Baricitinib in Patients with Refractory Rheumatoid Arthritis

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Just published in the N Engl J Med Baricitinib a new jak inhibitor improved outcomes in RA patients who failed to biologics

Genovese M es al. N Engl J Med 2016;374:1243-1252

BACKGROUND

In phase 2 studies, baricitinib, an oral Janus kinase 1 and 2 inhibitor, reduced disease activity in patients with rheumatoid arthritis who had not previously received treatment with biologic disease-modifying antirheumatic drugs (DMARDs).
Full Text of Background…
METHODS
In this phase 3 study involving 527 patients with an inadequate response to or unacceptable side effects associated with one or more tumor necrosis factor inhibitors, other biologic DMARDs, or both, we randomly assigned the patients in a 1:1:1 ratio to baricitinib at a dose of 2 or 4 mg daily or placebo for 24 weeks. End points, tested hierarchically at week 12 to control type 1 error, were the American College of Rheumatology 20% (ACR20) response (primary end point), the Health Assessment Questionnaire–Disability Index (HAQ-DI) score, the 28-joint Disease Activity Score based on C-reactive protein level (DAS28-CRP), and a Simplified Disease Activity Index (SDAI) score of 3.3 or less (on a scale of 0.1 to 86.0, with a score of 3.3 or less indicating remission). Comparisons with placebo were made first with the 4-mg dose of baricitinib and then with the 2-mg dose

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Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis

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Dominique Baeten, M.D., Joachim Sieper, M.D., Jürgen Braun, M.D., Xenofon Baraliakos, M.D., Maxime Dougados, M.D., Paul Emery, F.R.C.P., Atul Deodhar, M.D., Brian Porter, M.D., Ph.D., M.P.H., Ruvie Martin, Ph.D., Mats Andersson, M.Sc., Shephard Mpofu, M.D., and Hanno B. Richards, M.D. for the MEASURE 1 and MEASURE 2 Study Groups
N Engl J Med 2015; 373:2534-2548December 24, 2015DOI: 10.1056/NEJMoa1505066BACKGROUND
Secukinumab is an anti–interleukin-17A monoclonal antibody that has been shown to control the symptoms of ankylosing spondylitis in a phase 2 trial. We conducted two phase 3 trials of secukinumab in patients with active ankylosing spondylitis.
METHODS
In two double-blind trials, we randomly assigned patients to receive secukinumab or placebo. In MEASURE 1, a total of 371 patients received intravenous secukinumab (10 mg per kilogram of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8. In MEASURE 2, a total of 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4. At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg. The primary end point was the proportion of patients with at least 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16.

 

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Use of anti-TNFs for difficult-to-treat urticaria: response to Cooke et al

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Biologics: Targets and Therapy (Open access)

Simon Francis Thomsen1,2 Freja Lærke Sand1,2 1Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark; 2Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

Dear editor We read with interest the recent paper by Cooke et al about the use of biologic agents for intractable urticaria.1 Particularly, the authors reckon that the evidence supporting the use of anti-TNFs is limited by the small numbers of patients in non-controlled studies, often with urticarial disorders not typical of chronic urticaria such as vasculitis and delayed pressure urticaria. However, we want to draw the authors’ and readers’ attention to our report from 2013 about the use of adalimumab and etanercept in 20 patients with chronic urticaria with or without angioedema2 (updated in 2015 with an additional five patients).3 This report is to date the largest series of patients published and adds substantially to the small body of evidence supporting the use of anti-TNFs in subgroups of patients with chronic urticaria unresponsive to conventional therapy or omalizumab. Notably, 60% of our patients obtained complete or almost complete resolution of urticaria and angioedema after onset of therapy with either adalimumab or etanercept, whereas another 15% of our patients experienced partial response to therapy. Some of our patients were previously unresponsive to or experienced side effects from omalizumab. Duration of treatment ranged between 2 and 39 months. We observed side effects in 30% of our patients, particularly mild recurrent upper respiratory infections, whereas one patient experienced severe central nervous system toxicity. We propose that adalimumab and etanercept may be effective in some patients with chronic urticaria who do not respond sufficiently to high-dose antihistamines or in whom other immunosuppressive drugs or omalizumab are ineffective or associated with unacceptable side effects. However, patients should be monitored closely due to the possibility of severe side effects of anti-TNF treatment. We agree that larger randomized controlled trials are needed before a definite recommendation can be made in regards to the use of anti-TNFs for chronic urticaria. Disclosure The authors report no conflict of interest in this communication

Role of biologics in intractable urticaria

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Andrew Cooke,1 Adeeb Bulkhi,1,2 Thomas B Casale1

DOI http://dx.doi.org/10.2147/BTT.S63839

1Department of Internal Medicine, Division of Allergy and Immunology, University of South Florida, Tampa, FL, USA; 2Department of Internal Medicine, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia

Abstract: Chronic urticaria (CU) is a common condition faced by many clinicians. CU has been estimated to affect approximately 0.5%–1% of the population, with nearly 20% of sufferers remaining symptomatic 20 years after onset. Antihistamines are the first-line therapy for CU. Unfortunately, nearly half of these patients will fail this first-line therapy and require other medication, including immune response modifiers or biologics. Recent advances in our understanding of urticarial disorders have led to more targeted therapeutic options for CU and other urticarial diseases. The specific biologic agents most investigated for antihistamine-refractory CU are omalizumab, rituximab, and intravenous immunoglobulin (IVIG). Of these, the anti-IgE monoclonal antibody omalizumab is the best studied, and has recently been approved for the management of CU. Other agents, such as interleukin-1 inhibitors, have proved beneficial for Schnitzler syndrome and cryopyrin-associated periodic syndromes (CAPS), diseases associated with urticaria. This review summarizes the relevant data regarding the efficacy of biologics in antihistamine-refractory CU.

