Biologic Response Modifiers (BRMs)

Article Author:
Binita Sapkota
Shah Makandar

Article Editor:
Saurav Acharya

Editors In Chief:
Sisira Reddy
Dhia Kaffel
Joseph Nahas

Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes

7/14/2019 4:40:44 PM


Biologic response modifiers (BRMs), also known as immunomodulator or cytokine inhibitors, are naturally occurring substances in our body that can also be manufactured in the laboratory. Autoimmune diseases incur a substantial economic burden to the patients and society. BRMs target the disease-causing mechanism and have now become revolutionary in the treatment of many autoimmune phenomena. Unsatisfactory response or evidence of disease progression despite treatment with conventional therapy mandates the use of BRM alone or in combination with traditional therapy.[1] For example, tumor necrosis factor (TNF) inhibitors, in combination with methotrexate, were superior to either methotrexate or a TNF inhibitor alone in patients with rheumatoid arthritis (RA) resistant to initial therapy.[2] Combination of a biologic agent and an immunomodulator is commonly used to induce and maintain remission in patients with moderate to severe Crohn disease.[3] BRMs are also recommended as first-line therapy for severe psoriatic arthritis who already have erosive changes and functional limitations. Patients with axial ankylosing spondylitis (AS) who have very high disease activity, defined as a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) more than or equal to four and patients with peripheral AS with concomitant moderate to severe psoriasis, inflammatory bowel disease or flares of anterior uveitis also benefit from BRMs.[4] Anakinra used as initial therapy in patients with systemic juvenile idiopathic arthritis (JIA) resulted in rapid symptom relief and also prevented chronic arthritis.[5] 

Knowing the fact that TNF-alpha, interleukin (IL)-17, IL-1 are vital mediators of graft versus host disease,[6] BRMs have been used to prevent and treat GVHD.[7] BRMs are also therapeutic in various cancers of the lung, head, neck, skin, kidneys, bladder, and hematologic malignancies. Biologics targeting programmed cell death protein (PD-1), e.g., pembrolizumab and nivolumab have been emerging as a newer treatment modality for melanoma, renal cell cancer, non-squamous lung cancer, lymphoma, and gastrointestinal cancers.[8] BRMs are also found to be effective in secondary amyloidosis in patients with RA and AS.[9] Biologics targeting IL-5 have been emerging in the treatment of severe hyper eosinophilic asthma.[10]

TNF inhibitors, e.g., infliximab, etanercept, adalimumab, certolizumab, and golimumab has been FDA approved for use in RA, ulcerative colitis (UC), Crohn disease (CD), AS, JIA, plaque psoriasis and, psoriatic arthritis. Adalimumab also has approval for hidradenitis suppurativa and uveitis. Non-FDA-approved indications include pyoderma gangrenosum, pustular psoriasis, and GVHD(etanercept). Interleukin-1 inhibitor, e.g., anakinra is FDA approved for RA and neonatal-onset multisystem inflammatory disease. IL-2 inhibitor, e.g., aldesleukin, is used in metastatic renal cell carcinoma and melanoma. Tocilizumab is interleukin-6 inhibitor used in giant cell arteritis, JIA, and RA. Secukinumab that targets interleukin-17 is FDA approved for psoriasis (plaque and arthritis), and AS. Ustekinumab blocks interleukin 12/23 and has been FDA-approved for plaque psoriasis, psoriatic arthritis, and CD. Abatacept (T-cell co-stimulation blocker) has approval for use in RA, JIA and Psoriatic arthritis. Rituximab is FDA approved for chronic lymphocytic leukemia, non-Hodgkins lymphoma, RA, granulomatous polyangiitis, and pemphigus vulgaris. Off label uses include Burkitt lymphoma, CNS lymphoma, GVHD, lupus nephritis, and Hodgkin lymphoma. Tofacitinib is Janus kinase (JAK) inhibitors indicated for psoriatic arthritis, RA, and UC.[11]

Mechanism of Action

CD4-T cells can differentiate into T helper cells Th1 and Th2. Th1 cells participate in cell-mediated inflammation by producing Interferon gamma, TNF, and IL 2 that target intracellular pathogens. Th2 cells participate in humoral immunity that stimulates antibody production by B cells to produce IL-4, IL-5, IL-10, and IL-13 that target extracellular pathogens. These cytokines are involved in the mediation of inflammatory response, infection, autoimmunity, transplant rejection, and GVHD.[12] Biologic response modifiers modulate the immune response by either interfering the effect of these cytokines,[13] inhibiting costimulation of T cell activation,[14] depleting/inhibiting B cells.[15] JAK inhibitors target at the intracellular level by blocking the cellular signaling pathway. 


