DOCSLIB.ORG

Drug Class Review on Targeted Immune Modulators

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Drug Class Review on Targeted Immune Modulators Drug Class Review on Targeted Immune Modulators Final Report December 2005 The purpose of this report is to make available information regarding the comparative effectiveness and safety profiles of different drugs within pharmaceutical classes. Reports are not usage guidelines, nor should they be read as an endorsement of, or recommendation for, any particular drug, use or approach. Oregon Health & Science University does not recommend or endorse any guideline or recommendation developed by users of these reports. Gerald Gartlehner, MD, MPH Richard A. Hansen, PhD Patricia Thieda, MA Beth Jonas, MD Kathleen N. Lohr, PhD Tim Carey, MD, MPH Produced by RTI-UNC Evidence-based Practice Center Cecil G. Sheps Center for Health Services Research University of North Carolina at Chapel Hill 725 Airport Road, CB# 7590 Chapel Hill, NC 27599-7590 Tim Carey, MD, MPH, Director Oregon Evidence-based Practice Center Mark Helfand, MD, MPH, Director Copyright © 2005 by Oregon Health & Science University Portland, Oregon 97201. All rights reserved Final Report Drug Effectiveness Review Project TABLE OF CONTENTS List of Abbreviations ............................................................................................................................... 4 Introduction............................................................................................................................................... 6 Scope and Key Questions ............................................................................................................. 12 Methods .................................................................................................................................................... 16 Literature Search........................................................................................................................... 16 Study Selection............................................................................................................................. 16 Data Abstraction........................................................................................................................... 18 Quality Assessment....................................................................................................................... 18 Data Synthesis............................................................................................................................... 19 Results....................................................................................................................................................... 21 Key Question 1 ............................................................................................................................. 21 Rheumatoid Arthritis................................................................................................................. 21 Juvenile Rheumatoid Arthritis ................................................................................................... 36 Ankylosing Spondylitis.............................................................................................................. 40 Psoriatic Arthritis....................................................................................................................... 45 Crohn’s Disease......................................................................................................................... 50 Key Question 2- Adverse events................................................................................................... 59 Key Question 3- Subgroups .......................................................................................................... 71 Conclusions.............................................................................................................................................. 76 In-text Tables Table 1: Targeted Immune Modulators .......................................................................................... 6 Table 2: Recommended Dosage and Administration...................................................................... 8 Table 3: Criteria for the Classification of RA.................................................................................9 Table 4: Outcome Measures and Study Eligibility Criteria .......................................................... 14 Table 5: Adjusted Indirect Comparisons of TIMs for Treatment of RA ...................................... 25 Table 6: Summary of Efficacy Trials in Adult Patients with RA ................................................. 32 Table 7: Summary of Efficacy Trials in Patients with JRA.......................................................... 39 Table 8: Summary of Efficacy Trials in Adult Patients with AS.................................................. 43 Table 9: Summary of Efficacy Trials in Adult Patients with PsA ................................................ 48 Table 10: Summary of Efficacy Trials in Adult Patients with Crohn’s Disease........................... 55 Table 11: Summary of Studies Assessing Adverse Events........................................................... 65 Table 12: Summary of Studies Assessing Subgroups................................................................... 74 Table 13: Summary of the Evidence............................................................................................. 78 Figures Figure 1: Adjusted Indirect Comparisons of Anakinra with Anti-TNF Drugs ............................ 26 Figure 2: Results of Literature Search .......................................................................................... 