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1.
Arthritis Rheumatol ; 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33779069

RESUMO

The ideal state for a patient with rheumatoid arthritis (RA) is sustained remission. Contemporary treatment strategies such as early initiation of DMARD(s), optimal methotrexate dosing and treating to a target with validated outcomes have improved the likelihood of remission in RA. Remission, however defined, is not always achieved and even less often will patients with RA maintain sustained remission over time.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33644992

RESUMO

OBJECTIVE: Responsive assessment of disease activity in patients with rheumatoid arthritis (RA) is necessary to evaluate therapeutic efficacy and guide treatment. We compared the utility of the multi-biomarker disease activity (MBDA) score in assessing RA disease activity with that of the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) and the Clinical Disease Activity Index (CDAI) in a multicenter, randomized, placebo-controlled trial of repository corticotropin injection (RCI) in patients with persistently active RA. METHODS: Patients received 80 U of RCI twice weekly during a 12-week open-label period; those who achieved low disease activity at week 12 were randomly assigned to receive either 80 U of RCI or placebo twice weekly during a 12-week double-blind period. Changes in disease activity (measured by DAS28-ESR, CDAI, and MBDA) and correlations between MBDA scores and both DAS28-ESR and CDAI scores were assessed. RESULTS: Changes from baseline in DAS28-ESR and CDAI scores suggested that RCI therapy led to clinically meaningful improvements in disease activity, but improvements from baseline in MBDA scores were below the minimally important difference threshold. For the DAS28-ESR and CDAI, correlations with total MBDA and individual component scores were generally low (r≤0.3), occasionally moderate (r>0.3 but <0.5). CONCLUSION: Our results suggest overall MBDA scores are not sufficiently responsive for assessing RA disease activity after RCI therapy. These findings are consistent with those seen with other RA drugs and, although they are from a clinical trial, suggest the MBDA should not be a preferred disease activity measure in clinical practice.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33590829

RESUMO

OBJECTIVE: To evaluate the impact of upadacitinib vs placebo and adalimumab treatment, on patient-reported outcomes (PROs) in SELECT-COMPARE in an active RA population with inadequate responses to methotrexate (MTX-IR). METHODS: PROs in patients receiving upadacitinib (15 mg QD), placebo, or adalimumab (40 mg EOW) while on background MTX were evaluated over 48 weeks. PROs included PtGA and pain by VAS, HAQ-DI, 36-Item Short Form Survey (SF-36), morning (AM) stiffness duration and severity, FACIT-F, and work instability. Least squares mean (LSM) changes and proportions of patients reporting improvements ≥ minimal clinically important differences (MCID) and scores ≥ normative values were evaluated. RESULTS: Upadacitinib and adalimumab resulted in greater LSM changes from baseline vs placebo across all PROs (p < 0.05) at week 12, and pain and AM stiffness severity (p < 0.05) at week 2. More upadacitinib- vs placebo-treated (p < 0.05) and similar percentages of upadacitinib- vs adalimumab-treated patients reported improvements ≥ MCID across all PROs at week 12. Upadacitinib vs adalimumab resulted in greater LSM changes from baseline in PtGA, pain, HAQ-DI, stiffness severity, FACIT-F, and SF-36 Physical Component Summary (PCS) (all p < 0.05) at week 12. More upadacitinib- vs adalimumab-treated patients reported scores ≥ normative values in HAQ-DI and SF-36 PCS (p < 0.05) at week 12. More upadacitinib- vs adalimumab-treated patients maintained clinically meaningful improvements in PtGA, pain, HAQ-DI, FACIT-F, and AM stiffness through 48 weeks. CONCLUSION: In MTX-IR patients with RA, treatment with upadacitinib resulted in statistically significant and clinically meaningful improvements in PROs equivalent to or greater than with adalimumab.

