Real-world evidence for secukinumab in UK patients with psoriatic arthritis or radiographic axial spondyloarthritis: interim 2-year analysis from SERENA.

Objectives: The aim was to evaluate retention rates for secukinumab in patients with active PsA or radiographic axial spondyloarthritis (r-axSpA) treated in routine UK clinical practice. Methods: SERENA (CAIN457A3403) is an ongoing, non-interventional, international study of patients with moderate-to-severe chronic plaque psoriasis, active PsA or active r-axSpA, who had received secukinumab for ≥16 weeks before enrolment. The primary objective of this interim analysis was to assess treatment retention rates in patients with PsA or r-axSpA who were enrolled and followed for ≥2 years at centres in the UK. The safety analysis set includes all patients who received at least one dose of secukinumab. The target population set includes all patients who fulfilled the patient selection criteria. Results: The safety set comprised 189 patients (PsA, n = 81; r-axSpA, n = 108), and the target population set comprised 183 patients (PsA, n = 78; r-axSpA, n = 105). In the safety set, 107 patients (45 of 81 with PsA and 62 of 108 with r-axSpA) had previously received a biologic agent. Retention rates were similar between patients with PsA and r-axSpA after 1 year (PsA 91.0%, 95% CI: 84.0, 98.0; r-axSpA 89.2%, 95% CI: 82.7, 95.7) and 2 years (PsA 77.6%, 95% CI: 67.6, 87.7; r-axSpA 76.2%, 95% CI: 67.4, 85.0) of observation. Overall, 17.5% of patients (33 of 189) experienced at least one treatment-related adverse event, and 12.7% of patients (24 of 189) discontinued secukinumab because of adverse events. Conclusion: This analysis of real-world data from the UK demonstrates high retention rates for secukinumab over 2 years in patients with PsA or r-axSpA, with a favourable safety profile.

Retention of subcutaneous abatacept for the treatment of rheumatoid arthritis: real-world results from the ASCORE study: an international 2-year observational study.

OBJECTIVES: To evaluate retention, efficacy, and safety of subcutaneous (SC) abatacept over 2 years in patients with moderate-to-severe RA in the Abatacept SubCutaneOus in Routine clinical practicE (ASCORE) study. METHODS: Patients with RA who initiated SC abatacept 125 mg once weekly were enrolled in the international, observational, prospective multicentre ASCORE study into biologic-naïve or ≥ 1 prior biologic failure cohorts. PRIMARY ENDPOINT: abatacept retention rate at 2 years. Secondary endpoints: proportion of patients with good/moderate EULAR response rates based on DAS28 (ESR), low disease activity and/or remission according to DAS28 (ESR; ≤ 3.2/ < 2.6), SDAI (≤ 11/ ≤ 3.3), CDAI (≤ 10/ ≤ 2.8), and Boolean criteria. Retention rate by baseline serostatus was evaluated post hoc. RESULTS: Overall, 47% of patients remained on abatacept for 2 years, irrespective of treatment line. Higher abatacept retention rates were associated with lower prior biologic exposure. Generally, clinical outcomes showed that the proportion of patients with low disease activity/remission was higher in biologic-naïve patients (vs biologic-failure) and similar in those with 1 and ≥ 2 prior biologic failures. In patients on treatment at 2 years, good/moderate EULAR response rates of ~ 80% were consistently noted irrespective of prior biologic exposure. Across treatment lines, retention was greater in patients with seropositive (vs seronegative) RA. Patients with rheumatoid factor/anti-citrullinated protein antibody single-positive RA who were bio-naïve had higher retention than patients who were bio-experienced. CONCLUSIONS: In the ASCORE study, SC abatacept retention was 47% at 2 years with good clinical outcomes and was well-tolerated in the real-world setting. Abatacept retention and clinical response rates were higher in patients who received abatacept as an earlier- versus later-line biologic drug treatment and in those with seropositive RA. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02090556.

Efficacy and safety of secukinumab in patients with spondyloarthritis and enthesitis at the Achilles tendon: results from a phase 3b trial.