Keywords: chronic urticaria, omalizumab, intravenous immunoglobulin, anakinra, canakinumab

Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis

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Mark Lebwohl, M.D., Bruce Strober, M.D., Ph.D., Alan Menter, M.D., Kenneth Gordon, M.D., Jolanta Weglowska, Dr.Med., Lluis Puig, M.D., Ph.D., Kim Papp, M.D., Ph.D., Lynda Spelman, M.B., B.S., Darryl Toth, M.D., Francisco Kerdel, M.D., April W. Armstrong, M.D., et al..N Engl J Med 2015; 373:1318-1328October 1, 2015DOI: 10.1056/NEJMoa1503824

BACKGROUND

Early clinical studies suggested that the anti–interleukin-17 receptor A monoclonal antibody brodalumab has efficacy in the treatment of psoriasis.

METHODS

In two phase 3 studies (AMAGINE-2 and AMAGINE-3), patients with moderate-to-severe psoriasis were randomly assigned to receive brodalumab (210 mg or 140 mg every 2 weeks), ustekinumab (45 mg for patients with a body weight ≤100 kg and 90 mg for patients >100 kg), or placebo. At week 12, patients receiving brodalumab were randomly assigned again to receive a brodalumab maintenance dose of 210 mg every 2 weeks or 140 mg every 2 weeks, every 4 weeks, or every 8 weeks; patients

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Secukinumab Inhibition of Interleukin-17A in Patients with Psoriatic Arthritis

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Philip J. Mease, M.D., Iain B. McInnes, Ph.D., Bruce Kirkham, M.D., Arthur Kavanaugh, M.D., Proton Rahman, M.D., Désirée van der Heijde, M.D., Ph.D., Robert Landewé, M.D., Ph.D., Peter Nash, M.B., B.S., Luminita Pricop, M.D., Jiacheng Yuan, Ph.D., Hanno B. Richards, M.D., and Shephard Mpofu, M.D. for the FUTURE 1 Study Group N Engl J Med 2015; 373:1329-1339October 1, 2015DOI: 10.1056/NEJMoa1412679

BACKGROUND

In a phase 2 study, the inhibition of the interleukin-17A receptor improved signs and symptoms of psoriatic arthritis. We sought to evaluate the efficacy and safety of secukinumab, an anti–interleukin-17A monoclonal antibody, in such patients.

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Epratuzumab Results Disappointing, but Adalimumab Promising

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The Rheumatologist

August 19, 2015 • By

Epratuzumab is a monoclonal antibody targeting CD22, which modulates B cells. Epratuzumab is thought to bind to CD22, resulting in diminishedsystemic lupus erythematosus (SLE)–related hyperactivity of B cells without depleting them.

In each study, patients (n = 786 for EMBODY 1; n = 788 for EMBODY 2) received placebo or treatment with 2,400 mg epratuzumab over four, 12-week treatment cycles administered as 600 mg every week for four weeks or 1,200 mg every two weeks for four weeks. Patients were all receiving corticosteroids at the beginning of the studies, along with either epratuzumab or placebo. Immunosuppressant and antimalarial drugs were given per their standard therapy regimen.

Adalimumab Effective in Juvenile ERA
In other drug news, adalimumab was recently studied in a Phase 3, multicenter, randomized, double-blind trial in patients age 6 years to younger than 18 years withenthesitis-related arthritis (ERA) for 12 weeks (n = 46).2 Patients received 24 mg/m2 adalimumab (maximum dose of 40 mg every other week) or placebo, followed by adalimumab for up to 192 weeks in an open-label design. If a predefined worsening occurred, early escape to the open-label adalimumab treatment period was available at Week 4. Adverse events were evaluated throughout the study. The primary endpoint was the percentage change from baseline at Week 12 in the number of active joints with arthritis (AJC). At baseline, the mean patient age was 12.9 years, with a mean duration of ERA symptoms being 2.6 years. The mean AJC was 7.8 and the mean enthesitis count was 8.1.

At Week 12, there was a 63% reduction in the number of joints with active disease in the adalimumab-treated patients compared with placebo-treated patients (12% reduction). By Week 52, there was an 89% reduction from baseline in the number of joints with active disease. (All patients had been receiving adalimumab after Week 12.) By Week 52, 35% of patients had stopped taking non-steroidal antiinflammatory drugs, 15% had stopped taking corticosteroids, and 11% were no longer taking other disease modifying antirheumatic drugs (e.g., sulfasalazine or methotrexate).

The most common adverse effects were upper respiratory infections, injection site pain, gastroenteritis, ALT elevations, abdominal pain nausea and syncope. Serious adverse events included worsening of ERA and appendicitis.

Michele B. Kaufman, PharmD, CGP, RPh, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

References

  1. UCB. News release: UCB announces Phase 3 clinical trial program for epratuzumab in systemic lupus erythematosus did not meet primary endpoint. 2015 July 28.
  2. Burgos-Varga R, Tse SML, Horneff G, et al. Adalimumab in pediatric enthesitis-related arthritis A randomized, double-blind, placebo-controlled, multicenter study of adalimumab in pediatric patients with enthesitis-related arthritis.Arthritis Care Res (Hoboken). 2015 Jul 20. doi: 10.1002/acr.22657. [Epub ahead of print]