with disease-modifying antirheumatic drugs (DMARDs), was demonstrated in phase 3 clinical trials of patients with rheumatoid arthritis (RA) refractive to previous biologic DMARDs. In the absence of head-to-head clinical trials, the matching-adjusted indirect comparison (MAIC) and simulated treatment comparison (STC) estimate the relative efficacy of sarilumab and upadacitinib in patients with RA who had an inadequate response to previous biologic DMARDs.MethodsPatient-level data for sarilumab were obtained from the TARGET trial (NCT01709578) and published aggregate data for upadacitinib were obtained from the SELECT-BEYOND trial (NCT02706847). For the MAIC, individual patient data from the TARGET trial were assigned weights such that weighted mean baseline characteristics of the treatment effect modifiers matched those from SELECT-BEYOND. For the STC, the TARGET patient-level data and mean baseline values from SELECT-BEYOND were used to simulate sarilumab treatment effects for a SELECT-BEYOND population. Endpoints evaluated included the American College of Rheumatology (ACR) response criteria ACR20/50/70, Disease Activity Score-28 for Rheumatoid Arthritis with C-reactive protein (DAS28-CRP) < 3.2, DAS28-CRP < 2.6, Simple Disease Activity Index (SDAI) < 3.3, and Clinical Disease Activity Index (CDAI) < 2.8 at 12 weeks.ResultsThe analysis included 365 patients from TARGET and aggregated data of 333 patients from SELECT-BEYOND. Matching for potential treatment effect baseline modifiers (i.e., age, oral glucocorticoid use, tender joint count of 68 counts, swollen joint count of 66 counts, serum CRP level, and patient global assessment of disease activity) resulted in a reduction of the effective sample size of TARGET population to 166. Following MAIC and STC analysis, the odds of achieving all aforementioned clinical outcomes versus placebo at week 12 were similar for sarilumab and upadacitinib.ConclusionIn the MAIC and STC analyses from TARGET and SELECT-BEYOND trials, the efficacy of sarilumab and upadacitinib were comparable. Show less
Objective Sarilumab, as monotherapy or in combination with conventional synthetic DMARDs, such as MTX, has demonstrated improvement in clinical outcomes in patients with RA. The primary objective... Show moreObjective Sarilumab, as monotherapy or in combination with conventional synthetic DMARDs, such as MTX, has demonstrated improvement in clinical outcomes in patients with RA. The primary objective of this post hoc analysis was to compare the efficacy of sarilumab (200 mg every 2 weeks) monotherapy (MONARCH study) with that of sarilumab and MTX combination therapy (MOBILITY study) at week 24. Methods The endpoints assessed were mean change from baseline in the Clinical Disease Activity Index (CDAI), 28-joint Disease Activity using CRP (DAS28-CRP), CRP, haemoglobin (Hb), pain visual analogue scale (VAS) and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue. Least square (LS) mean change from baseline (95% CI) at week 24 for all endpoints was compared between the treatment arms for adjusted comparisons. Results This analysis included 184 patients on sarilumab monotherapy and 399 patients on sarilumab plus MTX. Differences (P < 0.05) were observed in ethnicity, region, body mass index group, rheumatoid factor, anti-cyclic citrullinated peptide antibodies, swollen joint count, CRP, CDAI and oral glucocorticoid use between these treatment groups. After adjusting for these differences in a mixed-effect model repeated measure, LS mean change from baseline for all assessments was similar between the treatment groups with overlapping CIs: CDAI, -28.79 vs -26.21; DAS28-CRP, -2.95 vs -2.81; CRP, -18.31 vs -16.46; Hb, 6.59 vs 8.09; Pain VAS, -33.62 vs -31.66; FACIT-Fatigue, 9.90 vs 10.24. Conclusion This analysis demonstrated that the efficacy of sarilumab monotherapy was similar to that of sarilumab and MTX combination therapy. Show less
