Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response

BackgroundIn SELECT-COMPARE, a randomised double-blind study, upadacitinib 15 mg once daily was superior to placebo or adalimumab on background methotrexate (MTX) for treating rheumatoid arthritis signs and symptoms and inhibited radiographical progression versus placebo at 26 weeks. Here we report 48-week safety and efficacy in patients who continued their original medication or were rescued to the alternative medication for insufficient response.MethodsPatients on MTX received upadacitinib 15 mg, placebo or adalimumab for 48 weeks. Rescue without washout, from placebo or adalimumab to upadacitinib or upadacitinib to adalimumab occurred if patients had <20% improvement in tender joint count (TJC) or swollen joint count (SJC) (weeks 14/18/22) or Clinical Disease Activity Index (CDAI) >10 (week 26); remaining placebo patients were switched to upadacitinib at week 26. Efficacy was analysed by randomised group (non-responder imputation), as well as separately for rescued patients (as observed). Treatment-emergent adverse events per 100 patient-years were summarised.ResultsConsistent with responses through week 26, from weeks 26 to 48, responses by randomised group including low disease activity, clinical remission and improvements in pain and function remained superior for upadacitinib versus adalimumab; radiographical progression remained lower for upadacitinib versus placebo (linear extrapolation). Although both switch groups responded, a higher proportion of patients rescued to upadacitinib from adalimumab achieved CDAI ≤10 at 6 months postswitch versus patients rescued from upadacitinib to adalimumab. Safety at week 48 was comparable to week 26.ConclusionUpadacitinib+MTX demonstrated superior clinical and functional responses versus adalimumab+MTX and maintained inhibition of structural damage versus placebo+MTX through week 48. Patients with an insufficient response to adalimumab or upadacitinib safely achieved clinically meaningful responses after switching to the alternative medication without washout.

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Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: efficacy and safety results of a randomised controlled phase III study

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-219876 ◽

2021 ◽

pp. annrheumdis-2021-219876

Author(s):

Evgeniy Nasonov ◽

Saeed Fatenejad ◽

Eugen Feist ◽

Mariana Ivanova ◽

Elena Korneva ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Activity Index ◽

Disease Activity Index ◽

Phase Iii ◽

Double Blind Study ◽

Efficacy And Safety ◽

Serious Adverse Events ◽

Double Blind ◽

Acr20 Response

ObjectiveTo evaluate the efficacy and safety of olokizumab (OKZ) in patients with active rheumatoid arthritis despite treatment with methotrexate (MTX).MethodsIn this 24-week multicentre, placebo-controlled, double-blind study, patients were randomised 1:1:1 to receive subcutaneously administered OKZ 64 mg once every 2 weeks, OKZ 64 mg once every 4 weeks, or placebo plus MTX. The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. The secondary efficacy endpoints included percentage of subjects achieving Disease Activity Score 28-joint count based on C reactive protein <3.2, Health Assessment Questionnaire Disability Index at week 12, ACR50 response and Clinical Disease Activity Index ≤2.8 at week 24. Safety and immunogenicity were assessed throughout the study.ResultsA total of 428 patients were randomised. ACR20 responses were more frequent with OKZ every 2 weeks (63.6%) and OKZ every 4 weeks (70.4%) than placebo (25.9%) (p<0.0001 for both comparisons). There were significant differences in all secondary efficacy endpoints between OKZ-treated arms and placebo. Treatment-emergent serious adverse events (TESAEs) were reported by more patients in the OKZ groups compared with placebo. Infections were the most common TESAEs. No subjects developed neutralising antidrug antibodies.ConclusionsTreatment with OKZ was associated with significant improvement in signs, symptoms and physical function of rheumatoid arthritis without discernible differences between the two regimens. Safety was as expected for this class of agents. Low immunogenicity was observed.Trial registration numberNCT02760368.