Biologic response modifier therapy is administered either by Intravenous (IV) or subcutaneous (SC) route. IV is usually done in the hospital or outpatient setting while SC is generally self-administered by patients or by health care professionals.[16] The administration could be weekly, biweekly, monthly, or bimonthly depending on the indication and half-life of the medication. Infliximab, sarilumab, tocilizumab, secukinumab, rituximab, and abatacept administration is intravenous. Adalimumab, golimumab, etanercept, certolizumab, anakinra, and ustekinumab administration is subcutaneous. Abatacept, tocilizumab, and golimumab can be given either SC or IV, and tofacitinib dosing is oral.[17] 

Adverse Effects

The adverse effects of biologic response modifier therapy could be secondary to stimulation, suppression, or disruption of immune homeostasis.[18] Immune stimulation causing activation of various immune cells including macrophages, monocytes, lymphocytes and natural killer cells leads to massive release of cytokines including IL1, TNF alfa, INF gamma, IL 6 and IL 8 that often cause symptoms such as fever, chills, muscle aches, weakness, loss of appetite, nausea, vomiting, diarrhea and skin rash.[19] 

Since T cell-mediated response is involved in the destruction of pathogens, inhibition of immune response by BRM increases the risk of asymptomatic to life-threatening infection due to the virus, bacteria, mycobacteria, fungi, and protozoa.[20][21] Infection risk is increased, notably in patients with advanced diseases and those who already have received treatment with other immunosuppressants. Infections include reactivation of hepatitis B, hepatitis C, Mycobacterium tuberculosis (TB), non-mycobacterial TB, Histoplasma, Cryptococcus, Coccidioides, Blastomyces, Pulmonary actinomycosis,[22] Pneumocystis carinii,[23] and CMV. Infections due to West Nile virus, parvovirus B19, influenza, herpes simplex, VZV, Aspergillus, Candida, Listeria,[24] Streptococcus pneumoniae have also been reported.[25] Though severe infection often leads to discontinuation of the drug,[26], the rate of serious infections has been declining recently, likely due to increased vigilance and surveillance associated with the use of these medications.[27] The frequency of adverse events with each of these medications has been observed to be disease-specific. For example, researchers noted that the treatment of AS with TNF inhibitors was associated with a lower rate of serious adverse events compared to the treatment of RA. It could be explained by the fact that RA in itself causes immunosuppression and treatment is often in combination with other DMARD or steroids.[28] 

Multiple biologics also increase the risk of malignancies, such as Hodgkin and non-Hodgkin Lymphoma, leukemia, non-melanoma skin cancer.[29]

Disruption of immune homeostasis causes a paradoxical effect in various tissues leading to autoimmunity. Various BRM has associations with lupus-like syndrome, antiphospholipid syndrome, vasculitis, dermatomyositis, polymyositis, peripheral neuropathy, multiple sclerosis, autoimmune hepatitis, optic neuritis, uveitis, and interstitial lung disease.[30] TNF inhibitors used to treat certain autoimmune diseases was found to exacerbate inflammatory bowel disease,[31] sarcoidosis-like lesions and psoriasis.[32][33] Adalimumab was found to be associated with multiple sclerosis.[34] BRM molecules can also act as an antigen for preformed antibodies in the body, causing anaphylactic reactions.[18] Additionally, infusion reaction can manifest as fever, urticaria, hypotension, and angioedema due to acute hypersensitivity reaction or polyarthritis, and rash due to a delayed hypersensitivity reaction.[35] Injection site reactions manifest as redness, pain, swelling, cutaneous infection, bruising, and itching.[36]


