A framework for longitudinal latent factor modelling of treatment response in clinical trials with applications to Psoriatic Arthritis and Rheumatoid Arthritis.

OBJECTIVE: Clinical trials involve the collection of a wealth of data, comprising multiple diverse measurements performed at baseline and follow-up visits over the course of a trial. The most common primary analysis is restricted to a single, potentially composite endpoint at one time point. While such an analytical focus promotes simple and replicable conclusions, it does not necessarily fully capture the multi-faceted effects of a drug in a complex disease setting. Therefore, to complement existing approaches, we set out here to design a longitudinal multivariate analytical framework that accepts as input an entire clinical trial database, comprising all measurements, patients, and time points across multiple trials. METHODS: Our framework composes probabilistic principal component analysis with a longitudinal linear mixed effects model, thereby enabling clinical interpretation of multivariate results, while handling data missing at random, and incorporating covariates and covariance structure in a computationally efficient and principled way. RESULTS: We illustrate our approach by applying it to four phase III clinical trials of secukinumab in Psoriatic Arthritis (PsA) and Rheumatoid Arthritis (RA). We identify three clinically plausible latent factors that collectively explain 74.5% of empirical variation in the longitudinal patient database. We estimate longitudinal trajectories of these factors, thereby enabling joint characterisation of disease progression and drug effect. We perform benchmarking experiments demonstrating our method's competitive performance at estimating average treatment effects compared to existing statistical and machine learning methods, and showing that our modular approach leads to relatively computationally efficient model fitting. CONCLUSION: Our multivariate longitudinal framework has the potential to illuminate the properties of existing composite endpoint methods, and to enable the development of novel clinical endpoints that provide enhanced and complementary perspectives on treatment response.

Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease.

BACKGROUND: Acute graft-versus-host disease (GVHD) remains a major limitation of allogeneic stem-cell transplantation; not all patients have a response to standard glucocorticoid treatment. In a phase 2 trial, ruxolitinib, a selective Janus kinase (JAK1 and JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory acute GVHD. METHODS: We conducted a multicenter, randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator's choice of therapy from a list of nine commonly used options (control) in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28. The key secondary end point was durable overall response at day 56. RESULTS: A total of 309 patients underwent randomization; 154 patients were assigned to the ruxolitinib group and 155 to the control group. Overall response at day 28 was higher in the ruxolitinib group than in the control group (62% [96 patients] vs. 39% [61]; odds ratio, 2.64; 95% confidence interval [CI], 1.65 to 4.22; P<0.001). Durable overall response at day 56 was higher in the ruxolitinib group than in the control group (40% [61 patients] vs. 22% [34]; odds ratio, 2.38; 95% CI, 1.43 to 3.94; P<0.001). The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group and 39% in the control group. The median failure-free survival was considerably longer with ruxolitinib than with control (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non-relapse-related death, or addition of new systemic therapy for acute GVHD, 0.46; 95% CI, 0.35 to 0.60). The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (hazard ratio for death, 0.83; 95% CI, 0.60 to 1.15). The most common adverse events up to day 28 were thrombocytopenia (in 50 of 152 patients [33%] in the ruxolitinib group and 27 of 150 [18%] in the control group), anemia (in 46 [30%] and 42 [28%], respectively), and cytomegalovirus infection (in 39 [26%] and 31 [21%]). CONCLUSIONS: Ruxolitinib therapy led to significant improvements in efficacy outcomes, with a higher incidence of thrombocytopenia, the most frequent toxic effect, than that observed with control therapy. (Funded by Novartis; REACH2 ClinicalTrials.gov number, NCT02913261.).

Pain and Fatigue in Patients With Ankylosing Spondylitis Treated With Tumor Necrosis Factor Inhibitors: Multinational Real-World Findings.