4.
RMD Open ; 6(3)2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33188136

RESUMO

OBJECTIVES: Review of efficacy and safety of Janus kinase (JAK) inhibition in immune-mediated inflammatory diseases (IMIDs). METHODS: A systematic literature research (SLR) of all publications on JAK inhibitors (JAKi) treatment published until March 2019 using MEDLINE, EMBASE and the Cochrane Library. Efficacy and safety were assessed in randomised controlled trials (RCTs), integrating long-term extension periods additionally for safety evaluation. RESULTS: 3454 abstracts were screened with 85 included in the final analysis (efficacy and RCT safety: n=72; safety only: n=13). Efficacy of RCTs investigating tofacitinib (TOFA, n=27), baricitinib (BARI, n=9), upadacitinib (UPA, n=14), filgotinib (FILGO, n=7), decernotinib (DEC, n=3) and peficitinib (PEF, n=7) was evaluated. Six head-to-head trials comparing JAKi with tumour necrosis factor inhibitors (TNFi) were included. Efficacy of JAKi was shown in rheumatoid arthritis (RA) for all agents, psoriatic arthritis (TOFA, FILGO), ankylosing spondylitis (TOFA, FILGO), systemic lupus erythematosus (BARI), chronic plaque psoriasis (TOFA, BARI, PEF), ulcerative colitis (TOFA, UPA), Crohn's disease (UPA, FILGO) and atopic dermatitis (TOFA, BARI, UPA). Safety analysis of 72 RCTs, one cohort study and 12 articles on long-term extension studies showed increased risks for infections, especially herpes zoster, serious infections and numerically higher rates of venous thromboembolic events. No increased malignancy rates or major adverse cardiac events were observed. CONCLUSION: JAKi provide good efficacy compared to placebo (and to TNFi in RA and Pso) across various IMIDs with an acceptable safety profile. This SLR informed the task force on points to consider for the treatment of IMIDs with JAKi with the available evidence.

5.
Ann Rheum Dis ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33158881

RESUMO

OBJECTIVES: Janus kinase inhibitors (JAKi) have been approved for use in various immune-mediated inflammatory diseases. With five agents licensed, it was timely to summarise the current understanding of JAKi use based on a systematic literature review (SLR) on efficacy and safety. METHODS: Existing data were evaluated by a steering committee and subsequently reviewed by a 29 person expert committee leading to the formulation of a consensus statement that may assist the clinicians, patients and other stakeholders once the decision is made to commence a JAKi. The committee included patients, rheumatologists, a gastroenterologist, a haematologist, a dermatologist, an infectious disease specialist and a health professional. The SLR informed the Task Force on controlled and open clinical trials, registry data, phase 4 trials and meta-analyses. In addition, approval of new compounds by, and warnings from regulators that were issued after the end of the SLR search date were taken into consideration. RESULTS: The Task Force agreed on and developed four general principles and a total of 26 points for consideration which were grouped into six areas addressing indications, treatment dose and comedication, contraindications, pretreatment screening and risks, laboratory and clinical follow-up examinations, and adverse events. Levels of evidence and strengths of recommendations were determined based on the SLR and levels of agreement were voted on for every point, reaching a range between 8.8 and 9.9 on a 10-point scale. CONCLUSION: The consensus provides an assessment of evidence for efficacy and safety of an important therapeutic class with guidance on issues of practical management.

6.
Ann Rheum Dis ; 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33148701

RESUMO

OBJECTIVES: To 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. METHODS: SELECT-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. RESULTS: A 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. CONCLUSIONS: These 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.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33123205