Biologic response modifiers should not be taken by patients who have active infections, demyelinating diseases, e.g., (multiple sclerosis, optic neuritis), and immunodeficiency syndromes. Use of TNF alfa blockers in chronic granulomatous disease associated colitis was found to increase rates of severe infections and even mortality.[37] 

BRM should also be avoided in patients with chronic recurrent infections and untreated latent TB. TNF inhibitors should be avoided or used with caution in a patient with CHF.[38] Evidence is limited for safety during pregnancy and breastfeeding. It is advised to avoid pregnancy or breastfeeding while taking BRMs.[39]


Before starting biologic response modifier therapy, patients should undergo evaluation for latent TB with the past medical history of TB, tuberculin skin test, chest X-ray, and TB interferon. Latent TB should have treatment for nine months, and treatment with BRM should be postponed for one month of treatment completion. This approach has demonstrated to decrease the rate of reactivation of TB.[40] Hepatitis B surface Antigen test, liver function test (LFT), complete blood count (CBC), age-appropriate screening for cancer, pregnancy test, monitoring for contraindications and drug interactions should be done. Age appropriate vaccine status should be updated, e.g., pneumococcal, influenza, and hepatitis B vaccinations.[41] The live vaccine should be given at least 4 weeks before BRM treatment.

All patients taking BRM should have monitoring for both treatment-related efficacy and safety. Patient's symptom relief, physical exam, erythrocyte sedimentation rate, C-reactive protein, autoimmune markers, radiography, CBC, and LFT can be used to monitor efficacy and safety.[42] Treatment should stop if there is no evidence of effectiveness within 3 to 6months of therapy or any evidence of severe side effects or pregnancy. Due to concern for risks of infection, many experts recommend stopping BRMs at least two half-life of particular medication before surgery and resume once wound healing, and no evidence of infection is ensured usually after 1 to 2 weeks.[43]


Biologic response modifiers can often cause bone marrow suppression, hepatotoxicity, cardiopulmonary and renal dysfunction, disseminated intravascular coagulation, and often death. Toxicity is usually due to immune system activation and is manageable by premedication or adjusting dose.[44] 

Enhancing Healthcare Team Outcomes

Early treatment with biologic response modifier improves outcomes and prevents disability related to autoimmune diseases; however, currently, no clinical predictors or biomarkers are available to guide physicians to select BRM for an individual patient. Not all patients with the same illness respond to particular BRM. Genetic polymorphism in the genes encoding the receptors that the BRM targets, affects the efficacy of BRM. Performing genetic tests before starting the treatment may help in choosing a specific BRM for a particular patient.

It is crucial to consider patient-related factors, e.g., patient convenience, local availability, patient's understanding of risks of medication, route, the frequency of administration, and cost-effectiveness while choosing BRM. The patient should be actively involved while choosing and making a treatment decision, and they should be aware of the adverse effects of the medication under consideration.

BRM therapy requires an interprofessional team approach, including physicians, specialists, specialty-trained nurses, and pharmacists, all collaborating across disciplines to achieve optimal patient results. [Level V]

Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Biologic Response Modifiers (BRMs) - Questions

Take a quiz of the questions on this article.

Take Quiz
Biologic response modifiers are usually prescribed for autoimmune diseases if there is evidence of unsatisfactory response or disease progression despite treatment with conventional therapy. Its use has been associated with various side effects. Which one of the following is the most common adverse effect associated with the use of BRMs?

Click Your Answer Below

Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.

Sign Up
A 34-year-old male presents to the clinic for lower back pain and morning stiffness for the last two months. Back pain is worse at night and improved with exercise. An initial blood test was significant for elevated erythrocyte sedimentation rate and C-reactive protein. X-ray of the lumbar spine was unremarkable; however, MRI of the lumbar spine showed erosions and sclerosis at vertebral margins. The patient was diagnosed with ankylosing spondylitis and prescribed infliximab. He was doing well until six months after therapy when he presented with scaly erythematous plaques over the scalp and yellow discoloration of nails. Which of the following most accurately describes the pathophysiology of the patient's new dermatologic finding?

Click Your Answer Below

Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.