OBJECTIVE: ACHILLES aimed to demonstrate efficacy of secukinumab on Achilles' tendon enthesitis in spondyloarthritis (SpA) patients. METHODS: Patients ≥18 years (n = 204) with active PsA or axial SpA and heel enthesitis were randomized 1:1 to secukinumab 150/300 mg or placebo up to week 24, and thereafter placebo patients were switched to secukinumab. RESULTS: At week 24, a higher, yet statistically non-significant (P = 0.136), proportion of patients in secukinumab vs placebo reported resolution of Achilles tendon enthesitis in affected foot (42.2% vs 31.4%; odds ratio [OR] = 1.63; 95% CI: 0.87, 3.08). Proportion of patients reporting resolution of enthesitis based on Leeds Enthesitis Index was higher with secukinumab vs placebo (33.3% vs 23.5%; OR = 1.65; 95% CI: 0.85, 3.25) at week 24. Mean change from baseline in heel pain at week 24 was higher in secukinumab patients vs placebo (-2.8 [3.0] vs -1.9 [2.7]). Greater improvements with secukinumab were observed in heel enthesopathy activity and global assessment of disease activity. Imaging evaluation by local reading confirmed heel enthesitis on MRI at screening for all patients. Based on central reading, 56% presented with bone marrow oedema and/or tendinitis; according to Heel Enthesitis MRI Scoring System (HEMRIS) post hoc analysis, 76% had signs of entheseal inflammation while 86% had entheseal inflammation and/or structural changes. CONCLUSION: A substantial proportion of patients showed no signs of inflammation on the centrally read MRIs despite a clinical diagnosis of heel enthesitis, thus highlighting that the discrepancy between the clinical and imaging assessments of enthesitis requires further investigation. Although ACHILLES did not meet the primary end point, the study reported clinically meaningful improvements in patient-related outcomes. TRIAL REGISTRATION: clinicaltrials.gov, NCT02771210.

Response to SARS-CoV-2 vaccination in immune mediated inflammatory diseases: Systematic review and meta-analysis.

OBJECTIVES: The treatment for COVID-19 often utilizes immune-modulating drugs. These drugs are also used in immune mediated inflammatory diseases (IMIDs). We performed a systematic review about seroconversion after SARS-CoV-2 vaccination in patients with IMIDs and impact of various drugs on seroconversion rates. METHODS: Electronic databases were searched to identify relevant studies reporting seroconversion rates following SARS-CoV-2 vaccination in IMIDs. We calculated the pooled seroconversion rates after a single or two doses of vaccination, pooled seroconversion rates in patients with specific IMIDs, and rates in patients on various drugs/drug classes. RESULTS: Twenty-five studies were included in the systematic review. The pooled seroconversion rates after two doses of mRNA vaccination were higher (83.1, 95%CI: 74.9-89.0, I2 = 90%) as compared to a single dose (69.3, 52.4-82.3, I2 = 95%). The odds of seroconversion were lower in IMIDs as compared to healthy controls (0.05, 0.02-0.13, I2 = 21%). The seroconversion rates in patients with inflammatory bowel disease (95.2, 95%CI: 92.6-96.9, I2 = 0%), spondyloarthropathy (95.6, 95% CI: 83.4-98.9, I2 = 35%), and systemic lupus erythematosus (90.7, 95%CI: 85.4-94.2, I2 = 0%) were higher as compared to rheumatoid arthritis (79.5, 95% CI: 65.1-88.9, I2 = 85%), and vasculitis (70.5, 95% CI: 52.9-83.5, I2 = 51%). The seroconversion rates following double dose of mRNA were excellent (>90%) in those on anti-tumour necrosis factor (TNF), anti-integrin (vedolizumab), anti-IL 17 (secukinumab), anti-IL6 (Tocilizumab) and anti-IL12/23 (Ustekinumab) therapies but attenuated (<70%) in patients on anti-CD20 (Rituximab) or anti-cytotoxic T lymphocyte associated antigen (CTLA-4) therapies (Abatacept). The seroconversion rates were good (70-90%) with steroids, hydroxychloroquine, JAK inhibitors, mycophenolate mofetil and leflunomide. Combination of anti-TNF with immunomodulators (azathioprine, 6-meracptopurine, methotrexate) resulted in an attenuated vaccine response as compared to anti-TNF monotherapy. CONCLUSION: Seroconversion rates after SARS-CoV-2 vaccination are lower in patients with IMIDs. Certain therapies (anti-TNF, anti-integrin, anti-IL 17, anti-IL6, anti-12/23) do not impact seroconversion rates while others (anti-CD20, anti-CTLA-4) result in poorer responses.

Outcomes in rheumatoid arthritis patients treated with abatacept: a UK multi-centre observational study.

