A Neurologist's Guide to Safe Use of Immunomodulatory Therapies

Ivana Vodopivec; Eli M. Miloslavsky; Camille N. Kotton; Tracey A. Cho

doi:10.1055/s-0034-1390395

Seminars in Neurology, Table of Contents

Semin Neurol 2014; 34(04): 467-478
DOI: 10.1055/s-0034-1390395

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A Neurologist's Guide to Safe Use of Immunomodulatory Therapies

Ivana Vodopivec

¹Harvard Medical School, Boston, Massachusetts

²Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts

,

Eli M. Miloslavsky

¹Harvard Medical School, Boston, Massachusetts

³Rheumatology Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts

,

Camille N. Kotton

¹Harvard Medical School, Boston, Massachusetts

⁴Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts

,

Tracey A. Cho

¹Harvard Medical School, Boston, Massachusetts

²Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts

› Author Affiliations

Abstract

Increased understanding of the pathogenesis of immune-mediated neurologic conditions with concomitant development of new therapeutic agents modulating various aspects of the immune system has resulted in the use of innovative therapies in the treatment of these diseases. These novel immunomodulatory therapeutic regimens also augment the potential for complications, including severe adverse effects.

In this review, the authors address practical issues regarding management of patients with neuroimmunological conditions treated with immunomodulatory therapies, including glucocorticoids, methotrexate, azathioprine, mycophenolate, cyclophosphamide, rituximab, tumor necrosis factor-α inhibitors, and intravenous immunoglobulins. Particular focus is placed on their infectious and noninfectious adverse effects, contraindications, safety monitoring, risk surveillance, and preventive strategies in clinical practice.

Keywords

immunosuppressive drugs - intravenous immunoglobulin - safety - infection - vaccination - glucocorticoid-induced osteoporosis - infertility - malignancy