Sign Up
A 36-year-old female with moderately severe rheumatoid arthritis follows up in the clinic. Due to an inadequate response, her dose of methotrexate was increased to 25 mg/week nine months ago. Her other home medications include prednisone 10 mg/day, naproxen and folic acid. She still complains of persistent pain and swelling over her bilateral metacarpophalangeal joints and bilateral wrists. She reports morning stiffness over hands for about 45 minutes. Vital signs are within normal limits. Mild tenderness is noted over the affected joints. Plain radiographs of the hands and wrists show periarticular osteopenia and erosions. Complete blood count, basic metabolic panel and liver function tests were unremarkable. Tuberculin test and screening for Hepatitis B were negative. Which of the following is the next best step in the management of this patient?

Click Your Answer Below

Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.

Sign Up

Biologic Response Modifiers (BRMs) - References


Singh JA,Hossain A,Tanjong Ghogomu E,Mudano AS,Tugwell P,Wells GA, Biologic or tofacitinib monotherapy for rheumatoid arthritis in people with traditional disease-modifying anti-rheumatic drug (DMARD) failure: a Cochrane Systematic Review and network meta-analysis (NMA). The Cochrane database of systematic reviews. 2016 Nov 17;     [PubMed]
Cush JJ, Biological drug use: US perspectives on indications and monitoring. Annals of the rheumatic diseases. 2005 Nov;     [PubMed]
Ferraccioli G, [Biologic therapy with anti-TNFα in rheumathoid arthritis]. Reumatismo. 2005;     [PubMed]
Hülsdünker J,Zeiser R, Insights into the pathogenesis of GvHD: what mice can teach us about man. Tissue antigens. 2015 Jan;     [PubMed]
Cutler C,Antin JH, Novel drugs for the prevention and treatment of acute GVHD. Current pharmaceutical design. 2008;     [PubMed]
Voena C,Chiarle R, Advances in cancer immunology and cancer immunotherapy. Discovery medicine. 2016 Feb;     [PubMed]
Pamuk ÖN,Kalyoncu U,Aksu K,Omma A,Pehlivan Y,Çağatay Y,Küçükşahin O,Dönmez S,Çetin GY,Mercan R,Bayındır Ö,Çefle A,Yıldız F,Balkarlı A,Kılıç L,Çakır N,Kısacık B,Öksüz MF,Çobankara V,Onat AM,Sayarlıoğlu M,Öztürk MA,Pamuk GE,Akkoç N, A multicenter report of biologic agents for the treatment of secondary amyloidosis in Turkish rheumatoid arthritis and ankylosing spondylitis patients. Rheumatology international. 2016 Jul;     [PubMed]
Mukherjee M,Sehmi R,Nair P, Anti-IL5 therapy for asthma and beyond. The World Allergy Organization journal. 2014;     [PubMed]
Davis BP,Ballas ZK, Biologic response modifiers: Indications, implications, and insights. The Journal of allergy and clinical immunology. 2017 May;     [PubMed]
Mosmann TR,Moore KW, The role of IL-10 in crossregulation of TH1 and TH2 responses. Immunology today. 1991 Mar;     [PubMed]
Dilek N,Poirier N,Hulin P,Coulon F,Mary C,Ville S,Vie H,Clémenceau B,Blancho G,Vanhove B, Targeting CD28, CTLA-4 and PD-L1 costimulation differentially controls immune synapses and function of human regulatory and conventional T-cells. PloS one. 2013;     [PubMed]
Rein P,Mueller RB, Treatment with Biologicals in Rheumatoid Arthritis: An Overview. Rheumatology and therapy. 2017 Dec;     [PubMed]
Bendtzen K,Hansen MB,Ross C,Poulsen LK,Svenson M, Cytokines and autoantibodies to cytokines. Stem cells (Dayton, Ohio). 1995 May;     [PubMed]
Anselmo AC,Gokarn Y,Mitragotri S, Non-invasive delivery strategies for biologics. Nature reviews. Drug discovery. 2018 Nov 30;     [PubMed]
