Previous Tumour Necrosis Factor Inhibitor Research Articles

Matching-Adjusted Indirect Comparison of the 52-Week Efficacy of Bimekizumab Versus Secukinumab and Ixekizumab for the Treatment of Radiographic Axial Spondyloarthritis.

A previous network meta-analysis established 16-week relative efficacy with bimekizumab, an inhibitor of interleukin (IL)-17F in addition to IL-17A, versus other treatments for patients with radiographic axial spondyloarthritis (r-axSpA; i.e., ankylosing spondylitis), including the IL-17A inhibitors secukinumab and ixekizumab. This matching-adjusted indirect comparison (MAIC) assessed 52-week relative efficacy of bimekizumab versus secukinumab and ixekizumab. Individual patient data from BE MOBILE 2 (bimekizumab 160mg; N = 220) were matched to pooled summary data from MEASURE 1/2/3/4 (secukinumab 150mg), MEASURE 3 (secukinumab 300mg; escalated dose for inadequate responders), COAST-V (ixekizumab) and COAST-V/-W (ixekizumab). BE MOBILE 2 patients were reweighted using propensity score weights based on age, sex, ethnicity, tumor necrosis factor inhibitor (TNFi) exposure, weight, baseline ASDAS and BASFI (secukinumab) and baseline BASDAI (ixekizumab), and 52-week efficacy outcomes from the trial recalculated. Odds ratios (OR) or mean difference for unanchored comparisons are reported with 95% confidence intervals (CI). At week 52, MAIC demonstrated that patients may have higher likelihood of improvement in key efficacy outcomes with bimekizumab versus secukinumab 150mg (e.g., ASAS40: [OR (95% CI): 1.48 (1.05, 2.10); p = 0.026]; effective sample size [ESS] = 177). Differences in 52-week efficacy outcomes between bimekizumab and secukinumab 300mg dose escalation were non-significant (ESS = 120). Bimekizumab versus ixekizumab 80mg comparisons (COAST-V only; ESS = 84) also suggested that differences were non-significant for most key efficacy outcomes. Other ixekizumab comparisons (COAST-V/-W; ESS = 45) suggested bimekizumab may have higher comparative efficacy for many of the same efficacy outcomes, however ixekizumab analyses were limited by poor population overlap, likely due to the greater proportion of patients with previous TNFi exposure. Patients treated with bimekizumab may have a higher likelihood of achieving improved longer-term efficacy versus secukinumab 150mg, suggesting bimekizumab may be a favorable therapeutic option for r-axSpA. Differences in efficacy outcomes with bimekizumab versus ixekizumab 80mg were mostly non-significant, depending on the populations considered.

P877 A comparison of vedolizumab and ustekinumab treatment in patients with Ulcerative Colitis after failure of treatment with tumor necrosis factor inhibitor

Abstract Background Data comparing vedolizumab (VDZ) and ustekinumab (UST) in patients with ulcerative colitis (UC) previously treated with tumor necrosis factor inhibitor (TNFi) and followed with regular serum-drug measurements are scarce. In the national pharmaceutical tender system of Norway, VDZ was listed as the first drug of choice after failed TNFi treatment from 2016 to 2019 and UST from 2020 to 2022. We aimed to compare drug persistence, effectiveness, drug dosing and disease activity in patients treated with VDZ or UST after failed TNFi therapy. Methods We included patients who had failed at least one TNFi and started either VDZ treatment (years 2016-2019) or UST (years 2020-2022). Patients were followed for one year after initiating the treatment or until discontinuation. Prospectively recorded data were obtained from the electronic patient journal (EPJ) and the local IBD-registry. Clinical remission was defined as 6-point Mayo Score ≤1, and biochemical remission was defined as CRP<5 mg/L and FC<250 µg/g. Patients were followed with regular serum-drug measurements and dose adjustments were made at the discretion of the treating physician based on serum-drug measurements and clinical activity at follow-up visits. Wilcoxon signed rank and Mann Whitney U test were used to assess differences in paired and unpaired data, respectively. Results A total of 116 patients were included, 59 treated with VDZ and 57 with UST. At 52 weeks, there was no difference in estimated drug persistence with 85% [73-92] for VDZ and 92% [80-96] for UST. Clinical remission increased significantly in both groups (Table 1), and no difference was found between UST and VDZ for clinical remission at week 0 and 52 (OR=2.1 [0.9-4.5] and OR=0.9 [0.3-2.3]). Contrary to the VDZ group, there was a significant decrease in CRP from week 0 to 52 in the UST group, while FC decreased significantly in both groups (Table 1). The proportion of patients in biochemical remission increased in the UST group while there was no significant change in the VDZ group. Significantly more patients treated with UST received an intensified treatment regime at 52 weeks (interval less than eight weeks) compared to VDZ treated patients (87% (95% CI [74-94]) vs 59% (95% CI [45-72])). Conclusion This study demonstrates that one-year drug persistence and clinical remission were high and comparable in both UST and VDZ treated UC patients with previous TNFi failure. Treatment with UST, but not VDZ, was associated with a significant increase in the proportion of patients in biochemical remission from induction to 52 weeks. However, a significantly larger proportion of patients treated with UST received intensified dosing at 52 weeks compared with VDZ treated patients.