RESUMO

Background: In the randomized, phase III, global SELECT-COMPARE study, upadacitinib 15 mg demonstrated efficacy at week 12 versus placebo and adalimumab with methotrexate (MTX) in patients with rheumatoid arthritis and inadequate response to MTX, which was maintained over 48 weeks. This post hoc analysis of SELECT-COMPARE reports the efficacy and safety of upadacitinib in Central and Eastern European (CEE) patients. Methods: Patients were randomized 2:2:1 to upadacitinib 15 mg once daily, placebo, or adalimumab 40 mg every other week, and continued MTX. Efficacy and safety were assessed through 48 weeks. Primary endpoints were the achievement of ≥20% improvement in American College of Rheumatology response criteria and Disease Activity Score in 28 joints with C-reactive protein <2.6 responses at week 12 for upadacitinib versus placebo. No statistical comparisons were conducted. Results: A total of 596 patients from 12 CEE countries were randomized. At week 12, a numerically greater proportion of patients receiving upadacitinib versus placebo or adalimumab achieved ≥20% improvement in American College of Rheumatology response criteria (72% versus 33% and 59%), Disease Activity Score in 28 joints with C-reactive protein <2.6 (26% versus 4% and 11%), low disease activity and remission, and improved physical function, with results maintained over 48 weeks. Upadacitinib treatment numerically inhibited structural progression versus placebo at week 26. Serious infection and herpes zoster rates were numerically higher with upadacitinib versus adalimumab (2.7 versus 1.7 and 2.3 versus 1.1 events/100 patient-years, respectively) over 48 weeks. Conclusion: Consistent with the global population of patients with rheumatoid arthritis and an inadequate response to MTX, in CEE patients, upadacitinib 15 mg demonstrated clinical and functional improvements versus placebo and adalimumab, radiographic improvements versus placebo, and reasonable safety, over 48 weeks.

8.
Arthritis Res Ther ; 22(1): 206, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907617

RESUMO

BACKGROUND: Diabetes is common in patients with rheumatoid arthritis (RA). Interleukin (IL)-6 is implicated in both the pathogenesis of RA and in glucose homeostasis; this post hoc analysis investigated the effects of IL-6 receptor vs. tumour necrosis factor inhibition on glycosylated haemoglobin (HbA1c) in patients with RA with or without diabetes. METHODS: Data were from two placebo-controlled phase III studies of subcutaneous sarilumab 150/200 mg q2w + methotrexate or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and a phase III monotherapy study of sarilumab 200 mg q2w vs. adalimumab 40 mg q2w. Patients with diabetes were identified by medical history or use of antidiabetic medication (patients with HbA1c ≥ 9% were excluded from all three studies). HbA1c was measured at baseline and weeks 12/24. Safety and efficacy were assessed in RA patients with or without diabetes. RESULTS: Patients with diabetes (n = 184) were older, weighed more and exhibited higher RA disease activity than patients without diabetes (n = 1928). Regardless of diabetes status, in patients on background csDMARDs, least squares (LS) mean difference (95% CI) in change from baseline in HbA1c for sarilumab 150 mg/200 mg vs. placebo at week 24 was - 0.28 (- 0.40, - 0.16; nominal p <  0.0001) and - 0.42 (- 0.54, - 0.31; nominal p <  0.0001), respectively. Without csDMARDs, LS mean difference for sarilumab 200 mg vs. adalimumab 40 mg at week 24 was - 0.13 (- 0.22, - 0.04; nominal p = 0.0043). Greater reduction in HbA1c than placebo or adalimumab was observed at week 24 with sarilumab in patients with diabetes and/or baseline HbA1c ≥ 7%. There was no correlation between baseline/change from baseline in HbA1c and baseline/change from baseline in C-reactive protein, 28-joint Disease Activity Score, or haemoglobin, nor between HbA1c change from baseline and baseline glucocorticoid use. Medical history of diabetes or use of diabetes treatments had limited impact on safety and efficacy of sarilumab and was consistent with overall phase III findings in patients with RA. CONCLUSIONS: In post hoc analyses, sarilumab was associated with a greater reduction in HbA1c than csDMARDs or adalimumab, independent of sarilumab anti-inflammatory effects. Prospective studies are required to further assess these preliminary findings. TRIAL REGISTRATION: ClinTrials.gov NCT01061736: date of registration February 03, 2010; ClinTrials.gov NCT01709578: date of registration October 18, 2012; ClinTrials.gov NCT02332590: date of registration January 07, 2015.