81 Targeted Immune Modulators Page 2 of 332 Final Report Drug Effectiveness Review Project Appendices Appendix A. Search Strategy........................................................................................................ 82 Appendix B. Studies Already Included in Meta-analyses ............................................................ 83 Appendix C. Quality Criteria........................................................................................................ 85 Appendix D. Clinical Assessment Scales Commonly Used in TIMs Trials................................. 87 Appendix E. Study Characteristics, Pooled RRs, and Forest Plots of MAs ................................. 90 Appendix F. Abstract-only Studies (Not Included) ................................................................... 109 Appendix G. Acknowledgements .............................................................................................. 111 Evidence Tables Evidence Table 1: Rheumatoid Arthritis .................................................................................... 113 Evidence Table 2: Juvenile Rheumatoid Arthritis ...................................................................... 172 Evidence Table 3: Ankylosing Spondylitis................................................................................. 178 Evidence Table 4: Psoriatic Arthritis.......................................................................................... 193 Evidence Table 5: Crohn’s Disease ............................................................................................ 208 Evidence Table 6: Adverse Events. ............................................................................................ 235 Evidence Table 7: Subgroups. .................................................................................................... 307 References .............................................................................................................................................. 325 Targeted Immune Modulators Page 3 of 332 Final Report Drug Effectiveness Review Project List of Abbreviations ACR20/50/70 American College of Rheumatology, numbers refer to percentage improvement ADA adalimumab AKA anakinra ANA anti-nuclear antibodies anti-ds DNA antibodies to double-stranded DNA anti-TNF antibodies against tumor necrosis factor AS ankylosing spondylitis ASA Assessment in Ankylosing Spondylitis ASAS20 ASA 20% improvement ASAS50 ASA 50% improvement ASAS70 ASA 70% improvement ASHI arthritis-specific health index BASDAI Bath AS Disease Activity Index BASFI Bath Ankylosing Spondylitis Functional Index BASMI Bath Ankylosing Spondylitis Metrology Index CAHP Childhood Arthritis Health Profile CDAI Crohn’s Disease Activity Index CDEIS Crohn’s Disease Endoscopy Index of Severity CDER Center for Drug Evaluation Research CHAQ Childhood Health Assessment Questionnaire CHF congestive heart failure CHQ Childhood Health Questionnaire CI confidence interval CRP C-reactive protein DAS disease activity score DMARD disease-modifying antirheumatic drug ESR eyrthrocyte sedimentation rate ETA etanercept EULAR European League Against Rheumatism FDA Food and Drug Administration HAQ Health Assessment Questionnaire HAQ-DI Disability Index of the Health Assessment Questionnaire HQL health-related quality of life IgG immunoglobulin G IgM immunoglobulin M IL interleukin INF infliximab ISR injection site reaction ITT intention to treat JIA juvenile idiopathic arthritis JRA juvenile rheumatoid arthritis JCA juvenile chronic arthritis LFT liver function test LOCF last observation carried forward MTX methotrexate N/A not applicable NICE National Institute for Clinical Excellence Targeted Immune Modulators Page 4 of 332 Final Report Drug Effectiveness Review Project NNT number needed to treat NR not reported NSAID non-steroidal anti-inflammatory drug OR odds ratio PASI Psoriasis Area and Severity Index PsA
Load more

Recommended publications
  • Advances in Immunosuppression for Renal Transplantation Antoine Durrbach, Helene Francois, Severine Beaudreuil, Antoine Jacquet and Bernard Charpentier
    REVIEWS Advances in immunosuppression for renal transplantation Antoine Durrbach, Helene Francois, Severine Beaudreuil, Antoine Jacquet and Bernard Charpentier Abstract | The development of immunosuppressants with minimal adverse and nephrotoxic effects is important to improve outcomes, such as acute and chronic antibody-mediated rejection, after organ transplantation. In addition, the application of expanded criteria for donors and transplantation in immunized patients necessitates the development of new therapies. Drug development over the past 10 years has generally been disappointing, but several new promising compounds have been or are being developed to prevent acute and chronic transplant rejection. In this Review, we report on several compounds that have been developed to remove allogenic T cells and/or to inhibit T-cell activation. We also discuss compounds that interfere with antibody-mediated rejection. Durrbach, A. et al. Nat. Rev. Nephrol. 6, 160–167 (2010); published online 2 February 2010; doi:10.1038/nrneph.2009.233 Introduction Renal transplantation has specific features that make or as a result of previous transplantation, has increased it different from transplantation procedures for other over the past decade. In addition, ABO­incompatible organs. For example, outcomes can be affected by grafts are becoming more frequently used. Together, these common states, such as donor and/or recipient age, high factors have led to a rise in the number of ‘immuno logically blood pressure, diabetes mellitus, metabolic disturbances at­risk’ kidney transplantations. Few immunosuppressants (such as high LDL cholesterol) and abnormalities in fluid targeted to B cells have, however, been available to control and electrolyte balance. The kidney is also very sensitive the antibody­mediated response.