OP0258 IZOKIBEP (ABY-035) IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS – 16-WEEK RESULTS FROM A PHASE 2 STUDY

BackgroundPsoriatic arthritis (PsA) is a chronic, immune-mediated inflammatory disease with heterogenous musculoskeletal manifestation (arthritis, spondylitis, enthesitis, dactylitis) and extra-musculoskeletal manifestation (skin and nail psoriasis). In addition, PsA is commonly associated with comorbidities such as metabolic syndrome and cardiovascular diseases where IL-17 is a key driver of this disease.Izokibep is a unique IL-17A inhibitor with extraordinary potency and small molecular size designed to overcome the limitations of monoclonal antibodies such as poor tissue distribution.Here, we report 16-week phase 2 results in patients with active PsA.ObjectivesTo assess efficacy, safety, pharmacokinetics and immunogenicity of izokibep versus placebo.MethodsThis is a prospective, multicenter, randomized, double-blind, placebo-controlled, parallel-groups, dose-finding trial studying bi-weekly 80 mg or 40 mg izokibep administered subcutaneously versus placebo until Week 16 (Period 1) and dose-controlled treatment until Week 46 (Period 2). PsA patients had to have ≥3 swollen and ≥3 tender joints of the 66/68 joint count, and an inadequate response to previous NSAIDs, csDMARDs or TNF inhibitor therapy. The primary endpoint was to evaluate ACR50 responses of 80 mg bi-weekly versus placebo at Week 16. Key secondary endpoints were ACR20/70, MDA, DAS28, DAPSA, SPARCC, LDI, PASI as well as tolerability and safety. Efficacy outcome measures were assessed in all patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT04713072.Results135 patients were randomized and treated between June 2020 and July 2021 in 22 European sites located in Austria, Belgium, Czech Republic, Germany, Hungary, Poland and Spain.At baseline, patients had a mean age of 48.5 (SD 12.0) years, a mean BMI of 29.0 (SD 4.8) kg/m2, a mean swollen joint count (SJC) of 9.9 (SD 6.6), and a mean tender joint count (TJC) of 16.7 (SD 10.4). The mean PsA disease duration was 7.1 (SD 7.8) years. 13% failed previous TNF inhibitor treatment and 80% received a concomitant csDMARD.At Week 16, the confirmatory primary endpoint ACR50 response rate was met (p=0.0003). ACR50 response rate was 52% in the 80 mg group, 48% in the 40 mg and 13% in the placebo group. The ACR20/50/70 response rates up to Week 16 by treatment group are presented in Figure 1.Figure 1.ACR20/50/70 response ratesSJC and TJC rapidly decreased with active treatment as indicated in Table 1.Table 1.SJC and TJC by visit until Week 16Mean SJC (SD)Mean TJC (SD)Study WeekPlacebo Q2W N=4440 mg Q2WN=4480 mg Q2WN=47Placebo Q2WN=4440 mg Q2WN=4480 mg Q2WN=47BL9.2 (6.4)10.1 (7.0)10.4 (6.4)16.4 (11.3)16.7 (10.3)17.0 (9.7)28.4 (6.1)7.3 (6.5)7.6 (7.6)14.9 (10.0)13.3 (9.5)13.8 (10.7)47.7 (7.7)6.0 (7.0)5.6 (6.2)14.1 (11.8)12.5 (11.6)11.2 (9.2)86.0 (6.2)3.5 (4.1)3.7 (4.7)10.5 (7.5)9.0 (10.5)7.4 (7.2)125.1 (5.2)2.6 (3.4)2.3 (3.4)10.9 (8.7)8.1 (8.9)6.0 (6.7)165.0 (5.7)2.4 (3.7)1.7 (2.7)10.7 (9.1)7.1 (7.7)5.6 (6.8)There was a dose-response relationship and a fast onset of response.No serious or severe adverse events occurred during Period 1. The three most frequently affected System Organ Classes (SOCs) were SOC General disorders and administration site conditions comprising mainly mild injection site reactions or erythema followed by SOC Infections and infestations and SOC Metabolism and nutrition disorders. One mild, transient vulvovaginal Candida infection with active treatment was reported. Apart from injection site reactions there were no apparent differences in the occurrence of adverse events between active and placebo patients.ConclusionIn this phase 2 study, izokibep showed a dose-dependent high degree of efficacy in patients with active PsA having failed previous treatment. Overall, izokibep was well tolerated.These data strongly support further clinical development.ReferencesNoneAcknowledgementsAffibody AB, Sweden, and ACELYRIN Inc, USA, funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of this publication. All authors participated in the drafting, review, and approval of this publication.Disclosure of InterestsFrank Behrens Shareholder of: Pfizer, Sanofi, GlaxoSmithKline, Gilead Sciences, Inc., Novartis, Speakers bureau: Amgen, Horizon, Lilly, Novartis, Pfizer, Sanofi, Genzyme, Flexion, AbbVie, Consultant of: AbbVie, Boehringer Ingelheim, Flexion, Janssen, Pfizer, Sanofi, Regeneron, SUN Pharma Advanced Research, Gilead Sciences, Inc., Grant/research support from: Pfizer, Janssen, Chugai, Celgene, Roche, Alan Kivitz, Peter C. Taylor Consultant of: AbbVie, Biogen, Bristol Myers Squibb, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Nordic Pharma, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: Celgene and Galapagos, Dieter Wetzel Consultant of: Acino, Affibody, Biotest, Cheplapharm, CSL Behring, Mundipharma, Roche, Sandoz, Temmler, Nikolai C Brun Employee of: Affibody AB, Jan Brandt-Juergens Speakers bureau: Abbvie, Pfizer, Roche, Sanofi-Aventis, Novartis, Lilly, MSD, UCB, BMS, Janssen, Medac, Gilead, Affibody, Paid instructor for: Abbvie, Pfizer, Roche, Sanofi-Aventis, Novartis, Lilly, MSD, UCB, BMS, Janssen, Medac, Gilead, Affibody, Edit Drescher: None declared, Eva Dokoupilova: None declared, Anna Rowińska-Osuch: None declared, Nadia Abdel-Kader Martin Speakers bureau: Pfizer in 2011, Kurt de Vlam Speakers bureau: AbbVie, Amgen, Eli Lilly, Novartis, UCB, Paid instructor for: Amgen, Galapagos, UCB, Consultant of: Eli Lilly, Johnson &Johnson, Novartis Galapagos, UCB, Grant/research support from: Celgene