9.
Ann Rheum Dis ; 79(10): 1290-1297, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32788396

RESUMO

OBJECTIVES: To evaluate the incidence of infection in patients with active rheumatoid arthritis (RA) treated with baricitinib, an oral selective Janus kinase (JAK)1 and JAK2 inhibitor. METHODS: Infections are summarised from an integrated database (8 phase 3/2/1b clinical trials and 1 long-term extension (LTE)) with data to 1 April 2017. The 'all-bari-RA' analysis set included patients who received any baricitinib dose. Placebo comparison was based on six studies with 4 mg and placebo to week 24, including four trials with 2 mg (placebo-controlled set). Dose-response assessment was based on four studies with 2 mg and 4 mg, including LTE data (2-4 mg extended set). RESULTS: There were 3492 patients who received baricitinib for 7860 patient-years (PY) of exposure (median 2.6 years, maximum 6.1 years). Treatment-emergent infections were higher for baricitinib versus placebo (exposure-adjusted incidence rate (IR)/100 PY: placebo 75.9, 2 mg 84.0 (p not significant), 4 mg 88.4 (p≤0.001)). The IR of serious infection was similar for baricitinib versus placebo and stable over time (all-bari-RA IR 3.0/100 PY). There were 11 cases of tuberculosis (all-bari-RA IR 0.1/100 PY); all occurred with 4 mg in endemic regions. Herpes zoster (HZ) IR/100 PY was higher for baricitinib versus placebo (placebo 1.0, 2 mg 3.1 (p not significant), 4 mg 4.3 (p≤0.01)); rates remained elevated and stable over time (all-bari-RA 3.3). Opportunistic infections, including multidermatomal HZ, were infrequent in the baricitinib programme (all-bari-RA IR 0.5/100 PY). CONCLUSIONS: Increased rates of treatment-emergent infections including HZ were observed in patients with RA treated with baricitinib, consistent with baricitinib's immunomodulatory mode of action.


Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Azetidinas/efeitos adversos , Hospedeiro Imunocomprometido , Infecções/imunologia , Sulfonamidas/efeitos adversos , Método Duplo-Cego , Humanos , Incidência , Infecções/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos
10.
J Clin Med ; 9(6)2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32604962

RESUMO

To date, the impact of background glucocorticoids (GC) on the efficacy and safety of abatacept or adalimumab in patients with active rheumatoid arthritis (RA) is not clearly established. This post hoc analysis of (AMPLE) trial (NCT00929864) compared efficacy and safety outcomes over 2 years in patients treated with abatacept or adalimumab plus background methotrexate (MTX), who continued GC (≤10 mg/day) versus those who were not receiving GC (no-GC). Of 646 randomized patients, 317 received abatacept + MTX (161 GC, 156 no-GC) and 326 received adalimumab + MTX (162 GC, 164 no-GC). At Year 2, the adjusted mean changes from baseline in Disease Activity Score (DAS28 C-reactive protein (CRP)) and Health Assessment Questionnaire-Disability Index (HAQ-DI) were not significantly different in the GC versus no-GC subgroups receiving abatacept or adalimumab. A similar proportion of patients achieved remission, HAQ-DI score improvement ≥0.3 and radiographic progression rates. No clinically meaningful safety differences were observed between GC versus no-GC subgroups either with abatacept or adalimumab. In patients with active RA of similar baseline disease activity treated with abatacept or adalimumab plus background MTX, there was no additional value of background GC on clinical, functional or radiographic outcomes over two years.