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The Effect of Different Remission Definitions on Identification of Predictors of Both Point and Sustained Remission in Rheumatoid Arthritis Treated with Anti-TNF Therapy

The Journal of Rheumatology ◽

10.3899/jrheum.131451 ◽

2014 ◽

Vol 41 (8) ◽

pp. 1607-1613 ◽

Cited By ~ 14

Author(s):

Cheryl Barnabe ◽

Joanne Homik ◽

Susan G. Barr ◽

Liam Martin ◽

Walter P. Maksymowych

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Activity Index ◽

Disease Activity Index ◽

Joint Disease ◽

Tender Joint Count ◽

Sustained Remission ◽

Tender Joint ◽

Cross Sectional ◽

Das28 Remission

Objective.Predictors of remission in rheumatoid arthritis (RA) have been defined in cross-sectional analyses using the 28-joint Disease Activity Score (DAS28), but not with newer composite disease activity measures or using the more clinically relevant state of sustained remission. We have evaluated predictors of remission using cross-sectional and longitudinal durations of disease state, and by applying additional definitions of remission [American College of Rheumatology/European League Against Rheumatism Boolean, Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI)].Methods.Individuals in the Alberta Biologics Pharmacosurveillance Program were classified for the presence of remission (point and/or sustained > 1 yr) by each of the 4 definitions. Multivariate models were constructed including all available variables in the dataset and refined to optimize model fit and predictive ability to calculate OR for remission.Results.Nonsmoking status independently predicted point remission by all definitions (OR range 1.20–2.71). Minority ethnicity decreased odds of remission by DAS28 (OR 0.13) and CDAI (OR 0.09) definitions. Male sex was associated with DAS28 remission (OR 2.85), whereas higher baseline physician global (OR 0.67) and erythrocyte sedimentation rate values (OR 0.98) decreased odds of DAS28 remission. Higher baseline patient global score (OR 0.77) and swollen joint counts (OR 0.93) were negative predictors for CDAI remission. Higher baseline Health Assessment Questionnaire (OR 0.62) reduced odds for remission by the SDAI definition, and educational attainment increased these odds (OR 2.13). Sustained remission was negatively predicted by baseline physician global for the DAS28 (OR 0.80), and higher tender joint count (OR 0.96) for the CDAI.Conclusion.We demonstrate the influence of duration of remission state and remission definition on defining independent predictors for remission in RA requiring anti-tumor necrosis factor therapy. These predictors offer improved applicability for modern rheumatology practice.

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Predictor of the Simplified Disease Activity Index 50 (SDAI 50) at Month 3 of bDMARD Treatment in Patients with Long-Established Rheumatoid Arthritis

The Open Rheumatology Journal ◽

10.2174/1874312901711010106 ◽

2017 ◽

Vol 11 (1) ◽

pp. 106-112 ◽

Cited By ~ 1

Author(s):

Yusuke Miwa ◽

Mayu Saito ◽

Hidekazu Furuya ◽

Ryo Yanai ◽

Tsuyoshi Kasama

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Odds Ratio ◽

Disease Duration ◽

Activity Index ◽

Short Form ◽

Disease Activity Index ◽

Smoking History ◽

Tender Joint Count ◽

Tender Joint

Objectives:The Simplified Disease Activity Index (SDAI) 50 has good agreement with European League Against Rheumatism (EULAR) response measures for early Rheumatoid Arthritis (RA). There have been reports on early RA, but not on long-established RA. In this study, we analysed the relationships between various baseline factors and SDAI 50 after three months of treatment with biological disease-modifying antirheumatic drugs (bDMARDs) to determine the prognostic factors for long-established RA.Methods:Subjects were 260 RA patients who had been treated with bDMARDs for 3 months. The following characteristics were investigated: Patient backgrounds, the erythrocyte sedimentation rate (ESR), C-reactive protein and serum matrix metalloproteinase-3 levels, SDAI scores, and health assessment questionnaire disability index and short form-36 scores. As a primary outcome index, the SDAI response was defined as a 50% reduction in the SDAI score between baseline and 3 months (SDAI 50).Results:Baseline values of disease duration (odds ratio: 0.942, 95% CI: 0.902-0.984), smoking history (odds ratio: 2.272, 1.064-4.850), 28-tender joint count (odds ratio: 0.899, 0.827-0.977), evaluator's global assessment (odds ratio: 1.029, 1.012-1.047) and ESR (odds ratio: 1.015, 1.001-1.030) were determined to be significant factors based on logistic regression analysis.Conclusion:Our study demonstrated that RA patients with shorter disease duration, no smoking, and higher RA disease activity are more likely to achieve SDAI 50 through bDMARD treatment.