BACKGROUND/OBJECTIVE: Patients with ankylosing spondylitis (AS) experience symptoms and comorbidities that impact their health-related quality of life (HRQoL) and ability to work. This real-world, global survey was conducted among AS patients receiving tumor necrosis factor inhibitors (TNFis) to evaluate both the frequency and severity of persistent symptoms, and the impact of pain and fatigue on HRQoL, employment status, and work activity. METHODS: Patients with AS and their treating physicians from 13 countries across 5 continents completed questionnaires capturing demographics, patient symptoms, current disease status, HRQoL, current therapy, employment status, and Work Productivity and Activity Impairment. RESULTS: Seven hundred five patients who had been receiving a TNFi for 3 months or more and completed both Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) pain and fatigue domains were included in the analysis; of these, 37.6% reported high BASDAI pain scores and 41.3% high BASDAI fatigue scores. Medical Outcomes Study-Short Form, 36-item version 2 domain, 5-dimensional EuroQoL Questionnaire, and 5-dimensional EuroQoL visual analog scale scores were significantly lower (p < 0.0001), and Work Productivity and Activity Impairment scores significantly higher (p < 0.0001), in patients with high levels of pain or fatigue than low levels. CONCLUSIONS: Globally, levels of pain and fatigue remained high in AS patients receiving TNFi treatment, which were significantly associated with reduced HRQoL and work productivity. Such persistent symptoms in usual care suggest a substantial unmet need in AS pharmacologic and nonpharmacologic therapeutic pathways.

Secukinumab provides rapid and persistent relief in pain and fatigue symptoms in patients with ankylosing spondylitis irrespective of baseline C-reactive protein levels or prior tumour necrosis factor inhibitor therapy: 2-year data from the MEASURE 2 study.

OBJECTIVES: To evaluate improvement in pain and fatigue in ankylosing spondylitis (AS) patients treated with secukinumab over 2 years (MEASURE 2 study). METHODS: Patients with active AS were randomised to receive secukinumab 150 mg, 75 mg, or placebo weekly until Week 4, and every 4 weeks thereafter. This post hoc analysis included assessment of spinal and nocturnal back pain, FACIT-Fatigue, and association between pain and either FACIT-Fatigue or ASQoL item 5 (sleep quality) for the approved secukinumab 150 mg dose in the overall population, and stratified by baseline high-sensitivity C-reactive protein (hsCRP) levels (normal [<5 mg/L] or elevated [≥5 mg/L]) or prior TNF inhibitor therapy status (TNFi-naïve or inadequate response [TNFi-IR]). RESULTS: Secukinumab-treated patients reported rapid improvement in pain and fatigue scores in overall population by Weeks 1 and 4, respectively; this trend of improvement was also observed irrespective of baseline hsCRP levels or prior TNFi therapy. Mean change at Week 16 in spinal/nocturnal pain (secukinumab vs. placebo) for the subgroups were -34.6/-30.2 vs. -16.6/-10.0, p<0.05/0.01 (normal hsCRP); -26.7/-31.6 vs. -7.8/-9.3, p<0.001/0.0001 (elevated hsCRP); -33.2/-35.4 vs. -13.2/-14.9, both p<0.0001 (TNFi-naïve); and -22.5/-22.8 vs. -9.4/-4.0, p=0.06/p<0.01 (TNFi-IR). FACIT-Fatigue was 7.1 vs. 3.3, p=0.15 (normal hsCRP); 8.7 vs. 3.6, p<0.05 (elevated hsCRP); 10.0 vs. 5.2, p<0.05 (TNFi-naïve); and 5.7 vs. 0.5, p=0.06 (TNFi-IR). These improvements were sustained or further improved through Week 104. CONCLUSIONS: Secukinumab provides rapid and sustained relief of pain and fatigue over 2 years in patients with AS regardless of baseline hsCRP levels and prior TNFi therapy.

Rapid smoking may not be aversive in schizophrenia.