11.
Arthritis Res Ther ; 22(1): 139, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32522251

RESUMO

BACKGROUND: The interleukin-6 receptor inhibitor sarilumab demonstrated efficacy in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or as monotherapy in patients with moderately to severely active rheumatoid arthritis (RA) with an inadequate response (IR) or intolerant (INT) to methotrexate (MTX) or tumour necrosis factor (TNF)-α inhibitors. This analysis investigated the efficacy and safety of sarilumab in patient subgroups. METHODS: Data were included from phase III studies: two placebo-controlled studies of subcutaneous sarilumab 150/200 mg every 2 weeks (q2w) either + MTX in MTX-IR patients (52 weeks) or + csDMARDs in TNF-IR/INT patients (24 weeks), and a monotherapy study of sarilumab 200 mg q2w vs. adalimumab 40 mg q2w in MTX-IR/INT patients (24 weeks). Prespecified and post hoc subgroups included patient demographics, disease characteristics, and prior treatments. Prespecified and post hoc endpoints included clinical, radiographic, and physical function measures, and p values are considered nominal. Safety was assessed during double-blind treatment. RESULTS: The superiority of sarilumab (either as monotherapy vs. adalimumab or in combination with csDMARDs vs. placebo + csDMARDs) across clinical endpoints was generally consistent across subgroups defined by patient demographics, disease characteristics, and prior treatments, demonstrating the benefit of sarilumab treatment for a wide range of patient types. Interaction p values of < 0.05 were consistently observed across studies only for baseline anti-cyclic citrullinated peptide antibody (ACPA) status for American College of Rheumatology 20% response, but not American College of Rheumatology 50% or 70% response. Adverse events and worsening laboratory parameters occurred more frequently in sarilumab-treated vs. placebo-treated patients and were more frequent in the small number of patients ≥ 65 years (n = 289) vs. patients < 65 years (n = 1819). Serious infections occurred in six patients aged ≥ 65 years receiving sarilumab, although the incidence of serious infections was generally higher in patients aged ≥ 65 years regardless of treatment. CONCLUSIONS: Apart from ACPA status, there were no consistent signals indicating differential effects of sarilumab in any of the subpopulations assessed. Sarilumab demonstrated consistent efficacy and safety across a wide range of patients with RA. TRIAL REGISTRATION: ClinicalTrials.gov NCT01061736, registered on February 03, 2010; ClinicalTrials.gov NCT01709578, registered on October 18, 2012; ClinicalTrials.gov NCT02332590, registered on January 07, 2015.

12.
Expert Opin Drug Saf ; 19(8): 935-944, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32497440

RESUMO

INTRODUCTION: Disease-modifying antirheumatic drugs (DMARDs) have significantly improved clinical symptoms and quality of life with reduced disease progression in many patients with rheumatoid arthritis (RA). Short-term glucocorticoid therapy is often used initially in combination with DMARDs, but some patients still have difficulty reaching treatment goals. Repository corticotropin injection (RCI, Acthar® Gel) is approved as adjunctive therapy for short-term administration in patients with continued RA disease activity. AREAS COVERED: To determine the safety of RCI in the treatment of RA, adverse events (AEs) from a recent clinical trial of RCI as an adjunctive therapy along with DMARDs and glucocorticoids (ClinicalTrials.gov identifier NCT02919761) were compared with AEs reported in randomized clinical trials of DMARDs and glucocorticoids alone. A systematic review of the literature yielded 4 articles describing the detailed safety results of DMARD/glucocorticoid combination therapy used in the treatment of RA for comparison. EXPERT OPINION: There were no clinically significant differences between the AE profiles of RCI/DMARD/glucocorticoid treatment in the RCI clinical trial and those in the DMARD/glucocorticoid safety profile compiled from the reviewed clinical trials; this was supported by pharmacovigilance data. These results support the short-term safety of RCI as an adjunctive therapy for patients with persistently active RA.

14.
Rheumatol Ther ; 7(2): 327-344, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32185745

RESUMO

INTRODUCTION: The objective of this study was to assess efficacy and safety of repository corticotropin injection (RCI) in subjects with active rheumatoid arthritis (RA) despite treatment with a corticosteroid and one or two disease-modifying antirheumatic drugs (DMARDs). METHODS: All subjects received open-label RCI (80 U) twice weekly for 12 weeks (part 1); only those with low disease activity [LDA; i.e., Disease Activity Score 28 joint count and erythrocyte sedimentation rate (DAS28-ESR) < 3.2] were randomly assigned to receive either RCI (80 U) or placebo twice weekly during the 12-week double-blind period (part 2). The primary efficacy endpoint was the proportion of subjects who achieved LDA at week 12. Secondary efficacy endpoints included proportions of subjects who maintained LDA during weeks 12 through 24 and achieved Clinical Disease Activity Index (CDAI) ≤ 10 at weeks 12 and 24. Safety was assessed via adverse event reports. RESULTS: Of the 259 enrolled subjects, 235 completed part 1; 154 subjects (n = 77 each for RCI and placebo) entered part 2, and 127 (RCI, n = 71; placebo, n = 56) completed. At week 12, 163 subjects (62.9%) achieved LDA and 169 (65.3%) achieved CDAI ≤ 10 (both p < 0.0001). At week 24, 47 (61.0%) RCI-treated and 32 (42.1%) placebo-treated subjects maintained LDA (p = 0.019); 66 (85.7%) RCI-treated and 50 (65.8%) placebo-treated subjects maintained CDAI ≤ 10 (p = 0.004). No unexpected safety signals were observed. CONCLUSIONS: RCI was effective and generally safe in patients with active RA despite corticosteroid/DMARD therapy. By week 12, > 60% of patients achieved LDA, which was maintained with 12 additional weeks of treatment. Most patients who achieved LDA maintained it for 3 months after RCI discontinuation. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT02919761.