Comparison of long-term efficacy between biological agents following tumor necrosis factor inhibitor failure in patients with rheumatoid arthritis: a prospective cohort study.

Background:Currently, there is contradictory evidence regarding the best strategy to follow after discontinuation of a first biological agent in patients with rheumatoid arthritis (RA). We aimed to compare the long-term efficacy of switching to a second tumor necrosis factor inhibitor (TNFi) versus biopharmaceuticals with other mechanisms of action (non-TNFi) in patients with RA who previously failed a first TNFi.Methods:This prospective cohort study analyzed data from 127 patients who discontinued a previous TNFi between 1999 and 2016. Disease activity was assessed at baseline and at 6, 12, and 24 months (m-6, m-12, m-24) after switching. Primary outcome was the proportion of patients achieving good/moderate EULAR response (E-resp). Factors associated with clinical outcomes were assessed using univariate and multivariate logistic regression models.Results:Seventy-seven (61%) patients received a second TNFi and 50 (39%) switched to a non-TNFi. At m-6 and m-12, no differences were observed between groups; nevertheless, at m-24, the proportion of patients with E-resp was higher in the non-TNFi group (49% TNFi group versus 77% non-TNFi group; p = 0.002). In regression models, switching to a non-TNFi was significantly associated with E-resp at m-24 (odds ratio = 3.21; p = 0.01). When assessing the response to the second biological agent based on the reason for discontinuation of the first TNFi, similar results were obtained; at m-24, patients who discontinued the first TNFi due to inefficacy (either primary or secondary) experienced a better E-resp if they had switched to a non-TNFi (primary inefficacy: 52% TNFi group versus 79% non-TNFi group, p = 0.09; secondary inefficacy: 50% versus 76%, p = 0.03).Conclusion:In our cohort of RA patients who discontinued a first TNFi, those who switched to a non-TNFi were three times more likely to attain a sustained clinical response, regardless of whether they had discontinued the first biologic due to a primary or secondary inefficacy.

