Secukinumab versus adalimumab for psoriatic arthritis: comparative effectiveness up to 48 weeks using a matching-adjusted indirect comparison

Secukinumab and adalimumab are approved for adults with active psoriatic arthritis (PsA). In the absence of direct randomized controlled trial (RCT) data, matching-adjusted indirect comparison can estimate the comparative effectiveness in anti-tumor necrosis factor (TNF)-naïve populations. Individual patient data from the FUTURE 2 RCT (secukinumab vs. placebo; N = 299) were adjusted to match baseline characteristics of the ADEPT RCT (adalimumab vs. placebo; N = 313). Logistic regression determined adjustment weights for age, body weight, sex, race, methotrexate use, psoriasis affecting ≥ 3% of body surface area, Psoriasis Area and Severity Index score, Health Assessment Questionnaire Disability Index score, presence of dactylitis and enthesitis, and previous anti-TNF therapy. Recalculated secukinumab outcomes were compared with adalimumab outcomes at weeks 12 (placebo-adjusted), 16, 24, and 48 (nonplacebo-adjusted). After matching, the effective sample size for FUTURE 2 was 101. Week 12 American College of Rheumatology (ACR) response rates were not significantly different between secukinumab and adalimumab. Week 16 ACR 20 and 50 response rates were higher for secukinumab 150 mg than for adalimumab (P = 0.017, P = 0.033), as was ACR 50 for secukinumab 300 mg (P = 0.030). Week 24 ACR 20 and 50 were higher for secukinumab 150 mg than for adalimumab (P = 0.001, P = 0.019), as was ACR 20 for secukinumab 300 mg (P = 0.048). Week 48 ACR 20 was higher for secukinumab 150 and 300 mg than for adalimumab (P = 0.002, P = 0.027), as was ACR 50 for secukinumab 300 mg (P = 0.032). In our analysis, patients with PsA receiving secukinumab were more likely to achieve higher ACR responses through 1 year (weeks 16-48) than those treated with adalimumab. Although informative, these observations rely on a subgroup of patients from FUTURE 2 and thus should be considered interim until the ongoing head-to-head RCT EXCEED can validate these findings. Novartis Pharma AG

Psoriasis Area and Severity Index response in moderate-severe psoriatic patients switched to adalimumab: results from the OPPSA study

Background: Few studies have compared the efficacy of switching to adalimumab in the real-life setting in plaque psoriasis patients. Objective: To evaluate the effect of adalimumab in psoriasis patients previously treated with other biologics. Methods: In this multicentre study, psoriasis patients (N = 262) treated with an anti-TNF-alpha agent, ustekinumab or naïve to biologics then switched to adalimumab were included. Disease severity was assessed by the Psoriasis Area and Severity Index (PASI) at baseline and after 3, 6, 12, 24 and 36 months. The association between clinical risk factors and achievement of PASI response was evaluated by logistic regression. Results: Adalimumab treatment resulted in a decrease in PASI (15.1 ± 6.2 at baseline vs. 2.7 ± 4.8 at 6 months, P < 0.0001), regardless of previous biologic treatment. Furthermore, adalimumab allowed 92.5%, 79% and 56% of patients to achieve PASI response (PASI 50, 75 and 90, respectively) and complete remission (PASI 100 response) in 48.4% of patients, by 6 months and maintained over 3 years, independent of prior biologic treatment. The absence of metabolic syndrome, dyslipidemia, hypertension and lower PASI and lower age at baseline was associated with achievement of PASI response at 3, 6 and 12 months, whereas at later time points (24 and 36 months), PASI 90 and PASI 100 response was associated with diagnosis of psoriasis/psoriatic arthritis. Conclusion: Adalimumab was effective at reducing PASI score over 3 years, irrespective of whether patients were biologic naïve or previously treated with a TNF-alpha or IL-12/23 inhibitor

Randomized controlled trial of adalimumab in patients with nonpsoriatic peripheral spondyloarthritis