    [Show full text]
  • Biologic Armamentarium in Psoriasis
    Vol 9, Issue 1, 2016 ISSN - 0974-2441 Review Article BIOLOGIC ARMAMENTARIUM IN PSORIASIS GANESH PAI1*, NITHIN SASHIDHARAN2 1Medical Director, Derma-Care ‘The Trade Centre’, Mangalore - 575 003, Karnataka, India. 2Consultant Clinical Pharmacologist, Derma-Care ‘The Trade Centre’, Mangalore - 575 003, Karnataka, India. Email: [email protected] Received: 14 July 2015, Revised and Accepted: 24 August 2015 ABSTRACT Psoriasis is an autoimmune disease and further classed as a chronic inflammatory skin condition serving as a global burden. A moderate to severe psoriasis can be treated with conventional therapies. Less efficacy, poor patient compliance, and toxicity issues were the major problems associated with conventional therapies. The introduction of biologic therapy has a great impression on psoriatic treatment duration and enhanced quality of life in psoriasis patients. The new biologic therapies are tailor-made medications with the goal of more specific and effective treatment; less toxicity. The biologic therapy is aimed to target antigen presentation and co-stimulation, T-cell activation, and leukocyte adhesion; and pro-inflammatory cascade. They act as effective and safer substitute to traditional therapy. Secukinumab, certolizumab, itolizumab, golimumab, ustekinumab, adalimumab, infliximab etanercept, alefacept, etc. are the approved biologic with the global market. This review briefs about psoriasis pathogenesis, traditional treatments, and biologic therapies potential. Keywords: Psoriasis, Biologic, Non-biologic treatment. INTRODUCTION migration, potentiation of Th1 type of response, angiogenesis, and epidermal hyperplasia [7]. Psoriasis is an autoimmune disease and further classed as a chronic inflammatory skin condition with prevalence ranging 1-3% in the TNF- is plays vital role in the pathogenesis of psoriasis. It acts by world [1].
    [Show full text]
  • Selective Mtorc2 Inhibitor Therapeutically Blocks Breast Cancer Cell Growth and Survival
    Author Manuscript Published OnlineFirst on January 22, 2018; DOI: 10.1158/0008-5472.CAN-17-2388 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Selective mTORC2 inhibitor therapeutically blocks breast cancer cell growth and survival Thomas A. Werfel1, 3, Shan Wang2, Meredith A. Jackson1, Taylor E. Kavanaugh1, Meghan Morrison Joly3, Linus H. Lee1, Donna J. Hicks3, Violeta Sanchez4, Paula Gonzalez Ericsson4, Kameron V. Kilchrist1, Somtochukwu C. Dimobi1, Samantha M. Sarett1, Dana Brantley-Sieders2, Rebecca S. Cook1,3,4* and Craig L. Duvall1* 1Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232 USA 2Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232.USA 3Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232 USA 4Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232 USA Running Title: A selective mTORC2 inhibitor blocks breast cancer growth Key Words: Breast Cancer, mTOR, Rictor, RNA interference, Nanomedicine *To whom correspondence should be addressed: Craig L. Duvall, PhD Vanderbilt University School of Engineering Department of Biomedical Engineering Nashville, TN 37232 Phone: (615) 322-3598 Fax: (615) 343-7919 Email: [email protected] Rebecca S. Cook, PhD Vanderbilt University Medical Center Department of Cancer Biology Nashville, TN 37232 Phone: (615) 936-3813 Fax: (615) 936-3811 Email: [email protected] Funding. This work was supported by Specialized Program of Research Excellence (SPORE) grant NIH P50 CA098131 (VICC), Cancer Center Support grant NIH P30 CA68485 (VICC), NIH F31 CA195989-01 (MMW), NIH R01 EB019409, DOD CDMRP OR130302, NSF GFRP 1445197, and CTSA UL1TR000445 from the National Center for Advancing Translational Sciences.