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that causes chronic synovitis, resulting in progressive joint destruction and functional disability and affects approximately 400,000 people in the UK. This real-world study aimed to describe the characteristics, treatment patterns and clinical outcomes of patients who received abatacept in UK clinical practice. METHODS: This was a multi-centre, retrospective, observational study of patients with RA treated with abatacept at four UK centres between 01 January 2013 and 31 December 2017. Data were collected from medical records of each patient from the index date (date of first bDMARD initiation) until the most recent visit, death or end of study (31 December 2017). RESULTS: In total, 213 patients were included in the study. Patients received up to eight lines of therapy (LOTs). Treatment with abatacept, or any other bDMARD, was associated with reductions in DAS28-ESR and DAS28-CRP scores at 6 and 12 months. The distribution of EULAR responses (good/moderate/no response) tended to be more favourable for patients when receiving abatacept than when receiving other bDMARDs (22.8%/41.3%/35.9% versus 16.6%/41.4%/42.1% at 6 months, and 27.9%/36.1%/36.1% versus 21.2%/34.5%/44.2% at 12 months). Patients receiving abatacept at LOT1 (n = 68) spent significantly longer on treatment compared with patients receiving other bDMARDs (53.4 vs. 17.4 months; p< 0.01); a similar trend was observed for LOT2. Among patients who discontinued after 6 months, a greater proportion experienced infection requiring antibiotics when receiving other bDMARDs compared to those receiving abatacept. CONCLUSIONS: RA patients who received bDMARDs, including abatacept, experienced reduced disease activity. When receiving abatacept as first or second line of therapy, patients persisted with treatment significantly longer than those receiving other bDMARDs.

Efficacy and safety of subcutaneous tocilizumab in rheumatoid arthritis over 1 year: a UK real-world, open-label study.

OBJECTIVE: The ACT-MOVE study assessed the real-world efficacy and safety of s.c. tocilizumab (TCZ-SC), provided as monotherapy or in combination with conventional synthetic DMARDs (csDMARDs) over 1 year, in patients with RA and an inadequate response to csDMARD therapy and/or first TNF inhibitor. METHODS: In this UK multicentre, open-label phase IIIb study, patients received TCZ-SC 162 mg once weekly for 52 weeks as monotherapy or with csDMARDs. Efficacy and safety were evaluated at baseline, weeks 2 and 4 and every 4 weeks thereafter up to week 52. RESULTS: Of 161 patients who received at least one dose of TCZ-SC, 21 (13.0%) received TCZ-SC alone and 140 (87.0%) TCZ-SC with a csDMARD(s). From baseline to week 52, there was a mean decrease in DAS28-ESR score among all patients (-3.68), and within monotherapy (-3.75) and combination therapy (-3.67) groups. The proportion of patients who achieved DAS28 clinical remission (DAS28-ESR <2.6) at week 52 was 75.4% (95% CI 66.8, 82.8). At the same time point, ≥80% of patients who remained on TCZ-SC achieved DAS28 clinical remission or had low disease activity (DAS28-ESR ≥2.6 and ≤3.2). Overall, 6.2% of patients had at least one serious adverse event (10.2/100 patient-years), and there was one death; 11.2% of patients discontinued owing to adverse events. CONCLUSION: TCZ-SC was effective and tolerated in a real-world setting over 1 year. The efficacy of TCZ-SC was similar whether given as monotherapy or with csDMARDs; its safety profile was consistent with that previously established. TRIAL REGISTRATION: ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT02046603.

Long-term effectiveness of tumour necrosis factor-α inhibitor treatment for psoriatic arthritis in the UK: a multicentre retrospective study.

OBJECTIVE: Real-world evidence of the long-term effectiveness of TNF-α inhibitor (TNFi) therapy in patients with PsA is limited. This study was conducted to describe patterns of TNFi therapy and treatment responses in patients with PsA treated in UK clinical practice. METHODS: A multicentre, retrospective, observational cohort study of consenting patients treated with TNFi for PsA with ≥3 years follow-up from first TNFi initiation (observation period) was carried out in 11 UK National Health Service hospitals. Data were collected concerning baseline patient characteristics, PsA-related treatment pathways and TNFi treatment responses (PsA response criteria components: swollen/tender joint counts, physician and patient global assessments). RESULTS: The mean age of patients (n = 141) was 50.3 (s.d.: 12.1) years (50% male). During a median observation period of 4.5 (range: 3.4-5.5) years, patients received a median of one (range: one to five) TNFi. Twelve-week response rates for first TNFi (where available) were as follows: 80% (n = 64/80) for swollen joint counts, 79% (n = 63/79) for tender joint counts, 79% (n = 37/47) for physician global assessments, 69% (n = 41/59) for patient global assessments and 79% (n = 37/47) for PsA response criteria. At the end of the observation period, the proportions of patients remaining on first, second, third and fourth/fifth TNFi were 56, 15, 5 and 3%, respectively; 21% of patients permanently discontinued TNFi therapy. CONCLUSION: Long-term TNFi therapy is generally well tolerated and may be effective; however, after initial TNFi failure, there appears to be progressively less benefit and more adverse effects with successive TNFi switches. Strategies are needed for effective therapy for PsA beyond the first TNFi failure.