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Evaluation of Serum Calprotectin Level and Disease Activity in Patients with Rheumatoid Arthritis

Current Rheumatology Reviews ◽

10.2174/1573397115666190122113221 ◽

2019 ◽

Vol 15 (4) ◽

pp. 316-320

Author(s):

Mir Amir Aghdashi ◽

Seyedmostafa Seyedmardani ◽

Sholeh Ghasemi ◽

Zohre Khodamoradi

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Inflammatory Arthritis ◽

Unknown Etiology ◽

Tender Joint Count ◽

Serum Samples ◽

Tender Joint ◽

Cross Sectional ◽

Calprotectin Level ◽

Remission Phase

Background: Rheumatoid Arthritis (RA) is the most common type of chronic inflammatory arthritis with unknown etiology marked by a symmetric, peripheral polyarthritis. Calprotectin also can be used as a biomarker of disease activity in inflammatory arthritis and other autoimmune diseases. Objective: In this study, we evaluated the association between serum calprotectin level and severity of RA activity. Methods: A cross-sectional study was conducted on 44 RA patients with disease flare-up. Serum samples were obtained from all patients to measure calprotectin, ESR, CRP prior to starting the treatment and after treatment period in the remission phase. Based on Disease Activity Score 28 (DAS28), disease activity was calculated. Results: Of 44 RA patients, 9(20.5%) were male and 35(79.5%) were female. The mean age of our cases was 53±1.6 years. Seventeen (38.6%) patients had moderate DAS28 and 27(61.4%) had high DAS28. The average level of calprotectin in the flare-up phase was 347.12±203.60 ng/ml and 188.04±23.58 ng/ml in the remission phase. We did not find any significant association between calprotectin and tender joint count (TJC; P=0.22), swollen joint count (SJC; P=0.87), and general health (GH; P=0.59), whereas significant associations were found between the calprotectin level and ESR (p=0.001) and DAS28 (p=0.02). The average calprotectin level in moderate DAS28 (275.21±217.96 ng/ml) was significantly lower than that in high DAS28 (392.4±183.88 ng/ml) (p=0.05). Conclusion: We showed that the serum level of calprotectin can be a useful and reliable biomarker in RA activity and its severity. It also can predict treatment response.

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SAT0046 MODIFIED DISEASE ACTIVITY SCORE AT 3 MONTHS IS A SIGNIFICANT PREDICTOR FOR RAPID RADIOGRAPHIC PROGRESSION AT 12 MONTHS COMPARED WITH OTHER MEASURES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1762 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 954.1-954

Author(s):