    [Show full text]
  • Leflunomide-Arava-Fact-Sheet
    Leflunomide PATIENT FACT SHEET (Arava) Leflunomide (Arava) is a drug approved to treat combination with other DMARDs. Leflunomide blocks the adults with moderate to severe rheumatoid arthritis. formation of DNA, which is important for replicating cells, It belongs to a class of medications called disease such as those in the immune system. It suppresses the modifying antirheumatic drugs (DMARDs). Leflunomide immune system to reduce inflammation that causes pain is often used to treat rheumatoid arthritis alone or in and swelling in rheumatoid arthritis. WHAT IS IT? Leflunomide is usually given as a 20 mg tablet once a the first 3 days after starting leflunomide. It may take day. Doctors will often prescribe a “loading dose” to be several weeks after starting leflunomide to experience an taken when the medicine is first prescribed. The loading improvement in joint pain or swelling. Complete benefits dose of leflunomide is usually 100 mg (or five 20 mg may not be experienced until 6 to 12 weeks after starting HOW TO tablets) once weekly for 3 weeks or 100 mg a day for the medication. TAKE IT The most common side effect of leflunomide is stomach pain, indigestion, rash, and hair loss. In fewer diarrhea, which occurs in approximately 20 percent than 10 percent of patients, leflunomide can cause of patients. This symptom frequently improves with abnormal liver function tests or decreased blood cell time or by taking a medication to prevent diarrhea. If or platelet counts. Rarely, this drug may cause lung diarrhea persists, the dose of leflunomide may need to problems, such as cough, shortness of breath or be reduced.
    [Show full text]
  • 2017 American College of Rheumatology/American Association
    Arthritis Care & Research Vol. 69, No. 8, August 2017, pp 1111–1124 DOI 10.1002/acr.23274 VC 2017, American College of Rheumatology SPECIAL ARTICLE 2017 American College of Rheumatology/ American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty SUSAN M. GOODMAN,1 BRYAN SPRINGER,2 GORDON GUYATT,3 MATTHEW P. ABDEL,4 VINOD DASA,5 MICHAEL GEORGE,6 ORA GEWURZ-SINGER,7 JON T. GILES,8 BEVERLY JOHNSON,9 STEVE LEE,10 LISA A. MANDL,1 MICHAEL A. MONT,11 PETER SCULCO,1 SCOTT SPORER,12 LOUIS STRYKER,13 MARAT TURGUNBAEV,14 BARRY BRAUSE,1 ANTONIA F. CHEN,15 JEREMY GILILLAND,16 MARK GOODMAN,17 ARLENE HURLEY-ROSENBLATT,18 KYRIAKOS KIROU,1 ELENA LOSINA,19 RONALD MacKENZIE,1 KALEB MICHAUD,20 TED MIKULS,21 LINDA RUSSELL,1 22 14 23 17 ALEXANDER SAH, AMY S. MILLER, JASVINDER A. SINGH, AND ADOLPH YATES Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient. The ACR considers adherence to the recommendations within this guideline to be volun- tary, with the ultimate determination regarding their application to be made by the physician in light of each patient’s individual circumstances. Guidelines and recommendations are intended to promote benefi- cial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed and endorsed by the ACR are subject to periodic revision as warranted by the evolution of medi- cal knowledge, technology, and practice.