Dowty ME,Lin J,Ryder TF,Wang W,Walker GS,Vaz A,Chan GL,Krishnaswami S,Prakash C, The pharmacokinetics, metabolism, and clearance mechanisms of tofacitinib, a janus kinase inhibitor, in humans. Drug metabolism and disposition: the biological fate of chemicals. 2014 Apr;     [PubMed]
Descotes J, Immunotoxicity of monoclonal antibodies. mAbs. 2009 Mar-Apr;     [PubMed]
Wing M, Monoclonal antibody first dose cytokine release syndromes-mechanisms and prediction. Journal of immunotoxicology. 2008 Jan;     [PubMed]
Browne SK,Holland SM, Immunodeficiency secondary to anticytokine autoantibodies. Current opinion in allergy and clinical immunology. 2010 Dec;     [PubMed]
Wallis RS, Infectious complications of tumor necrosis factor blockade. Current opinion in infectious diseases. 2009 Aug;     [PubMed]
Cohen R,Bowie W,Enns R,Flint J,Fitzgerald M, Pulmonary actinomycosis complicating infliximab therapy for Crohn disease. BMJ case reports. 2009;     [PubMed]
Kaur N,Mahl TC, Pneumocystis jiroveci (carinii) pneumonia after infliximab therapy: a review of 84 cases. Digestive diseases and sciences. 2007 Jun;     [PubMed]
Kelesidis T,Salhotra A,Fleisher J,Uslan DZ, Listeria endocarditis in a patient with psoriatic arthritis on infliximab: are biologic agents as treatment for inflammatory arthritis increasing the incidence of Listeria infections? The Journal of infection. 2010 May;     [PubMed]
Le Saux N, Biologic response modifiers to decrease inflammation: Focus on infection risks. Paediatrics     [PubMed]
Singh JA,Wells GA,Christensen R,Tanjong Ghogomu E,Maxwell L,Macdonald JK,Filippini G,Skoetz N,Francis D,Lopes LC,Guyatt GH,Schmitt J,La Mantia L,Weberschock T,Roos JF,Siebert H,Hershan S,Lunn MP,Tugwell P,Buchbinder R, Adverse effects of biologics: a network meta-analysis and Cochrane overview. The Cochrane database of systematic reviews. 2011 Feb 16;     [PubMed]
Sakai R,Cho SK,Nanki T,Koike R,Watanabe K,Yamazaki H,Nagasawa H,Amano K,Tanaka Y,Sumida T,Ihata A,Yasuda S,Nakajima A,Sugihara T,Tamura N,Fujii T,Dobashi H,Miura Y,Miyasaka N,Harigai M, The risk of serious infection in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors decreased over time: a report from the registry of Japanese rheumatoid arthritis patients on biologics for long-term safety (REAL) database. Rheumatology international. 2014 Dec;     [PubMed]
Fouque-Aubert A,Jette-Paulin L,Combescure C,Basch A,Tebib J,Gossec L, Serious infections in patients with ankylosing spondylitis with and without TNF blockers: a systematic review and meta-analysis of randomised placebo-controlled trials. Annals of the rheumatic diseases. 2010 Oct;     [PubMed]
Lebrec H,Ponce R,Preston BD,Iles J,Born TL,Hooper M, Tumor necrosis factor, tumor necrosis factor inhibition, and cancer risk. Current medical research and opinion. 2015 Mar;     [PubMed]
Perez-Alvarez R,Pérez-de-Lis M,Ramos-Casals M, Biologics-induced autoimmune diseases. Current opinion in rheumatology. 2013 Jan;     [PubMed]
Toussirot É,Houvenagel É,Goëb V,Fouache D,Martin A,Le Dantec P,Dernis E,Wendling D,Ansemant T,Berthelot JM,Bader-Meunier B,Kantelip B, Development of inflammatory bowel disease during anti-TNF-α therapy for inflammatory rheumatic disease: a nationwide series. Joint, bone, spine : revue du rhumatisme. 2012 Oct;     [PubMed]
Nagy G,Lukács K,Sziray A,Fazekas K,Florián A,Tamási L,Károlyi Z, [Adverse events during biological therapy -- focusing on dermatological side-effects]. Orvosi hetilap. 2011 Feb 6;     [PubMed]
Joyau C,Veyrac G,Dixneuf V,Jolliet P, Anti-tumour necrosis factor alpha therapy and increased risk of de novo psoriasis: is it really a paradoxical side effect? Clinical and experimental rheumatology. 2012 Sep-Oct;     [PubMed]