Objective. To evaluate the efficacy and safety of adalimumab in patients with active nonpsoriatic peripheral spondyloarthritis (SpA). Methods. ABILITY-2 is an ongoing phase III, multicenter study of adalimumab treatment. Eligible patients age 18 years fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for peripheral SpA, did not have a prior diagnosis of psoriasis, psoriatic arthritis (PsA), or ankylosing spondylitis (AS), and had an inadequate response or intolerance to nonsteroidal antiinflammatory drugs (NSAIDs). Patients were randomized 1:1 to receive adalimumab 40 mg every other week or matching placebo for 12 weeks, followed by a 144-week open-label period. The primary end point was the proportion of patients achieving 40% improvement in disease activity according to the Peripheral SpA Response Criteria (PSpARC40) at week 12. This was defined as 40% improvement from baseline (20-mm absolute improvement on a visual analog scale) in patient's global assessments of disease activity and pain, and 40% improvement in at least one of the following features: swollen joint and tender joint counts, total enthesitis count, or dactylitis count. Adverse events were recorded throughout the study. Results. In total, 165 patients were randomized to a treatment group, of whom 81 were randomized to receive placebo and 84 to receive adalimumab. Baseline demographics and disease characteristics were generally similar between the 2 groups. At week 12, a greater proportion of patients receiving adalimumab achieved a PSpARC40 response compared to patients receiving placebo (39% versus 20%; P = 0.006). Overall, improvement in other outcomes was greater in the adalimumab group compared to the placebo group. The rates of adverse events were similar in both treatment groups. Conclusion. Treatment with adalimumab ameliorated the signs and symptoms of disease and improved physical function in patients with active nonpsoriatic peripheral SpA who exhibited an inadequate response or intolerance to NSAIDs, with a safety profile consistent with that observed in patients with AS, PsA, or other immune-mediated diseases

Treatment of ankylosing spondylitis and extra-articular manifestations in everyday rheumatology practice

The SpAs are a group of overlapping, chronic, inflammatory rheumatic diseases including AS, a chronic inflammatory disease primarily affecting the SI joints. In addition to inflammatory back pain, AS patients are also more likely to experience extra-articular manifestations belonging to the SpA concept which can affect the eyes, the gastrointestinal tract and the skin and other related inflammatory conditions. This review focuses on current progress in treatment options in SpA with special emphasis on extra-articular features. TNF inhibition has demonstrated effectiveness in the treatment of AS symptoms and all currently available anti-TNF agents appear to have similar efficacy. However, the efficacy of anti-TNF agents varies in the treatment of extra-articular manifestations and comorbidities. Analyses of trials of anti-TNF agents in patients with AS have revealed significant reductions in the incidence of flares of uveitis and IBD with infliximab and adalimumab (uveitis only) treatment but not with etanercept. All three anti-TNF agents (infliximab, adalimumab, etanercept) have demonstrated efficacy in psoriasis (not associated with AS). When evaluating as to which agent to use in the treatment of AS, an important consideration is the overall well-being of the patient. This should include any additional inflammatory burden that manifests in other parts of the body, which may currently be subclinical. Based on current evidence, among TNF inhibitors, the monoclonal antibodies (infliximab and adalimumab) are more appropriate than etanercept if extra-articular manifestations or comorbid conditions are present or suspected. To date, infliximab appears to be the best studied agent with a wide spectrum of proven efficacy

Viewpoint on handling anti-TNF failure in psoriasis

An association among the occurrence of antidrug antibodies (ADAs), diminished trough serum drug levels (TSDLs) and non-response or loss of response has been described for several tumor necrosis factor alpha (TNF) blocking agents in a variety of diseases, including psoriasis. In a series of ten psoriasis patients with primary or secondary failure, or adverse reactions during anti-TNF therapy, we measured ADAs and TSDLs in patient serum using radioimmunoassay and ELISA, respectively. By proposing a treatment algorithm derived from research in this field, we show that measuring ADAs and TSDLs in psoriasis patients provides a more structured approach to clinical decision making for psoriasis patients who fail anti-TNF therapy