    [Show full text]
  • Angiotensin-Converting Enzyme (ACE) Inhibitors Single Entity Agents
    Therapeutic Class Overview Angiotensin-Converting Enzyme (ACE) Inhibitors Single Entity Agents Therapeutic Class Overview/Summary: The renin-angiotensin-aldosterone system (RAAS) is the most important component in the homeostatic regulation of blood pressure.1,2 Excessive activity of the RAAS may lead to hypertension and disorders of fluid and electrolyte imbalance.3 Renin catalyzes the conversion of angiotensinogen to angiotensin I. Angiotensin I is then cleaved to angiotensin II by angiotensin- converting enzyme (ACE). Angiotensin II may also be generated through other pathways (angiotensin I convertase).1 Angiotensin II can increase blood pressure by direct vasoconstriction and through actions on the brain and autonomic nervous system.1,3 In addition, angiotensin II stimulates aldosterone synthesis from the adrenal cortex, leading to sodium and water reabsorption. Angiotensin II exerts other detrimental cardiovascular effects including ventricular hypertrophy, remodeling and myocyte apoptosis.1,2 The ACE inhibitors block the conversion of angiotensin I to angiotensin II, and also inhibit the breakdown of bradykinin, a potent vasodilator.4 Evidence-based guidelines recognize the important role that ACE inhibitors play in the treatment of hypertension and other cardiovascular and renal diseases. With the exception of Epaned® (enalapril solution) and Qbrelis® (lisinopril solution), all of the ACE inhibitors are available generically. Table 1. Current Medications Available in Therapeutic Class5-19 Generic Food and Drug Administration
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2017/0209462 A1 Bilotti Et Al
    US 20170209462A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2017/0209462 A1 Bilotti et al. (43) Pub. Date: Jul. 27, 2017 (54) BTK INHIBITOR COMBINATIONS FOR Publication Classification TREATING MULTIPLE MYELOMA (51) Int. Cl. (71) Applicant: Pharmacyclics LLC, Sunnyvale, CA A 6LX 3/573 (2006.01) A69/20 (2006.01) (US) A6IR 9/00 (2006.01) (72) Inventors: Elizabeth Bilotti, Sunnyvale, CA (US); A69/48 (2006.01) Thorsten Graef, Los Altos Hills, CA A 6LX 3/59 (2006.01) (US) A63L/454 (2006.01) (52) U.S. Cl. CPC .......... A61 K3I/573 (2013.01); A61K 3 1/519 (21) Appl. No.: 15/252,385 (2013.01); A61 K3I/454 (2013.01); A61 K 9/0053 (2013.01); A61K 9/48 (2013.01); A61 K (22) Filed: Aug. 31, 2016 9/20 (2013.01) (57) ABSTRACT Disclosed herein are pharmaceutical combinations, dosing Related U.S. Application Data regimen, and methods of administering a combination of a (60) Provisional application No. 62/212.518, filed on Aug. BTK inhibitor (e.g., ibrutinib), an immunomodulatory agent, 31, 2015. and a steroid for the treatment of a hematologic malignancy. US 2017/0209462 A1 Jul. 27, 2017 BTK INHIBITOR COMBINATIONS FOR Subject in need thereof comprising administering pomalido TREATING MULTIPLE MYELOMA mide, ibrutinib, and dexamethasone, wherein pomalido mide, ibrutinib, and dexamethasone are administered con CROSS-REFERENCE TO RELATED currently, simulataneously, and/or co-administered. APPLICATION 0008. In some aspects, provided herein is a method of treating a hematologic malignancy in a subject in need 0001. This application claims the benefit of U.S.