M. Movahedi ◽

D. Weber ◽

P. Akhavan ◽

E. Keystone

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Disease Activity Score ◽

Radiographic Progression ◽

Activity Score ◽

Controlled Study ◽

Tender Joint Count ◽

Double Blind ◽

Activity Measures ◽

Disease Activity Measures

Background:Progressive rheumatoid arthritis (RA) is responsible for joint damage causing disabilities with no agreement on which disease measures best predict radiographic progressionObjectives:We aimed to determine which disease activity measures including disease activity score (DAS), modified (M) DAS28 (CRP), clinical disease activity index (CDAI), and health assessment questionnaire disability index (HAQ-DI) best predict rapid radiographic progression (RRP) in early RA patients at baseline (BL) and 3 months.Methods:PREMIER data, a 2-year, multicenter, double-blind active comparator–controlled study with methotrexate (MTX) naïve RA patients and active disease <3 years, were used. Only patients in the MTX arm were analyzed. RRP was defined as change in modified total Sharp (mTSS) > 3.5 at month 12. Logistic regression analysis assessed impact of measures at BL and 3 months on RRP at 12 months. Best cut-off points of M-DAS28(CRP) was also estimated using area under the receiver operating characteristic curve.Results:149 patients were included: female (n=113; 75.8%), positive RF (n=127; 85.2%), mean (SD) age 52.9 (13.3) years, disease duration 0.8 (0.9) year, DAS28(CRP) 6.3 (0.9). After adjusting for potential confounders, only M-DAS28(CRP) at BL (adjOR=3.29; 95% CI: 1.70-6.36) and 3 months (adjOR=2.56; 95% CI: 1.43-4.56) strongly predicted RRP at 12 months. M-DAS28(CRP) 4.5 and 2.6 at BL and 3 months maximized sensitivity and specificity for prediction of RRP.Conclusion:M-DAS28(CRP) was a stronger predictor at BL and 3 months for RRP compared with other disease activity measures. Removing tender joint count and patient global assessment from DAS28(CRP) improves prediction of RRP.References:[1] Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, et al. The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis and rheumatism. 2006;54(1):26-37.Acknowledgments :The authors wish to knowledge AbbVie Canada Inc. for providing patients data.Disclosure of Interests:Mohammad Movahedi Consultant of: Allergan, Deborah Weber: None declared, Pooneh Akhavan: None declared, Edward Keystone Grant/research support from: AbbVie; Amgen; Gilead Sciences, Inc; Lilly Pharmaceuticals; Merck; Pfizer Pharmaceuticals; PuraPharm; Sanofi, Consultant of: AbbVie; Amgen; AstraZeneca Pharma; Bristol-Myers Squibb Company; Celltrion; F. Hoffman-La Roche Ltd.; Genentech, Inc; Gilead Sciences, Inc.; Janssen, Inc; Lilly Pharmaceuticals; Merck; Myriad Autoimmune; Pfizer Pharmaceuticals, Sandoz, Sanofi-Genzyme, Samsung Bioepsis., Speakers bureau: AbbVie; Amgen; Bristol-Myers Squibb; Celltrion; F. Hoffman-La Roche Ltd, Janssen, Inc; Merck; Pfizer Pharmaceuticals; Sanofi-Genzyme; UCB

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Systematic Review and Metaanalysis of Patient Self-Report versus Trained Assessor Joint Counts in Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.090569 ◽

2009 ◽

Vol 36 (12) ◽

pp. 2635-2641 ◽

Cited By ~ 38

Author(s):

JENNIFER L. BARTON ◽

LINDSEY A. CRISWELL ◽

RACHEL KAISER ◽

YEA-HUNG CHEN ◽

DEAN SCHILLINGER

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Pearson Correlation ◽

Correlation Coefficients ◽

Self Report ◽

Future Research ◽

Tender Joint Count ◽

Tender Joint ◽

Trained Assessor ◽

Tender Joint Counts

Objective.Patient self-report outcomes and physician-performed joint counts are important measures of disease activity and treatment response. This metaanalysis examines the degree of concordance in joint counts between trained assessors and patients with rheumatoid arthritis (RA).Methods.Studies eligible for inclusion met the following criteria: English language; compared patient with trained assessor joint counts; peer-reviewed; and RA diagnosis determined by board-certified or board-eligible specialist or met 1987 American College of Rheumatology criteria. We searched PubMed and Embase to identify articles between 1966 and January 1, 2008. We compared measures of correlation between patients and assessors for either tender/painful or swollen joint counts. We used metaanalysis methods to calculate summary correlation estimates.Results.We retrieved 462 articles and 18 were included. Self-report joint counts were obtained by a text and/or mannequin (picture) format. The summary estimates for the Pearson correlation coefficients for tender joint counts were 0.61 (0.47 lower, 0.75 upper) and for swollen joint counts 0.44 (0.15, 0.73). Summary results for the Spearman correlation coefficients were 0.60 (0.30, 0.90) for tender joint counts and 0.54 (0.35, 0.73) for swollen joint counts.Conclusion.A self-report tender joint count has moderate to marked correlation with those performed by a trained assessor. In contrast, swollen joint counts demonstrate lower levels of correlation. Future research should explore whether integrating self-report tender joint counts into routine care can improve efficiency and quality of care, while directly involving patients in assessment of RA disease activity.