Cobitolimod for moderate-to-severe, left-sided ulcerative colitis (CONDUCT): a phase 2b randomised, double-blind, placebo-controlled, dose-ranging induction trial

Cobitolimod is a topically administered, DNA-based oligonucleotide that activates Toll-like receptor 9 (TLR9), and previous research has shown clinical efficacy in patients with moderate-to-severe ulcerative colitis. Here we assessed the efficacy and safety of different dose regimens of cobitolimod for induction therapy in patients with moderate-to-severe, left-sided ulcerative colitis. CONDUCT was a randomised, double-blind, five-arm, placebo-controlled, dose-ranging phase 2b study that recruited patients with moderate-to-severe, left-sided ulcerative colitis, with inadequate response to conventional or biological therapies, from 91 hospitals or outpatient clinics in 12 European countries. Eligible patients had a Mayo score of 6-12 with a centrally read endoscopic subscore (modified to exclude friability from grade 1) of 2 or higher and no individual subscore of less than 1, and confirmation of left-sided disease. Patients were randomised (1:1:1:1:1; block size of ten) via a computer-generated schedule and centralised interactive voice and web response system to receive rectal enemas of cobitolimod at 31 mg, 125 mg, or 250 mg at weeks 0 and 3 (2 × 31 mg, 2 × 125 mg, and 2 × 250 mg groups), cobitolimod at 125 mg at weeks 0, 1, 2, and 3 (4 × 125 mg group), or placebo. Randomisation was stratified by current glucocorticosteroid and previous tumour necrosis factor inhibitor treatment. Patients and all study personnel were masked to treatment allocation. The primary endpoint was the proportion of patients achieving clinical remission (Mayo subscores for rectal bleeding of 0, for stool frequency of 0 or 1 [with ≥1-point decrease from baseline], and for endoscopy of 0 or 1 [excluding friability]) at week 6. The primary analysis (based on intention to treat) and safety analysis were done in all randomly assigned patients who received at least one dose of active study drug or placebo. In this exploratory study, statistical tests were one-sided; p values of less than 0·10 were regarded as statistically significant, with no adjustment for multiplicity. This study is registered with ClinicalTrials.gov, NCT03178669, and is completed; the results here represent the final analysis. 213 patients were randomly assigned between June 30, 2017, and June 26, 2019. Of these, 211 patients received study treatment: 40 in the cobitolimod 2 × 31 mg group, 43 in the 2 × 125 mg group, 42 in the 4 × 125 mg group, 42 in the 2 × 250 mg group, and 44 in the placebo group. A greater proportion of patients were in clinical remission at week 6 in the cobitolimod 2 × 250 mg group than in the placebo group (nine [21%] of 42 patients vs three [7%] of 44; odds ratio [OR] 3·8 [80% CI 1·5-9·5]; one-sided p=0·025). We identified no significant difference in the proportion of patients with clinical remission in the cobitolimod 2 × 31 mg group (five [13%] of 40 patients; OR 2·0 [80% CI 0·7-5·5], p=0·18), 2 × 125 mg group (two [5%] of 43; 0·7 [0·2-2·2], p=0·66), or 4 × 125 mg (four [10%] of 42; 1·4 [0·5-3·9], p=0·33) compared with the placebo group. Treatment-emergent adverse events occurred in 21 (48%) patients in the placebo group, ten (25%) patients in the cobitolimod 2 × 31 mg group, 17 (40%) patients in the 2 × 125 mg group, 15 (36%) patients in the 4 × 125 mg group, and 18 (43%) patients in the 2 × 250 mg group. Severe adverse events occurred in eight (4%) of 211 patients (worsening of ulcerative colitis [seven patients] and abdominal hernia and wound dehiscence [one patient]). Ten patients (two [5%] in the placebo group, two [5%] in the cobitolimod 2 × 31 mg group, two [5%] in the 4 × 125 mg, and four [10%] in the 2 × 250 mg group) had a total of 13 serious adverse events; these were worsening of ulcerative colitis (eight events) and pruritus, rash, abdominal hernia, fascia dehiscence, and deep vein thrombosis (one event each). One patient in the placebo group died from total organ failure after receiving a colectomy for a serious adverse event of disease worsening. Two topical administrations of cobitolimod 250 mg were well tolerated and more effective than placebo in inducing clinical remission 6 weeks after the start of treatment. TLR9 activation is a promising novel therapeutic target in ulcerative colitis and warrants further testing, with phase 3 trials of cobitolimod planned. InDex Pharmaceuticals.