    [Show full text]
  • Heart Failure and Drug-Induced Lupus
    Unusual toxicities with TNF inhibition: Heart failure and drug-induced lupus J.J. Cush John J. Cush, MD, Chief, Rheumatology ABSTRACT demyelinating disease, cytopenias, auto- and Clinical Immunology, Presbyterian Serious and unexpected adverse events, immune disorders, and heart failure. Hospital of Dallas, Clinical Professor of such as heart failure and drug-induced Other essays in this volume address the Internal Medicine, The University of Texas lupus, have been reported in patients subject of infection (10), demyelination Southwestern Medical School, Dallas, Texas, USA. receiving TNF inhibitor therapy. These (11), and lymphoma (12). This review events generally are easily recogniz- will focus on heart failure and lupus- Please address correspondence to: John J. Cush, MD, Presbyterian Hospital able, although they cannot be predicted like disease, which are rarely seen in of Dallas, 8200 Walnut Hill Lane, Dallas, nor avoided, other than by drug avoid- association with TNF inhibitor therapy Texax 75231-4496, USA. ance altogether. Many patients have and are currently without explanation. Clin Exp Rheumatol 2004; 22 (Suppl. 35): great benefit from anti-TNF therapies. S141-S147. Their intelligent use requires a firm Sources of data © Copyright CLINICAL AND EXPERIMENTAL understanding of these rare toxicities, As a consequence of drug approval, RHEUMATOLOGY 2004. so as to minimize the morbidity associ- manufacturers have a responsibility to ated with their uncommon occurrence. collect safety data actively and report Key words: TNF inhibitors, conges- these data to the appropriate agencies. tive heart failure, drug-induced lupus, Introduction For example, in the USA a manufactur- rheumatoid arthritis. The introduction of biologic agents to er must submit periodic safety reports specifically inhibit the pro-inflammato- to the FDA twice yearly (March and ry cytokine, tumor necrosis factor (TNF), September).
    [Show full text]
  • [Product Monograph Template
    PRODUCT MONOGRAPH PrXELJANZ® tofacitinib, tablets, oral 5 mg tofacitinib (as tofacitinib citrate) 10 mg tofacitinib (as tofacitinib citrate) PrXELJANZ® XR tofacitinib extended-release, tablets, oral 11 mg tofacitinib (as tofacitinib citrate) ATC Code: L04AA29 Selective Immunosuppressant Pfizer Canada ULC Date of Preparation: 17,300 Trans-Canada Highway October 24, 2019 Kirkland, Quebec H9J 2M5 TMPF PRISM C.V. c/o Pfizer Manufacturing Holdings LLC Pfizer Canada ULC, Licensee © Pfizer Canada ULC 2019 Submission Control No: 230976 XELJANZ/XELJANZ XR Page 1 of 80 Table of Contents PART I: HEALTH PROFESSIONAL INFORMATION.........................................................3 SUMMARY PRODUCT INFORMATION ........................................................................3 INDICATIONS AND CLINICAL USE..............................................................................3 CONTRAINDICATIONS ...................................................................................................4 ADVERSE REACTIONS..................................................................................................15 DRUG INTERACTIONS ..................................................................................................29 DOSAGE AND ADMINISTRATION..............................................................................34 OVERDOSAGE ................................................................................................................38 ACTION AND CLINICAL PHARMACOLOGY ............................................................38
    [Show full text]
  • Challenges and Approaches for the Development of Safer Immunomodulatory Biologics
    REVIEWS Challenges and approaches for the development of safer immunomodulatory biologics Jean G. Sathish1*, Swaminathan Sethu1*, Marie-Christine Bielsky2, Lolke de Haan3, Neil S. French1, Karthik Govindappa1, James Green4, Christopher E. M. Griffiths5, Stephen Holgate6, David Jones2, Ian Kimber7, Jonathan Moggs8, Dean J. Naisbitt1, Munir Pirmohamed1, Gabriele Reichmann9, Jennifer Sims10, Meena Subramanyam11, Marque D. Todd12, Jan Willem Van Der Laan13, Richard J. Weaver14 and B. Kevin Park1 Abstract | Immunomodulatory biologics, which render their therapeutic effects by modulating or harnessing immune responses, have proven their therapeutic utility in several complex