INTRODUCTION: Aversive smoking has been investigated as a smoking cessation technique that involves rapid smoking in a clinic or laboratory and typically involves (a) puffing every 6-10 s or (b) smoking 3 or more cigarettes sequentially in 8-20 min. Rapid smoking usually results in dizziness, sore throat, nausea, and other unpleasant feelings. METHODS: To explore rapid smoking, 161 smokers (75 with schizophrenia [SS]; 86 controls [CON]) were assessed in a single day (24 ± 2 hr), ad libitum smoking topography session using the Clinical Research Support System micro portable topography device. RESULTS: SS smoked significantly more cigarettes in the 24-hr period versus CON and the time between puffs, or interpuff interval (IPI) was shorter in SS versus CON by an average of 6.5 s (p < .001). The median IPI was also significantly shorter in SS versus CON (9.3 vs.15.7 s; p < .001). SS were twice as likely to have IPIs ≤ 6 s than CON (OR = 2.32, 95% CI = 1.68, 3.20; p < .001). SS were also more likely to smoke 3 or more cigarettes in any 20 min during a 24-hr topography session (OR = 2.32, 95% CI = 1.03, 2.44; p < .001). Rapid smoking was associated with baseline characteristics of smoking more cigarettes per day, higher Fagerström score, and higher carbon monoxide level but not with serum cotinine values or trans-3'-hydroxycotinine/cotinine ratios. CONCLUSIONS: Using either definition, SS exhibit patterns of rapid smoking that they seemingly do not experience as aversive, since it reflects their naturalistic pattern of smoking, outside of the laboratory.

Caffeine levels and dietary intake in smokers with schizophrenia and bipolar disorder.

Caffeine is one of the most widely used psychoactive drugs in the United States. High rates of caffeine use have been observed in adult smokers as well as those with serious mental illness. The current secondary analysis aimed to extend previous findings demonstrating high caffeine intake in schizophrenia by examining dietary intake of caffeine and serum caffeine levels in outpatient smokers with schizophrenia (SCZ), bipolar disorder (BP) and control smokers with no psychiatric diagnoses (CON). Two hundred forty-eight adult smokers (SCZ=80; BP=80; CON=88) were included in the current study. Adult smokers with schizophrenia, bipolar disorder, and no psychiatric diagnoses were 40.85 (SD = 11.90) years old on average and all participants were current smokers (∼20 cigarettes per day). Twenty-four hour self-reported caffeine intake (in mg) was highest among individuals with bipolar disorder (median=195.3), followed by adults with schizophrenia (median=155.0) and controls (median=131.7). Participants with bipolar disorder also had the highest serum caffeine levels (in ng/ml; median=1725), followed by those with schizophrenia (median=1194) and controls (median=613.2).  These results provide additional evidence of high caffeine intake among adults with schizophrenia and extend findings by identifying even higher rates of caffeine use in those with bipolar disorder. The current study suggests that caffeine intake is higher among subgroups of patients with serious mental illness.

Nicotine intake and smoking topography in smokers with bipolar disorder.

OBJECTIVES: Cigarette smoking behavior in bipolar disorder (BPD), including the effects of mood-stabilizing medications, has not been well characterized. METHODS: We compared serum nicotine, nicotine metabolite levels, and smoking topography in 75 smokers with BPD to 86 control smokers (CON). For some comparisons, an additional control group of 75 smokers with schizophrenia (SCZ) were included. RESULTS: There were no differences between the BPD and CON groups in baseline smoking characteristics or serum nicotine or cotinine levels. Fifty-one smokers with BPD (68.9%) were taking one of the following mood stabilizers: valproic acid, lamotrigine, carbamazepine, oxcarbazepine, lithium, or topiramate. The 3-hydroxycotinine-to-cotinine ratio, a marker of cytochrome P450 2A6 (CYP2A6) metabolic activity, was significantly higher in BPD versus CON and versus SCZ (0.68 versus 0.49 versus 0.54; p =0.002). The difference between groups, however, was no longer significant when the analysis was repeated with those taking hepatic enzyme-inducing drugs (carbamazepine, oxcarbazepine, and topiramate) included as a covariate. The time between puffs, or interpuff interval (IPI), was shorter in BPD versus CON by an average of 3.0sec (p<0.05), although this was no longer significant when we removed smokers from the analysis of those taking hepatic enzyme inducers. CONCLUSIONS: Smokers with BPD are not different from CON on most measures of nicotine intake and smoking topography. We found an increased rate of nicotine metabolism in smokers taking mood stabilizers that are hepatic enzyme inducers, including carbamazepine, oxcarbazepine, and topiramate. Smokers with rapid nicotine metabolism might be expected to smoke more intensely to compensate for the more rapid disappearance of nicotine from the blood and brain, and may have more difficulty in quitting smoking, although this requires further study.