Non-TNF inhibitor switchers versus TNF inhibitor cyclers from multicentre rheumatoid arthritis ultrasonography prospective cohort in Japan

To compare therapeutic efficacy of tumour necrosis factor inhibitor (TNFi) cyclers and non-TNFi switchers in patients with rheumatoid arthritis (RA) having inadequate response to previous TNFis (TNF-IR patients) using composite measures including imaging assessment with power Doppler ultrasonography (PDUS). Patients with RA who had inadequate response to one or more previous TNFi agents with moderate or higher disease activity were enrolled. The outcomes of 56 TNF-IR patients were analysed. Patients were divided into 19 TNFi cyclers and 37 non-TNFi switchers (16 abatacept [ABT] and 21 tocilizumab [TCZ] switchers). Retention ratio at 6 months was significantly higher in non-TNFi switchers than in TNFi cyclers (p < .05). Although there was no significant difference, non-TNFi switchers tended to have a larger decrease than TNFi cyclers in efficacy indicators based on clinical disease activity index and PDUS. Multivariate logistic regression analysis identified a following independent factor associated with both EULAR good response and retention of a biologic agent: non-TNFi switch (p < .05 for both). Non-TNFi switchers were shown to have significantly higher percentage of EULAR good response and higher retention than TNFi cyclers. A non-TNFi biologic agent may hence be a preferential next-line treatment for TNF-IR patients.

Risankizumab compared with adalimumab in patients with moderate-to-severe plaque psoriasis (IMMvent): a randomised, double-blind, active-comparator-controlled phase 3 trial

Psoriasis is an autoimmune disease that affects approximately 100 million people worldwide, and is a disease that can be ameliorated by anti-cytokine treatment. We aimed to compare the efficacy and safety of risankizumab with adalimumab in patients with moderate-to-severe plaque psoriasis. IMMvent was a phase 3, randomised, double-blind, active-comparator-controlled trial completed at 66 clinics in 11 countries. Eligible patients were aged 18 years or older with moderate-to-severe chronic plaque psoriasis. Patients were randomly assigned 1:1 using interactive response technology to receive 150 mg risankizumab subcutaneously at weeks 0 and 4 or 80 mg adalimumab subcutaneously at randomisation, then 40 mg at weeks 1, 3, 5, and every other week thereafter during a 16-week double-blind treatment period (part A). For weeks 16-44 (part B), adalimumab intermediate responders were re-randomised 1:1 to continue 40 mg adalimumab or switch to 150 mg risankizumab. In part A, participants and investigators were masked to study treatment. Randomisation was stratified by weight and previous tumour necrosis factor inhibitor exposure. Co-primary endpoints in part A were a 90% improvement from baseline (PASI 90) and a static Physician's Global Assessment (sPGA) score of 0 or 1 at week 16, and for part B was PASI 90 at week 44 (non-responder imputation). Efficacy analyses were done in the intention-to-treat population and safety analyses were done in the safety population (all patients who received at least one dose of study drug or placebo). This study is registered with ClinicalTrials.gov, number NCT02694523. Between March 31, 2016, and Aug 24, 2017, 605 patients were randomly assigned to receive either risankizumab (n=301, 50%) or adalimumab (n=304, 50%). 294 (98%) of patients in the risankizumab group and 291 (96%) in the adalimumab group completed part A, and 51 (96%) of 53 patients re-randomised to risankizumab and 51 (91%) of 56 patients re-randomised to continue adalimumab completed part B. At week 16, PASI 90 was achieved in 218 (72%) of 301 patients given risankizumab and 144 (47%) of 304 patients given adalimumab (adjusted absolute difference 24·9% [95% CI 17·5-32·4]; p<0·0001), and sPGA scores of 0 or 1 were achieved in 252 (84%) patients given risankizumab and 252 (60%) patients given adalimumab (adjusted absolute difference 23·3% [16·6-30·1]; p<0·0001). In part B, among adalimumab intermediate responders, PASI 90 was achieved by 35 (66%) of 53 patients switched to risankizumab and 12 (21%) of 56 patients continuing adalimumab (adjusted absolute difference 45·0% [28·9-61·1]; p<0·0001) at week 44. Adverse events were reported in 168 (56%) of 301 patients given risankizumab and 179 (57%) of 304 patients given adalimumab in part A, and among adalimumab intermediate responders, adverse events were reported in 40 (75%) of 53 patients who switched to risankizumab and 37 (66%) of 56 patients who continued adalimumab in part B. Risankizumab showed significantly greater efficacy than adalimumab in providing skin clearance in patients with moderate-to-severe plaque psoriasis. No additional safety concerns were identified for patients who switched from adalimumab to risankizumab. Treatment with risankizumab provides flexibility in the long-term treatment of psoriasis. AbbVie and Boehringer Ingelheim.

Comparative effectiveness of secukinumab and adalimumab in ankylosing spondylitis as assessed by matching-adjusted indirect comparison.