Matsumoto T,Nakamura I,Miura A,Momoyama G,Ito K, New-onset multiple sclerosis associated with adalimumab treatment in rheumatoid arthritis: a case report and literature review. Clinical rheumatology. 2013 Feb;     [PubMed]
Kerbleski JF,Gottlieb AB, Dermatological complications and safety of anti-TNF treatments. Gut. 2009 Aug;     [PubMed]
Otani IM,Levin AS,Banerji A, Cutaneous Manifestations of Reactions to Biologics. Current allergy and asthma reports. 2018 Feb 21;     [PubMed]
Uzel G,Orange JS,Poliak N,Marciano BE,Heller T,Holland SM, Complications of tumor necrosis factor-α blockade in chronic granulomatous disease-related colitis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2010 Dec 15;     [PubMed]
Kwon HJ,Coté TR,Cuffe MS,Kramer JM,Braun MM, Case reports of heart failure after therapy with a tumor necrosis factor antagonist. Annals of internal medicine. 2003 May 20;     [PubMed]
Pham-Huy A,Sadarangani M,Huang V,Ostensen M,Castillo E,Troster SM,Vaudry W,Nguyen GC,Top KA, From mother to baby: antenatal exposure to monoclonal antibody biologics. Expert review of clinical immunology. 2019 Mar;     [PubMed]
Carmona L,Gómez-Reino JJ,Rodríguez-Valverde V,Montero D,Pascual-Gómez E,Mola EM,Carreño L,Figueroa M, Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists. Arthritis and rheumatism. 2005 Jun;     [PubMed]
Hanson RL,Gannon MJ,Khamo N,Sodhi M,Orr AM,Stubbings J, Improvement in safety monitoring of biologic response modifiers after the implementation of clinical care guidelines by a specialty. Journal of managed care pharmacy : JMCP. 2013 Jan-Feb;     [PubMed]
Del Olmo L,Hernández B,Galindo-Izquierdo M,Tébar D,Balsa A,Carmona L, [Peri-operative management of disease modifying anti-rheumatic drugs: recommendations based on a meta-analysis]. Revista espanola de cirugia ortopedica y traumatologia. 2012 Sep-Oct;     [PubMed]
Gribble EJ,Sivakumar PV,Ponce RA,Hughes SD, Toxicity as a result of immunostimulation by biologics. Expert opinion on drug metabolism     [PubMed]
D'Haens G,Baert F,van Assche G,Caenepeel P,Vergauwe P,Tuynman H,De Vos M,van Deventer S,Stitt L,Donner A,Vermeire S,Van De Mierop FJ,Coche JR,van der Woude J,Ochsenkühn T,van Bodegraven AA,Van Hootegem PP,Lambrecht GL,Mana F,Rutgeerts P,Feagan BG,Hommes D, Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet (London, England). 2008 Feb 23     [PubMed]
Ward MM,Deodhar A,Akl EA,Lui A,Ermann J,Gensler LS,Smith JA,Borenstein D,Hiratzka J,Weiss PF,Inman RD,Majithia V,Haroon N,Maksymowych WP,Joyce J,Clark BM,Colbert RA,Figgie MP,Hallegua DS,Prete PE,Rosenbaum JT,Stebulis JA,van den Bosch F,Yu DT,Miller AS,Reveille JD,Caplan L, American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis. Arthritis & rheumatology (Hoboken, N.J.). 2016 Feb     [PubMed]
Nigrovic PA,Mannion M,Prince FH,Zeft A,Rabinovich CE,van Rossum MA,Cortis E,Pardeo M,Miettunen PM,Janow G,Birmingham J,Eggebeen A,Janssen E,Shulman AI,Son MB,Hong S,Jones K,Ilowite NT,Cron RQ,Higgins GC, Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series. Arthritis and rheumatism. 2011 Feb     [PubMed]


The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Rheumatology. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Rheumatology, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Rheumatology, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Rheumatology. When it is time for the Rheumatology board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Rheumatology.