Isolated left side superior vena cava in a dialysis patient: Right direction, wrong turn!

Tunneled catheter insertion is a routine procedure undertaken by nephrologists world over. However, the presence of a venous anomaly can always test one's skills and can give them anxious moments. Persistent left superior vena cava (SVC) is the most common venous anomaly. We share our experience of successfully placing a hemodialysis central venous catheter in a very rare congenital anomaly wherein patient had persistent left SVC with agenesis of the right SVC.

Evaluation of the CHOICES program of peer-to-peer tobacco education and advocacy.

CHOICES is a consumer driven program for addressing tobacco in people with mental illness that employs mental health peer counselors. Since 2005, CHOICES has conducted over 298 community visits reaching more than 10,000 smokers with mental illness (about 2500/year). A telephone based outcome study was conducted in 102 outpatient smokers who received a CHOICES peer-to-peer session. At 1-month follow up participants (N = 86; 84%) reported smoking an average of 13 cigarettes per day which was significantly reduced from a baseline of 19 (P < 0.001). Twenty-five individuals (29%) tried to quit smoking in the month after the peer session and another 47 (55%) reduced their smoking. Feedback from smokers about the program was positive. Most (N = 59, 71%) said it was a lot easier to talk with a consumer about smoking compared to their psychiatrist or staff. Peer-to-peer communication about tobacco use can be effective to increase awareness and change smoking behaviors.

A comprehensive model for mental health tobacco recovery in new jersey.

Despite the high prevalence of tobacco use, disproportionate tobacco consumption, and excess morbidity and mortality, smokers with mental illness have reduced access to tobacco dependence treatment across the health care spectrum. We have developed a comprehensive model for Mental Health Tobacco Recovery in New Jersey (MHTR-NJ) that has the overarching goal of improving tobacco cessation for smokers with serious mental illness. Important steps involve engaging patients, professionals and the community to increase understanding that addressing tobacco use is important. In addition to increasing demand for tobacco treatment services, we must educate mental health professionals in evidence-based treatments so that patients can seek help in their usual behavioral health care setting. Peer services that offer hope and support to smokers are essential. Each of the policy or cessation initiatives described address the two core goals of this model: to increase demand for tobacco cessation services for mentally ill smokers and to help more smokers with mental illness to quit. Each has been pilot tested for feasibility and/or effectiveness and revised with feedback from stakeholders. In this way this implementation model has brought together academics, clinicians, administrators and mental health consumers to develop tobacco programming and policy that has been tested in a real world environment and serves as a model for other states.

Pica in a Patient With Decompensated Schizophrenia.

Although pica is commonly associated with nutritional deficiencies, it is also observed in psychiatric disorders such as obsessive-compulsive disorder and less commonly in schizophrenia. We describe a case of pica in a 34-year-old male with decompensated schizophrenia. Emergency medical services brought the patient from a state facility as he was scavenging and eating foreign objects. Upon initial evaluation, no notable nutritional deficiencies were noted. After surgical removal of foreign objects, he was started on antipsychotics. His pica was determined to be due to his active psychosis involving delusions, disorganized thought processes, and loosening of associations. His psychosis improved on paliperidone intramuscular injection and oral olanzapine, which coincided with reduction and resolution of pica. Our case highlights the need to understand further the exact psychopathology of pica that may not be limited to nutritional deficiencies.