Full Text

References

References
1 Sarnes E, Crofford L, Watson M, Dennis G, Kan H, Bass D. Incidence and US costs of corticosteroid-associated adverse events: a systematic literature review. Clin Ther 2011; 33 (10) 1413-1432
2 Flossmann O, Berden A, de Groot K , et al; European Vasculitis Study Group. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis 2011; 70 (3) 488-494
3 Wingerchuk DM, Carter JL. Multiple sclerosis: current and emerging disease-modifying therapies and treatment strategies. Mayo Clin Proc 2014; 89 (2) 225-240
4 Rice WR, Singleton FM, Linke MJ, Walzer PD. Regulation of surfactant phosphatidylcholine secretion from alveolar type II cells during Pneumocystis carinii pneumonia in the rat. J Clin Invest 1993; 92 (6) 2778-2782
5 Yale SH, Limper AH. Pneumocystis carinii pneumonia in patients without acquired immunodeficiency syndrome: associated illness and prior corticosteroid therapy. Mayo Clin Proc 1996; 71 (1) 5-13
6 Kadoya A, Okada J, Iikuni Y, Kondo H. Risk factors for Pneumocystis carinii pneumonia in patients with polymyositis/dermatomyositis or systemic lupus erythematosus. J Rheumatol 1996; 23 (7) 1186-1188
7 Komano Y, Harigai M, Koike R , et al. Pneumocystis jiroveci pneumonia in patients with rheumatoid arthritis treated with infliximab: a retrospective review and case-control study of 21 patients. Arthritis Rheum 2009; 61 (3) 305-312
8 Martin-Garrido I, Carmona EM, Specks U, Limper AH. Pneumocystis pneumonia in patients treated with rituximab. Chest 2013; 144 (1) 258-265
9 Ward MM, Donald F. Pneumocystis carinii pneumonia in patients with connective tissue diseases: the role of hospital experience in diagnosis and mortality. Arthritis Rheum 1999; 42 (4) 780-789
10 Rodriguez M, Fishman JA. Prevention of infection due to Pneumocystis spp. in human immunodeficiency virus-negative immunocompromised patients. Clin Microbiol Rev 2004; 17 (4) 770-782 table of contents
11 Thomas Jr CF, Limper AH. Pneumocystis pneumonia. N Engl J Med 2004; 350 (24) 2487-2498
12 Mansharamani NG, Balachandran D, Vernovsky I, Garland R, Koziel H. Peripheral blood CD4 + T-lymphocyte counts during Pneumocystis carinii pneumonia in immunocompromised patients without HIV infection. Chest 2000; 118 (3) 712-720
13 Glück T, Geerdes-Fenge HF, Straub RH , et al. Pneumocystis carinii pneumonia as a complication of immunosuppressive therapy. Infection 2000; 28 (4) 227-230
14 Limper AH, Knox KS, Sarosi GA , et al; American Thoracic Society Fungal Working Group. An official American Thoracic Society statement: treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med 2011; 183 (1) 96-128
15 Godeau B, Coutant-Perronne V, Le Thi Huong D , et al. Pneumocystis carinii pneumonia in the course of connective tissue disease: report of 34 cases. J Rheumatol 1994; 21 (2) 246-251
16 Hwang JP, Lok AS. Management of patients with hepatitis B who require immunosuppressive therapy. Nat Rev Gastroenterol Hepatol 2014; 11 (4) 209-219
17 Vassilopoulos D, Calabrese LH. Management of rheumatic disease with comorbid HBV or HCV infection. Nat Rev Rheumatol 2012; 8 (6) 348-357
18 Mitka M. FDA: Increased HBV reactivation risk with ofatumumab or rituximab. JAMA 2013; 310 (16) 1664
19 Evens AM, Jovanovic BD, Su YC , et al. Rituximab-associated hepatitis B virus (HBV) reactivation in lymphoproliferative diseases: meta-analysis and examination of FDA safety reports. Ann Oncol 2011; 22 (5) 1170-1180
20 Pérez-Alvarez R, Díaz-Lagares C, García-Hernández F , et al; BIOGEAS Study Group. Hepatitis B virus (HBV) reactivation in patients receiving tumor necrosis factor (TNF)-targeted therapy: analysis of 257 cases. Medicine (Baltimore) 2011; 90 (6) 359-371
21 Juan J, Feld JJ. Hepatitis B virus and hepatitis C virus treatment and management in patients receiving immune-modifying agents. Curr Opin Rheumatol 2014; 26 (4) 395-403
22 Flowers MA, Heathcote J, Wanless IR , et al. Fulminant hepatitis as a consequence of reactivation of hepatitis B virus infection after discontinuation of low-dose methotrexate therapy. Ann Intern Med 1990; 112 (5) 381-382
23 Droz N, Gilardin L, Cacoub P , et al. Kinetic profiles and management of hepatitis B virus reactivation in patients with immune-mediated inflammatory diseases. Arthritis Care Res (Hoboken) 2013; 65 (9) 1504-1514
24 Le Boëdec M, Marhadour T, Devauchelle-Pensec V , et al. Baseline laboratory test abnormalities are common in early arthritis but rarely contraindicate methotrexate: study of three cohorts (ESPOIR, VErA, and Brittany). Semin Arthritis Rheum 2013; 42 (5) 474-481
25 Saag KG, Teng GG, Patkar NM , et al; American College of Rheumatology. American College of Rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 2008; 59 (6) 762-784