ObjectiveMatching-adjusted indirect comparison was used to assess the comparative effectiveness of secukinumab 150 mg and adalimumab 40 mg in biologic-naïve patients with ankylosing spondylitis (AS) for up to 1 year.MethodsPooled individual patient data from the secukinumab arms of MEASURE 1 (NCT01358175) and MEASURE 2 (NCT01649375) trials (n=197) were matched against the ATLAS (NCT00085644) adalimumab population (n=208). Logistic regression analysis was used to determined weights to match for age, sex, Bath AS Functional Index, C-reactive protein levels, and previous tumor necrosis factor inhibitor therapy. Recalculated Assessment of SpondyloArthritis International Society (ASAS) 20 and 40 responses at weeks 8, 12, 16, 24, and 52 from MEASURE 1/2 (effective sample size=120) were compared with those of ATLAS. Anchored (placebo-adjusted) comparisons were possible until week 12, and unanchored (non-placebo-adjusted) comparisons were necessary thereafter.ResultsFor placebo-anchored ASAS 20 and 40 comparisons up to week 12, there were no differences between secukinumab and adalimumab. For unanchored comparisons at week 16, ASAS 20 was higher for secukinumab [odds ratio 1.60 (95% confidence interval, 1.01–2.54); p=0.047]; at week 24, ASAS 20 and 40 were higher for secukinumab [1.76 (1.11–2.79); p=0.017 and 1.79 (1.14–2.82); p=0.012, respectively]; and at week 52, ASAS 40 was higher for secukinumab [1.54 (1.06–2.23); p=0.023] than for adalimumab.ConclusionThere were no differences observed in placebo-adjusted ASAS 20 and 40 responses up to 12 weeks between secukinumab- and adalimumab-treated patients with ankylosing spondylitis. After week 12, secukinumab demonstrated signs of greater improvement in non-placebo-adjusted ASAS 20 and 40 responses than adalimumab.

Ixekizumab is efficacious when used alone or when added to conventional synthetic disease-modifying antirheumatic drugs (cDMARDs) in patients with active psoriatic arthritis and previous inadequate response or intolerance to tumour necrosis factor inhibitors

ObjectiveTo conduct subset analyses of SPIRIT-P2 (NCT02349295) to investigate the efficacy and safety of ixekizumab versus placebo in three subgroups of patients with active psoriatic arthritis (PsA) according to the...

Switching biologics in the treatment of psoriatic arthritis.

Psoriatic arthritis (PsA) is a heterogeneous inflammatory disorder that requires targeted treatment based on clinical manifestations, symptom severity, comorbidities, and other factors. Moderate or severe peripheral arthritis symptoms are typically treated with disease-modifying antirheumatic drugs (DMARDs) or biologic DMARDs (bDMARDs), and early and aggressive treatment is recommended in order to prevent permanent damage. Although rheumatologists are now able to choose between several bDMARDs for PsA that have different chemical structures, pharmacokinetic properties, dosing regimens, immunogenicity, safety profiles, and mechanisms of action, there is a lack of typical patient profiles or detailed treatment algorithms that can be followed when patients require alterations in their therapeutic regimens. PsA treatment recommendations were evaluated to identify consensus guidelines on switching between bDMARD therapies. PubMed literature searches were then conducted using the terms psoriatic arthritis, switch/switching, biologic, and TNF/tumor necrosis factor. Articles were deemed relevant if they presented data on switching between different bDMARDs in patients with PsA. Data from the clinical literature on switching bDMARD therapies in PsA are limited. Evidence suggests that response to adalimumab, etanercept, and ustekinumab is lower after previous tumor necrosis factor inhibitor (TNFi) therapy and the efficacy of infliximab is independent of previous bDMARD treatment. Trials of ustekinumab and secukinumab showed efficacy responses were greater compared with placebo in patients who failed to respond to ≥1 TNFi. Switching bDMARD therapies is a recommended strategy for patients who experience treatment failure. Many factors must be considered for determining which agent to switch to including PsA disease characteristics, comorbidities, cardiometabolic risk factors, treatment history, and patient preference. Switching between TNFis can be effective for many patients, but bDMARDs with different mechanisms of action may be superior alternatives.