Cannabis-Induced Malignant Catatonia: A Medical Emergency and Review of Prior Case Series.

Few case reports of catatonia associated with cannabis use are reported. Here, we describe a case of a 35-year-old African American male who developed malignant catatonia following heavy cannabis use. The patient was brought to the emergency department (ED) for altered mental status, hypertension, and erratic behavior. Before his ED presentation, he was smoking cannabis in heavy amounts, confirmed by positive urine toxicology in ED. Initial lab results showed leukocytosis, elevated creatine phosphokinase (CPK) levels. Head CT scans without contrast, including cerebrospinal fluid (CSF) analysis, were nonsignificant. In ED, the patient was agitated, combative, mute, and rigid. He was sedated using 2 mg of intramuscular (IM) midazolam. Psychiatric consultation services suspected catatonia, and the patient scored 12 points on Bush-Francis Catatonia Rating Scale (BFCRS). Although the patient's symptoms responded to 2 mg of IM lorazepam, the patient later relapsed, became tachycardic with blood pressure fluctuations, and his repeat BFCRS score was 18. At this point, the patient was diagnosed as having malignant catatonia, and his lorazepam dosage was increased up to 6 mg IM per day. After a few days of waxing and waning of his symptoms, he finally started to show constant improvement and gradually reduced his symptoms. Our case highlights the first-ever reported case of malignant catatonia associated with cannabis use.

Higher nicotine levels in schizophrenia compared with controls after smoking a single cigarette.

INTRODUCTION: The increase in blood nicotine after smoking a single cigarette is nicotine boost. We hypothesized that smokers with schizophrenia (SCZ) have a greater nicotine boost than controls without this disorder. METHODS: Twenty-one subjects (11 SCZ and 10 controls, CON) had repeated venous blood sampling before, during, and after smoking a single cigarette after 12-hr abstinence to measure nicotine concentrations. Blood samples were drawn at baseline (before smoking) and 1, 2, 4, 6, 8, 10, 20, 30, 60, 90, and 120 min after the first puff. Groups were similar in baseline characteristics, including gender and level of dependence, and all smoked 20-30 cigarettes/day. Area under the serum nicotine concentration-time curve (AUC(20)) was calculated for time up to 20 min after the start of smoking. RESULTS: The mean difference in AUC(20) was significantly greater for SCZ versus CON (135.4 ng-min/ml; 95% CI = 0.45-283.80). The shape of the nicotine concentration-time curve for SCZ was significantly different compared with controls (p < .01). Nicotine boost in the first 4 min of smoking was higher in SCZ versus CON (25.2 vs. 11.1 ng/ml, p < .01) with no difference in the total time spent smoking. DISCUSSION: This technique improves on methods, which draw only two blood specimens to assess nicotine intake. Understanding how nicotine boost differs in SCZ from CON may explain high levels of addiction and low success in cessation in smokers with SCZ.

Correction to: Retransplantation after post transplant lymphoproliferative disorder: overcoming the obstacles!

In the original publication of the article, while submitting the case report.

Relationship of pain and fatigue with health-related quality of life and work in patients with psoriatic arthritis on TNFi: results of a multi-national real-world study.