conditions including cancer and autoimmune diseases. However, unwanted adverse reactions — including serious infections, malignancy, cytokine release syndrome, anaphylaxis and hypersensitivity as well as immunogenicity — pose a challenge to the development of new (and safer) immunomodulatory biologics. In this article, we assess the safety issues associated with immunomodulatory biologics and discuss the current approaches for predicting and mitigating adverse reactions associated with their use. We also outline how these approaches can inform the development of safer immunomodulatory biologics. Immunomodulatory Biologics currently represent more than 30% of licensed The high specificity of the interactions of immu- biologics pharmaceutical products and have expanded the thera- nomodulatory biologics with their relevant immune Biotechnology-derived peutic options available
    [Show full text]
  • Alefacept for Severe Alopecia Areata a Randomized, Double-Blind, Placebo-Controlled Study
    STUDY Alefacept for Severe Alopecia Areata A Randomized, Double-blind, Placebo-Controlled Study Bruce E. Strober, MD, PhD; Kavita Menon, MD; Amy McMichael, MD; Maria Hordinsky, MD; Gerald Krueger, MD; Jackie Panko, MD; Kimberly Siu, MD; Jonathan L. Lustgarten, PhD; Elizabeth K. Ross, MD; Jerry Shapiro, MD Objective: To assess the efficacy of alefacept for the treat- istration–approved T-cell biologic inhibitor for the treat- ment of severe alopecia areata (AA). ment of moderate to severe plaque psoriasis. Design: Multicenter, double-blind, randomized, placebo- Main Outcome Measure: Improved Severity of Alo- controlled clinical trial. pecia Tool (SALT) score over 24 weeks. Results: Participants receiving alefacept for 12 consecu- Setting: Academic departments of dermatology in the tive weeks demonstrated no statistically significant im- United States. provement in AA when compared with a well-matched placebo-receiving group (P =.70). Participants: Forty-five individuals with chronic and severe AA affecting 50% to 95% of the scalp hair and re- Conclusion: Alefacept is ineffective for the treatment of sistant to previous therapies. severe AA. Intervention: Alefacept, a US Food and Drug Admin- Arch Dermatol. 2009;145(11):1262-1266 LOPECIA AREATA (AA) IS A lesions of AA are transplanted into mice chronic, potentially revers- with severe combined immunodefi- ible autoimmune skin dis- ciency that lack T lymphocytes, hair ease characterized by non- growth may resume, further confirming scarring patchy hair loss the potential pathogenic role of T lym- Ainvolving any hair-bearing surface.1 Alo- phocytes.8 pecia areata often causes considerable emo- Treatment options for more severe pre- tional distress and has limited treatment sentations of AA are limited, and neither Author Affiliations: options.
    [Show full text]
  • Rheuma.Stamp Line&Box
    Arthritis Mutilans: A Report from the GRAPPA 2012 Annual Meeting Vinod Chandran, Dafna D. Gladman, Philip S. Helliwell, and Björn Gudbjörnsson ABSTRACT. Arthritis mutilans is often described as the most severe form of psoriatic arthritis. However, a widely agreed on definition of the disease has not been developed. At the 2012 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members hoped to agree on a definition of arthritis mutilans and thus facilitate clinical and molecular epidemiological research into the disease. Members discussed the clinical features of arthritis mutilans and defini- tions used by researchers to date; reviewed data from the ClASsification for Psoriatic ARthritis study, the Nordic psoriatic arthritis mutilans study, and the results of a premeeting survey; and participated in breakout group discussions. Through this exercise, GRAPPA members developed a broad consensus on the features of arthritis mutilans, which will help us develop a GRAPPA-endorsed definition of arthritis mutilans. (J Rheumatol 2013;40:1419–22; doi:10.3899/ jrheum.130453) Key Indexing Terms: OSTEOLYSIS ANKYLOSIS PENCIL-IN-CUP SUBLUXATION FLAIL JOINT ARTHRITIS MUTILANS Psoriatic arthritis (PsA) is an inflammatory musculoskeletal gists as a severe destructive form of PsA, a precise disease specifically associated with psoriasis. Moll and definition has not yet been universally accepted. The earliest Wright defined PsA as “psoriasis associated with inflam- definition of arthritis mutilans was provided
    [Show full text]