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Rate of hypovitaminosis D and association of plasma concentration of 25(OH)D with indicators of disease activity in patients with rheumatoid arthritis

Doklady of the National Academy of Sciences of Belarus ◽

10.29235/1561-8323-2020-64-6-723-729 ◽

2020 ◽

Vol 64 (6) ◽

pp. 723-729

Author(s):

A. V. Rudenko ◽

T. D. Tyabut ◽

A. E. Buglova ◽

G. A. Babak ◽

P. M. Morozik ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Vitamin D ◽

Disease Activity ◽

Vitamin D Deficiency ◽

Activity Index ◽

Serum Vitamin ◽

Disease Activity Index ◽

Tender Joint Count ◽

Serum Vitamin D ◽

Vitamin D Levels

Vitamin D deficiency is an important environmental risk factor that influences the prevalence and severity of several autoimmune diseases, including rheumatoid arthritis (RA). The aim of this study was to determine the incidence of vitamin D insufficiency and deficiency in patients with RA, to establish the relationship between serum vitamin D levels and indicators of disease activity. 156 patients with RA were included in the study, mean age 60.2 ± 13.9 years. Assessment of clinical status was performed, serum concentrations of rheumatoid factor (RF), C-reactive protein (CRP), total vitamin D (25(OH)D), antibodies to cyclic citrullinated peptide (ACCP) were determined. RA disease activity was evaluated using DAS28 (disease activity score), SDAI (Simplified Disease Activity Index) и CDAI (Clinical Disease Activity Index) scores. Average levels of 25(OH)D in the surveyed sample were 25.2 ± 13.2 ng/ml. The results of the study indicate a high prevalence of vitamin D deficiency in patients with RA. Normal indicators of vitamin D, its insufficiency and deficiency were observed in 47 (30.3 %), 45 (28.7 %) and 64 (40.7 %) patients, respectively. Low level of serum 25(OH)D was associated with higher indices of RA activity according to DAS28, SDAI and CDAI, as well as with greater tender joint count. Vitamin D should be prescribed as an adjunctive therapy in patients with active RA due to its potential immunomodulatory effect, as well as for the prevention and treatment of bone metabolism disorders.

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Rheumatoid arthritis activity scores in patients with and without fibromyalgia syndrome

Annals of Saudi Medicine ◽

10.5144/0256-4947.2021.246 ◽

2021 ◽

Vol 41 (4) ◽

pp. 246-252

Author(s):

Yunus Durmaz ◽

Ilker Ilhanli

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Fibromyalgia Syndrome ◽

Conflicts Of Interest ◽

Systemic Disease ◽

Response To Treatment ◽

Unknown Etiology ◽

Tender Joint Count ◽

Tender Joint ◽

Cross Sectional

BACKGROUND: Fibromyalgia syndrome (FM) is a systemic disease of unknown etiology, which can cause widespread musculoskeletal pain. In patients with rheumatoid arthritis (RA), FM can cause an additional symptom burden, which can affect some variables on the RA disease activity score 28 (DAS28), a tool that evaluates 28 joints in RA patients. OBJECTIVE: Compare the results of four different versions of the DAS28 and the parameters used to determine disease activity scores in RA patients with and without FM, and determine whether there are treatment differences between RA patients with and without FM. DESIGN: Retrospective, cross-sectional. SETTING: Tertiary hospital. PATIENTS AND METHODS: We identified patients diagnosed with RA between 1 September 2016 and 1 February 2020 and identified patients with and without FM. MAIN OUTCOME MEASURES: Differences between variables in the DAS28 calculations (tender joint count [TJC], patient global assessment [PGA], and others), between patients with and without FM, and differences between patients with and without FM who were using or not using biological agents. SAMPLE SIZE: 381, including 322 females (84.5%). RESULTS: The frequency of FM in RA patients was 25.7% (89 females, 24.6%). In RA patients with FM, the TJC and PGA median values were significantly higher than in patients without FM ( P <.05). The use of corticosteroids and biological therapy in patients with FM was more frequent than in patients without FM ( P <.05). Compared to patients without FM, patients with FM switched treatment more often because of non-response to treatment ( P =.01) Median values of the DAS28 scores (calculated by four different versions of the instrument) in RA patients with FM were higher than in patients without FM ( P <.05). CONCLUSION: The presence of FM in RA patients may affect the subjective variables in different versions of DAS28 scores, causing the disease activity to score higher on the instrument, erroneously indicating worse disease than is actually present. LIMITATIONS: A single center, retrospective study. CONFLICTS OF INTEREST: None.