BACKGROUND/OBJECTIVE: The incidence of pain and/or fatigue in people with psoriatic arthritis (PsA) is associated with reduced health-related quality of life (HRQoL) and the ability to work, despite modern advanced therapeutic approaches. This real-world, international study examined these relationships in patients with PsA treated with tumour necrosis factor inhibitors (TNFi). METHODS: Data from 13 countries were analysed. Patients with PsA and their physicians completed questionnaires capturing demographics, current therapy, current disease status, HRQoL and work status via Medical Outcomes Study 36-Item Short-Form version 2 (SF-36v2), 3-level 5-dimension EuroQoL questionnaire, Health Assessment Questionnaire Disability Index, and Work Productivity and Activity Impairment (WPAI) questionnaire. RESULTS: 640 patients with PsA were included who had been receiving TNFi for ≥3 months and had completed SF-36v2 bodily pain and vitality domains. Of these, 33.1%, 29.2% and 37.7% of patients reported no, moderate and severe pain, respectively, and 31.9%, 22.5% and 45.6% of patients reported low, moderate and severe fatigue, respectively. Scores across HRQoL variables and WPAI were significantly different across pain and fatigue cohorts (all p<0.0001), with HRQoL and WPAI measures considerably worse in patients with moderate to severe pain or fatigue than those with low pain or fatigue. CONCLUSIONS: Despite treatment with biologic agents such as TNFi, data from this global study demonstrated that substantial pain and/or fatigue persist in patients with PsA and that these are significantly associated with reduced HRQoL, physical function and work productivity. These findings suggest that there is an unmet need for additional PsA therapies.

Retransplantation after post transplant lymphoproliferative disorder: overcoming the obstacles!

Post transplant lymphoproliferative disorder (PTLD) is a rare complication after kidney transplantation. Graft dysfunction is often encountered during the course of the treatment of PTLD, at times leading to need for retransplantation. We describe here the case of a young boy who underwent retransplantation after treatment of early Epstein Barr virus (EBV) related post transplant lymphoproliferative disorder. Our case highlights the various factors needing deliberation before retransplantation including time from remission of PTLD, EBV serostatus and choice of induction and maintenance immunosuppression agents.

Rare Occurrence of PLA2R-Positive Membranous Nephropathy in a Patient with Sjogren's Syndrome and CIDP.

Membranous nephropathy is known to be associated with number of autoimmune diseases. Occurrence of PLA2R positive membranous nephropathy with sjogren's syndrome and chronic inflammatory demyelinating neuropathy (CIDP) is quite rare. Role of PLA2R antigen in autoimmune diseases like sjogren's syndrome and CIDP is largely unknown. Choice and initiation of immunosuppression if required may also be governed by the presence of other autoimmune diseases along with PLA2R positive membranous nephropathy.

Comparison of remission and low disease activity states with DAPSA, MDA and VLDA in a clinical trial setting in psoriatic arthritis patients: 2-year results from the FUTURE 2 study.

OBJECTIVES: Remission (REM) or low disease activity (LDA) states were compared in a clinical trial setting of the FUTURE 2 study (NCT01752634) using Disease Activity Index for Psoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) composite indices in secukinumab treated PsA patients. METHODS: The proportion of patients reaching DAPSA-REM (cut-off ≤4) or REM+LDA (≤14), and very low disease activity (VLDA; achieving 7/7 criteria) or MDA (≥5/7), were compared in the overall population, by prior use of anti-TNF therapy, and by time since diagnosis using as observed data. The proportion of patients who met individual core component and other variables of interest were also computed to assess residual disease activity in DAPSA-REM/REM+LDA states and VLDA/MDA responses. The relationship between DAPSA/MDA and patient reported outcomes (PROs), including health-related quality of life, physical function, and fatigue were assessed using mixed model for repeated measures. RESULTS: More patients could achieve DAPSA-REM or DAPSA-REM+LDA status than VLDA or MDA responses, respectively, at all the time points in the overall population, irrespective of anti‒TNF status and time since diagnosis. Higher proportion of patients reaching DAPSA-REM or VLDA achieved more thresholds of core components (joints, pain, patient and physician global assessments, and function) than DAPSA-REM+LDA or MDA over Week 104. There were differences with numerically higher proportion of patients achieving patient global assessment ≤10 mm and ≤20 mm, and physician global assessment ≤10 mm with MDA than with DAPSA-REM+LDA, and patient pain VAS ≤15 mm, PASI ≤1, HAQ ≤0.5 with VLDA or MDA than with DAPSA-REM or DAPSA-REM+LDA, respectively, through 104 weeks. Improvements in PROs were significantly better for patients in DAPSA-REM+LDA versus DAPSA-moderate+high disease activity status, and for MDA responders versus non-responders. CONCLUSION: These analysis add to the evidence that both DAPSA and MDA composite index measures can be used for evaluation of the status and treatment response utilizing a treat to target approach in PsA patients in a clinical trial setting and improve patient health related outcomes. FUNDING: The study and analysis was funded by Novartis Pharma AG, Basel, Switzerland.