15.
Rheumatology (Oxford) ; 59(10): 2774-2784, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32031665

RESUMO

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 naïve 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. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01695239, EudraCT 2011-002326-49.

18.
Rheumatol Ther ; 7(1): 35-64, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31950442

RESUMO

The act of nonmedical switching, defined as switching stable patients who are generally doing well with their current therapy from an originator biologic to its biosimilar, has been endorsed as a reasonable treatment strategy. The safety and efficacy of nonmedical switching have been evaluated in randomized controlled and real-world evidence studies, which have demonstrated that although many patients maintain treatment response after the switch, some patients experience therapy failure, resulting in therapy discontinuation. It has been postulated that the vast majority, if not all, of these treatment failures result from a "nocebo effect", defined as patients' negative expectations toward the therapy change. Reports suggest that the risk of a nocebo effect is higher following a mandated nonmedical switch. Although the nocebo effect is a well-recognized phenomenon in pain studies, evidence is limited in immune-mediated diseases primarily because it is difficult to quantify, especially retrospectively. In spite of this, numerous biosimilar studies in patients with immune-mediated diseases have concluded that nonmedical switching failures are due to a nocebo effect. The objective of this narrative review was to explore the reasons for nonmedical switch failure or discontinuation and the role of the nocebo effect among patients with inflammatory rheumatic and gastrointestinal diseases who switched from an originator biologic to its biosimilar.

19.
Clin Exp Rheumatol ; 38(5): 848-857, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31858963

RESUMO

OBJECTIVES: Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Here we present data from the completed Phase 3 randomised controlled trial (RCT) ORAL Scan (NCT00847613), which evaluated the impact of tofacitinib on patient-reported outcomes (PROs) through 24 months in patients with active RA and inadequate responses to methotrexate (MTX-IR). METHODS: Patients were randomised 4:4:1:1 to receive tofacitinib 5 or 10 mg twice daily (BID), or placebo advanced to tofacitinib 5 or 10 mg, plus background MTX. Patients receiving placebo advanced to tofacitinib at month 3 (non-responders) or month 6 (remaining patients). Mean changes from baseline in PROs, assessed at months 1-24, included Health Assessment Questionnaire-Disability Index, Patient Global Assessment of disease activity (visual analogue scale [VAS]), Patient Assessment of Arthritis Pain (VAS), health-related quality of life (Short Form-36 version 2), Functional Assessment of Chronic Illness Therapy-Fatigue and Medical Outcomes Study-Sleep. RESULTS: Overall, 539/797 (67.6%) patients completed 24 months' treatment. At month 3, tofacitinib-treated patients reported signi cant (p<0.05) mean changes from baseline versus placebo across all PROs, and significantly more patients reported improvements ≥ minimum clinically important differences versus placebo. Improvements in PROs with tofacitinib were sustained to month 24. Following advancement to tofacitinib, placebo-treated patients generally reported changes of similar magnitude to tofacitinib-treated patients. CONCLUSIONS: Patients with RA and MTX-IR receiving tofacitinib 5 or 10 mg BID plus MTX reported significant and clinically meaningful improvements in PROs versus placebo at month 3, which were sustained through 24 months.


Assuntos
Antirreumáticos , Artrite Reumatoide , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Metotrexato/uso terapêutico , Medidas de Resultados Relatados pelo Paciente , Piperidinas , Pirimidinas , Pirróis/uso terapêutico , Resultado do Tratamento
20.
Rheumatol Ther ; 7(1): 1-3, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31823213
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