Differential effects of IL-6 blockade tocilizumab and TNF inhibitors on angiogenesis in synovial tissues from patients with rheumatoid arthritis

Objective: To compare the influences of tocilizumab (TCZ) and TNF inhibitors (TNFi) on the angiogenesis in synovial tissues of rheumatoid arthritis (RA).Methods: Synovial tissues were obtained during joint operations from 13 RA patients treated with TCZ for at least 4 months with or without previous use of TNFi, from 13 RA patients with TNFi alone and from 10 RA patients with only conventional synthetic DMARDs (csDMARDs). Synovial tissues were evaluated by hematoxylin and eosin stain as well as by immunohistological staining with anti-CD31 in which the microvessel densities (MVD) were quantitated. Synovial histopathology was scored for various components.Results: The most remarkable change in the synovium with TCZ was reduced angiogenesis as well as degeneration of lining layers irrespective of the previous use of TNFi. Thus, MVD in patients treated with TCZ with or without previous TNFi were significantly decreased compared with those in patients with TNFi alone or with csDMARDs. Moreover, MVD was significantly correlated with lining layer proliferation, but not with synovial stromal proliferation or inflammatory changes.Conclusions: These results demonstrated that inhibition of angiogenesis is a unique action of TCZ. Moreover, the data also suggest that lining layers proliferation might be closely associated with angiogenesis.

Effectiveness and survival-on-drug of certolizumab pegol in rheumatoid arthritis in clinical practice: results from the national Swedish register

Objectives: Evidence regarding the efficacy and effectiveness of certolizumab pegol (CZP) in rheumatoid arthritis (RA) patients who have failed to respond to treatment with a tumour necrosis factor inhibitor (TNFi) is limited. The aim of this study was to describe the effectiveness and survival-on-drug of CZP in a real-life setting, both in TNFi-naïve patients and in patients who had previously failed TNFis, and in relation to disease activity at baseline.Method: The national Swedish Rheumatology Quality Register (SRQ) was used to identify patients with RA starting treatment with CZP between 2009 and 2013. The effectiveness of treatment was assessed using the 28-joint Disease Activity Score (DAS28), the Health Assessment Questionnaire (HAQ), measures of remission, the European League Against Rheumatism (EULAR) response during 0–6 months from start of treatment, and survival-on-drug during the first 30 months.Results: A total of 945 RA patients started treatment with CZP. Of these, 540 (57.1%) received CZP as the first biological treatment, 215 (23%) had failed one previous TNFi, and 190 (20%) had failed at least two TNFis. Overall, 71% achieved at least a EULAR moderate response and 38% had a EULAR good response at 6 months from baseline. TNFi-naïve patients achieved significantly better results and had better survival-on-drug compared to patients who had failed previous TNFis. Around 20% of patients who had not responded to two or more prior TNFis achieved EULAR good response to therapy and a similar percentage achieved remission. Patients who had high baseline disease activity had a higher risk of discontinuing treatment compared to those without high disease activity.Conclusions: In this real-life RA cohort, CZP was associated with significant clinical improvement. The effectiveness and survival-on-drug vary markedly depending on the line of treatment.

Cost-effectiveness of abatacept, rituximab, and TNFi treatment after previous failure with TNFi treatment in rheumatoid arthritis: a pragmatic multi-centre randomised trial.

IntroductionFor patients with rheumatoid arthritis (RA) whose treatment with a tumour necrosis factor inhibitor (TNFi) is failing, several biological treatment options are available. Often, another TNFi or a biological with another mode of action is prescribed. The objective of this study was to compare the effectiveness and cost-effectiveness of three biologic treatments with different modes of action in patients with RA whose TNFi therapy is failing.MethodsWe conducted a pragmatic, 1-year randomised trial in a multicentre setting. Patients with active RA despite previous TNFi treatment were randomised to receive abatacept, rituximab or a different TNFi. The primary outcome (Disease Activity Score in 28 joints) and the secondary outcomes (Health Assessment Questionnaire Disability Index and 36-item Short Form Health Survey scores) were analysed using linear mixed models. Cost-effectiveness was analysed on the basis of incremental net monetary benefit, which was based on quality-adjusted life-years (calculated using EQ-5D scores), and all medication expenditures consumed in 1 year. All analyses were also corrected for possible confounders.ResultsOf 144 randomised patients, 5 were excluded and 139 started taking abatacept (43 patients), rituximab (46 patients) or a different TNFi (50 patients). There were no significant differences between the three groups with respect to multiple measures of RA outcomes. However, our analysis revealed that rituximab therapy is significantly more cost-effective than both abatacept and TNFi over a willingness-to-pay range of 0 to 80,000 euros.ConclusionsAll three treatment options were similarly effective; however, when costs were factored into the treatment decision, rituximab was the best option available to patients whose first TNFi treatment failed. However, generalization of these costs to other countries should be undertaken carefully.Trial registrationNetherlands Trial Register number NTR1605. Registered 24 December 2008.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0630-5) contains supplementary material, which is available to authorized users.