Comparative effectiveness of secukinumab and etanercept in biologic-naïve patients with psoriatic arthritis assessed by matching-adjusted indirect comparison.

OBJECTIVE: Matching-adjusted indirect comparison (MAIC) can be used to assess the comparative effectiveness of two treatments indirectly using data from randomized placebo-controlled trials. This MAIC assessed the comparative effectiveness of secukinumab (an anti-interleukin-17A) and etanercept (a tumor necrosis factor inhibitor) in a target population of biologic-naïve patients with psoriatic arthritis (PsA). METHODS: Individual patient data pooled from FUTURE 2 (NCT01752634), FUTURE 3 (NCT01989468), and FUTURE 5 (NCT02404350) (secukinumab: 150 mg, n=458 and 300 mg, n=461) were matched to data from the population in the NCT00317499 trial (etanercept 25 mg, n=101) using MAIC methodology, by adjusting for clinical and demographic baseline characteristics. Recalculated outcomes from FUTURE 2, 3, and 5 (150 mg, effective sample size (ESS) post-matching=104; 300 mg, ESS=75; and placebo, ESS=159) were compared with the NCT00317499 trial. Pairwise comparisons using odds ratios (ORs) were performed for the American College of Rheumatology (ACR) 20, 50, and 70 response criteria at week 12 (placebo-adjusted) and week 24 (non-placebo-adjusted). RESULTS: At week 12, there were no significant differences in ACR responses between secukinumab and etanercept. There was no significant difference between secukinumab 150 mg and etanercept at week 24 with respect to ACR 20 and 50 response rates; however, ACR 70 response rates were higher for secukinumab 150 mg (OR (95% confidence interval (CI)): 4.48 (2.01-9.99), p<0.001). ACR 20, 50, and 70 response rates were higher with secukinumab 300 mg than with etanercept at this time point (OR (95% CI): ACR 20, 3.28 (1.69-6.38), p<0.001; ACR 50, 1.90 (1.04-3.50), p=0.038; and ACR 70, 3.56 (1.51-8.40), p=0.004). CONCLUSION: In this MAIC, secukinumab was associated with higher ACR 20 and 50 (secukinumab 300 mg) and 70 (secukinumab 150 mg and 300 mg) response rates at week 24 than etanercept in biologic-naïve patients with active PsA, whereas no significant difference was observed in the short-term at week 12.

Matching-adjusted indirect comparison: secukinumab versus infliximab in biologic-naive patients with psoriatic arthritis.

Aim: To compare secukinumab with infliximab in biologic-naive patients with psoriatic arthritis using matching-adjusted indirect comparison. Patients & methods: Individual patient baseline data for secukinumab were matched to published aggregate data for infliximab by key baseline characteristics, with matching weights determined by logistic regression, and used to recalculate American College of Rheumatology (ACR) responses for secukinumab, for comparison with infliximab. Results: There were no differences in outcomes between secukinumab and infliximab at weeks 6/8 and 14/16. At weeks 24 and 54/52, ACR 20 responses were higher with secukinumab 150 mg than infliximab. At week 54/52, ACR 20/50 responses were higher for secukinumab 300 mg than infliximab. Conclusion: In the mid to long term, patients receiving secukinumab were more likely to achieve ACR 20/50 responses than those receiving infliximab.