Use of biological drugs in patients with psoriasis and psoriatic arthritis in italy: Results from the PSONG survey

This Italian multicenter retrospective study compared the drug survival and efficacy of differentanti-TNF agents in psoriasis (PsO) and psoriatic arthritis (PsA) patients. A database of PsO/PsApatients treated with adalimumab, etanercept, and infliximab from May 2013 to May 2014 wasanalyzed. PASI 75, 90, and 100 was calculated at each time point to evaluate efficacy. Drug sur-vival rate and probability of maintaining PASI response were evaluated. The impact of dependentvariables on probability of PASI 75 loss was evaluated by logistic regression. 1,235 patients wereincluded, 577 with PsO and 658 with PsA. Highest survival rates were observed with adalimumabfollowed by etanercept and infliximab in PsO and PsA patients. The probability of maintainingPASI response was significantly higher for adalimumab followed by infliximab. For PsO patients,the odds of losing PASI 75 was higher in etanercept-treated patients (OR: 8.1; 95% CI: 4.2–15.6,p<.001) or infliximab (OR: 6.6; 95% CI: 2.6–16.3,p<.001) vs. adalimumab. Likewise, for PsApatients the odds of losing PASI 75 was higher in etanercept-treated patients (OR: 2.3; 95% CI:1.4–3.8,p5.01) or infliximab (OR: 2.2; 95% CI: 1.1–4.1,p5.018) vs. adalimumab. Adalimumabcould be the best therapeutic option over other anti-TNF agents for the treatment of PsO and PsApatients

Efficacy of adalimumab as second-line therapy in a pediatric cohort of crohn’s disease patients who failed infliximab therapy: The Italian society of pediatric gastroenterology, hepatology, and nutrition experience

Background: Adalimumab (Ada) treatment is an available option for pediatric Crohn’s disease (CD) and the published experience as rescue therapy is limited. Objectives: We investigated Ada efficacy in a retrospective, pediatric CD cohort who had failed previous infliximab treatment, with a minimum follow-up of 6 months. Methods: In this multicenter study, data on demographics, clinical activity, growth, laboratory values (CRP) and adverse events were collected from CD patients during follow-up. Clinical remission (CR) and response were defined with Pediatric CD Activity Index (PCDAI) score ≤10 and a decrease in PCDAI score of ≥12.5 from baseline, respectively. Results: A total of 44 patients were consecutively recruited (mean age 14.8 years): 34 of 44 (77%) had active disease (mean PCDAI score 24.5) at the time of Ada administration, with a mean disease duration of 3.4 (range 0.3–11.2) years. At 6, 12, and 18 months, out of the total of the enrolled population, CR rates were 55%, 78%, and 52%, respectively, with a significant decrease in PCDAI scores (P&lt;0.01) and mean CRP values (mean CRP 5.7 and 2.4 mL/dL, respectively; P&lt;0.01) at the end of follow-up. Steroid-free remission rates, considered as the total number of patients in CR who were not using steroids at the end of this study, were 93%, 95%, and 96% in 44 patients at 6, 12, and 18 months, respectively. No significant differences in growth parameters were detected. In univariate analysis of variables related to Ada efficacy, we found that only a disease duration &gt;2 years was negatively correlated with final PCDAI score (P&lt;0.01). Two serious adverse events were recorded: 1 meningitis and 1 medulloblastoma. Conclusion: Our data confirm Ada efficacy in pediatric patients as second-line biological therapy after infliximab failure. Longer-term prospective data are warranted to define general effectiveness and safety in pediatric CD patients

Clinical Evaluation of Risankizumab-rzaa in the Treatment of Plaque Psoriasis.