FRI0295 Rituximab Retention Rate in Clinical Practice: A Large Multicentre Italian Cohort of Rheumatoid Arthritis Patients

BackgroundRituximab (RTX), a chimeric monoclonal antibody targeting CD20 B cell antigens, is a safe and effective treatment for rheumatoid arthritis (RA) [1]. It has been approved for RA patients who...

Safety of resuming tumour necrosis factor inhibitors in patients who developed tuberculosis as a complication of previous TNF inhibitors

There is no consensus on whether restarting TNF inhibitors (TNFis) after treatment of an active tuberculosis (TB) infection caused by previous TNFi exposure is safe. In this study we sought to determine the safety of resuming TNFis in patients following TB treatment. The medical records of all patients (n = 683) that received TNFi treatment at a single rheumatology clinic between June 2003 and December 2012 were retrospectively reviewed. Among them, data from patients who developed active TB infection were collected and patient outcomes were evaluated for those who resumed TNFis after TB treatment. Of 683 patients, 13 patients developed an active TB infection during TNFi treatment (4 on etanercept, 4 on adalimumab and 5 on infliximab). The median duration of TNFi treatment before TB infection was 20 months. TNFi treatment was reinitiated in six patients: four within 2 months after TB treatment and two after completion of TB treatment. Four patients reinitiated with the same TNFi, whereas two patients started with another TNFi. During a mean follow-up of 30.6 months, all six patients successfully completed TB treatment with no TB infection relapses. Our results suggest that resuming TNFi therapy in patients following adequate TB treatment is safe, even before completion of TB treatment.

Rituximab versus an alternative TNF inhibitor in patients with rheumatoid arthritis who failed to respond to a single previous TNF inhibitor: SWITCH-RA, a global, observational, comparative effectiveness study

ObjectivesTo compare the effectiveness of rituximab versus an alternative tumour necrosis factor (TNF) inhibitor (TNFi) in patients with rheumatoid arthritis (RA) with an inadequate response to one previous TNFi.MethodsSWITCH-RA was...

Monitoring C-reactive protein levels to predict favourable clinical outcomes from tocilizumab treatment in patients with rheumatoid arthritis

Objectives The inflammatory cytokine interleukin-6 (IL-6) directly stimulates C-reactive protein (CRP) expression. The present study aimed to examine how clinical treatment outcomes of rheumatoid arthritis (RA) with tocilizumab (TCZ), a humanised monoclonal anti-IL-6 receptor antibody, are related to CRP levels monitored for 52 weeks.Methods One hundred and twenty-two RA patients who underwent TCZ treatment between May 2008 and September 2009 were registered in the Tsurumai Biologics Communication Registry. Data were collected at initiation of treatment (baseline) and over 52 weeks for Disease Activity Score 28-ESR (DAS28-ESR), Boolean core measurements, serum CRP levels and matrix metalloproteinase-3 levels. To compare clinical results, patients were divided into three groups based on treatment time required to achieve normal CRP levels.Results Multivariate analysis using the Cox proportional-hazards regression model found that higher CRP levels at baseline was a significant and independent factor in predicting normal CRP levels over 52 weeks (hazard ratio 0.86 per 1 mg/dL). In contrast, disease duration, concomitant methotrexate use and previous tumour necrosis factor inhibitor failure were not significant factors. Patients with normal CRP levels at 12 weeks of TCZ treatment achieved better clinical outcomes, including remission based on DAS28-ESR criteria, compared to patients with elevated CRP levels at 12 weeks.Conclusions Adequate suppression of pathological IL-6 signalling during TCZ treatment improves clinical outcomes and can be monitored with serum CRP levels, a readily available biomarker in clinical practice.

AB1160 Golimumab in 25 young adults affected by juvenile idiopathic arthritis (JIA) non responders to other biological agents: Preliminary data

BackgroundBiological agents licensed in JIA have demonstrated a favourable benefit-to-risk profile. Nevertheless, intolerance, loss and lack of efficacy or adverse events have led to try other therapeutic options.ObjectivesTo evaluate efficacy...

FRI0243 Act-life study: patterns of tocilizumab use, and dosing among patients with rheumatoid arthritis in the clinical practice.

BackgroundCurrently, there is not substantial evidence about tocilizumab (TCZ) use for the treatment of rheumatoid arthritis (RA) outside of clinical trials.ObjectivesTo describe usage patterns and dosage of TCZ, as well...

AB0540 Patterns of tocilizumab use, and dosing among patients with rheumatoid arthritis in the clinical practice. Preliminary analyses of act-life study

BackgroundCurrently, the available evidence about tocilizumab (TCZ) use for the treatment of rheumatoid arthritis (RA) in daily clinical practice is scarce.ObjectivesTo describe usage patterns of TCZ and reasons for dosage...