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Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2016-210310 ◽

2016 ◽

Vol 76 (5) ◽

pp. 840-847 ◽

Cited By ~ 112

Author(s):

Gerd R Burmester ◽

Yong Lin ◽

Rahul Patel ◽

Janet van Adelsberg ◽

Erin K Mangan ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Active Rheumatoid Arthritis ◽

Activity Index ◽

Joint Disease ◽

Phase Iii ◽

Inadequate Response ◽

Efficacy And Safety ◽

Double Blind ◽

End Point

ObjectivesTo compare efficacy and safety of sarilumab monotherapy with adalimumab monotherapy in patients with active rheumatoid arthritis (RA) who should not continue treatment with methotrexate (MTX) due to intolerance or inadequate response.MethodsMONARCH was a randomised, active-controlled, double-blind, double-dummy, phase III superiority trial. Patients received sarilumab (200 mg every 2 weeks (q2w)) or adalimumab (40 mg q2w) monotherapy for 24 weeks. The primary end point was change from baseline in 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) at week 24.ResultsSarilumab was superior to adalimumab in the primary end point of change from baseline in DAS28-ESR (−3.28 vs −2.20; p<0.0001). Sarilumab-treated patients achieved significantly higher American College of Rheumatology 20/50/70 response rates (sarilumab: 71.7%/45.7%/23.4%; adalimumab: 58.4%/29.7%/11.9%; all p≤0.0074) and had significantly greater improvement in Health Assessment Questionnaire-Disability Index (p=0.0037). Importantly, at week 24, more patients receiving sarilumab compared with adalimumab achieved Clinical Disease Activity Index remission (7.1% vs 2.7%; nominal p=0.0468) and low disease activity (41.8% vs 24.9%; nominal p=0.0005, supplemental analysis). Adverse events occurred in 63.6% (adalimumab) and 64.1% (sarilumab) of patients, the most common being neutropenia and injection site reactions (sarilumab) and headache and worsening RA (adalimumab). Incidences of infections (sarilumab: 28.8%; adalimumab: 27.7%) and serious infections (1.1%, both groups) were similar, despite neutropenia differences.ConclusionsSarilumab monotherapy demonstrated superiority to adalimumab monotherapy by improving the signs and symptoms and physical functions in patients with RA who were unable to continue MTX treatment. The safety profiles of both therapies were consistent with anticipated class effects.Trial registration numberNCT02332590.

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Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficient response: efficacy and safety in patients with rheumatoid arthritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-218412 ◽

2020 ◽

pp. annrheumdis-2020-218412

Author(s):

Roy M Fleischmann ◽

Ricardo Blanco ◽

Stephen Hall ◽

Glen T D Thomson ◽

Filip E Van den Bosch ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Kinase Inhibitor ◽

Activity Index ◽

Disease Activity Index ◽

Initial Therapy ◽

Janus Kinase ◽

Treat To Target ◽

Efficacy And Safety ◽

Insufficient Response

ObjectivesTo evaluate efficacy and safety of immediate switch from upadacitinib to adalimumab, or vice versa, in patients with rheumatoid arthritis with non-response or incomplete-response to the initial therapy.MethodsSELECT-COMPARE randomised patients to upadacitinib 15 mg once daily (n=651), placebo (n=651) or adalimumab 40 mg every other week (n=327). A treat-to-target study design was implemented, with blinded rescue occurring prior to week 26 for patients who did not achieve at least 20% improvement in both tender and swollen joint counts (‘non-responders’) and at week 26 based on Clinical Disease Activity Index (CDAI) >10 (‘incomplete-responders’) without washout.ResultsA total of 39% (252/651) and 49% (159/327) of patients originally randomised to upadacitinib and adalimumab were rescued to the alternate therapy. In both switch groups (adalimumab to upadacitinib and vice versa) and in non-responders and incomplete-responders, improvements in disease activity were observed at 3 and 6 months following rescue. CDAI low disease activity was achieved by 36% and 47% of non-responders and 45% and 58% of incomplete-responders switched to adalimumab and upadacitinib, respectively, 6 months following switch. Overall, approximately 5% of rescued patients experienced worsening in disease activity at 6 months postswitch. The frequency of adverse events was similar between switch groups.ConclusionsThese observations support a treat-to-target strategy, in which patients who fail to respond initially (or do not achieve sufficient response) are switched to a therapy with an alternate mechanism of action and experience improved outcomes. No new safety findings were observed despite immediate switch without washout.

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