Risankizumab-rzaa (Skyrizi®; AbbVie) is a humanized IgG monoclonal antibody directed against interleukin-23p19 (IL-23p19) indicated for the treatment of moderate-to-severe psoriasis in adults who are candidates for systemic therapy or phototherapy. Four pivotal Phase III trials: UltIMMa-1, UltIMMa-2, IMMhance, and IMMvent have demonstrated efficacy and safety in patients with moderate-to-severe plaque psoriasis. This review highlights important findings from these and other clinical trials that have evaluated risankizumab. In addition, we discuss the mechanism of action, pharmacokinetics/pharmacodynamics, dosing recommendations, drug interactions, other potential indications, and ongoing clinical trials

Treatment of psoriasis with biologic agents in Malta

Introduction: Biologic therapy has revolutionalised the treatment of moderate to severe psoriasis leading to improved clinical outcomes and quality of life scores. This study aims to determine current biologic use in psoriatic patients at our Dermatology department at Sir Paul Boffa hospital, Malta. Method: All patients who were administered biologic therapy for psoriasis in Malta until the end of 2014 were included. Data included demographic details, disease duration and severity, biologic use and duration, previously attempted treatments, side effects, early and late response to biologic using Psoriasis Area Severity Index (PASI) scores and Dermatology Life Quality index (DLQI) scores. Results: A total of 36 patients were started on a biologic between 2009 and 2014 for psoriasis (M:25, F:11) with a mean age of 46.9 years. These included etanercept (n=22), infliximab (n=8), adalimumab (n=4) and ustekinumab (n=2). Secondary failure was the main reason why biologics were stopped and switched. Most patients had an improvement in their PASI scores after 2 to 4 weeks of starting the biologic and had a PASI 90 score improvement. All patients had more than a 5 point improvement in DLQI score. Discussion: Biologic use in our department is on the increase. Our patients had considerable improvements in their PASI and DLQI scores. Secondary failures have occurred usually after 2 to 4 years and switching has yielded positive results. Biologics are expensive drugs and recently we have switched to cheaper biosimilars. Doctors should be aware of the treatment options available for psoriasis patients, their possible side effects and when to refer to our department. In most cases a satisfactory response can be achieved.peer-reviewe

Pilot study of the safety and effect of adalimumab on pain, physical function, and musculoskeletal disease in mucopolysaccharidosis types I and II.

Mucopolysaccharidosis I and II are lysosomal storage disorders that, despite treatment with hematopoietic cell transplantation (HCT) and/or enzyme replacement therapy (ERT), continue to cause significant skeletal abnormalities leading to pain, stiffness, physical dysfunction, and short stature. Tumor necrosis factor - alpha (TNF-α) is elevated in individuals with MPS I and II and associated with pain and physical dysfunction. Therefore, we evaluated the safety and effects of the TNF-α inhibitor adalimumab in patients with MPS I and II in a 32-week, randomized, double blind, placebo-controlled, crossover study of adalimumab at a dose of 20&nbsp;mg (weight 15-&lt;30&nbsp;kg) or 40&nbsp;mg (weight ≥&nbsp;30&nbsp;kg) administered subcutaneously every other week or saline placebo for 16&nbsp;weeks. Participants were evaluated at baseline, week 16, and week 32 with the Children's Health Questionnaire - Parent Form 50 (CHQ-PF50), the Pediatric Pain Questionnaire (PPQ), range-of-motion (ROM) measurements, anthropometry, six-minute walk test (6MWT), hand dynamometer, and laboratory evaluations for safety. The primary outcome was safety and primary efficacy outcome was bodily pain (BP) measured by the CHQ-PF50. Two subjects, one with MPS I and one with MPS II, completed the study. Adalimumab was well tolerated and there were no serious adverse events. Standardized BP scores for age and gender were higher (i.e. less pain) at the end of the treatment versus placebo phase for both subjects. Subject #1 became unblinded during treatment due to skin erythema. Behavior measured by both CHQ-PF50 and parental report improved during treatment compared to placebo in both subjects. ROM improved by &gt;&nbsp;5° in seven of eight joints in Subject #1 and five of eight joints in Subject #2 (range 7.0° to 52.8°). There was no change in the PPQ, 6MWT, or hand dynamometer. Data from this small pilot study suggest that treatment with adalimumab is safe, tolerable, and may improve ROM, physical function, and possibly pain, in children with MPS I or II. However, additional clinical trials are needed before this therapy should be recommended as part of clinical care