26 Rubin LG, Levin MJ, Ljungman P , et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis 2014; 58 (3) 309-318
27 Smith BD, Morgan RL, Beckett GA , et al; Centers for Disease Control and Prevention. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rep 2012; 61 (RR-4): 1-32
28 Brunasso AM, Puntoni M, Gulia A, Massone C. Safety of anti-tumour necrosis factor agents in patients with chronic hepatitis C infection: a systematic review. Rheumatology (Oxford) 2011; 50 (9) 1700-1711
29 Gardam MA, Keystone EC, Menzies R , et al. Anti-tumour necrosis factor agents and tuberculosis risk: mechanisms of action and clinical management. Lancet Infect Dis 2003; 3 (3) 148-155
30 Scott DL, Kingsley GH. Tumor necrosis factor inhibitors for rheumatoid arthritis. N Engl J Med 2006; 355 (7) 704-712
31 Brassard P, Kezouh A, Suissa S. Antirheumatic drugs and the risk of tuberculosis. Clin Infect Dis 2006; 43 (6) 717-722
32 Kim HA, Yoo CD, Baek HJ , et al. Mycobacterium tuberculosis infection in a corticosteroid-treated rheumatic disease patient population. Clin Exp Rheumatol 1998; 16 (1) 9-13
33 Furst DE, Keystone EC, Fleischmann R , et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2009. Ann Rheum Dis 2010; 69 (Suppl. 01) i2-i29
34 Singh JA, Furst DE, Bharat A , et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken) 2012; 64 (5) 625-639
35 Latent Tuberculosis Infection. A Guide for Primary Health Care Providers. Available at: http://www.cdc.gov/tb/publications/LTBI/appendixA.htm . Accessed May 25, 2014
36 Smith R, Cattamanchi A, Steingart KR , et al. Interferon-γ release assays for diagnosis of latent tuberculosis infection: evidence in immune-mediated inflammatory disorders. Curr Opin Rheumatol 2011; 23 (4) 377-384
37 Winthrop KL, Weinblatt ME, Daley CL. You can't always get what you want, but if you try sometimes (with two tests—TST and IGRA—for tuberculosis) you get what you need. Ann Rheum Dis 2012; 71 (11) 1757-1760
38 Thomas SL, Hall AJ. What does epidemiology tell us about risk factors for herpes zoster?. Lancet Infect Dis 2004; 4 (1) 26-33
39 Chen SY, Suaya JA, Li Q , et al. Incidence of herpes zoster in patients with altered immune function. Infection 2014; 42 (2) 325-334
40 Zhang J, Xie F, Delzell E , et al. Association between vaccination for herpes zoster and risk of herpes zoster infection among older patients with selected immune-mediated diseases. JAMA 2012; 308 (1) 43-49
41 Yawn BP, Saddier P, Wollan PC, St Sauver JL, Kurland MJ, Sy LS. A population-based study of the incidence and complication rates of herpes zoster before zoster vaccine introduction. Mayo Clin Proc 2007; 82 (11) 1341-1349
42 Harpaz R, Ortega-Sanchez IR, Seward JF ; Advisory Committee on Immunization Practices (ACIP) Centers for Disease Control and Prevention (CDC). Prevention of herpes zoster: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2008; 57 (Suppl. 05) 1-30 , quiz CE2–CE4
43 National Center for Immunization and Respiratory Diseases. General recommendations on immunization — recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2011; 60 (2) 1-64
44 Nagel MA, Cohrs RJ, Mahalingam R , et al. The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features. Neurology 2008; 70 (11) 853-860
45 Nagel MA, Gilden D. Complications of varicella zoster virus reactivation. Curr Treat Options Neurol 2013; 15 (4) 439-453
46 Iordache L, Launay O, Bouchaud O , et al; Associated authors. Autoimmune diseases in HIV-infected patients: 52 cases and literature review. Autoimmun Rev 2014; 13 (8) 850-857
47 Lyons J, Venna N, Cho TA. Atypical nervous system manifestations of HIV. Semin Neurol 2011; 31 (3) 254-265
48 Morar N, Willis-Owen SA, Maurer T, Bunker CB. HIV-associated psoriasis: pathogenesis, clinical features, and management. Lancet Infect Dis 2010; 10 (7) 470-478
49 Branson BM, Handsfield HH, Lampe MA , et al; Centers for Disease Control and Prevention (CDC). Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep 2006; 55 (Suppl. 14) 1-17 , quiz CE1–CE4
50 Shah D, Flanigan T, Lally E. Routine screening for HIV in rheumatology practice. J Clin Rheumatol 2011; 17 (3) 154-156
51 Nguyen BY, Reveille JD. Rheumatic manifestations associated with HIV in the highly active antiretroviral therapy era. Curr Opin Rheumatol 2009; 21 (4) 404-410
52 Yang JJ, Tsai MS, Sun HY , et al. Autoimmune diseases-related arthritis in HIV-infected patients in the era of highly active antiretroviral therapy. J Microbiol Immunol Infect 2013;
53 Keyser FD. Choice of biologic therapy for patients with rheumatoid arthritis: the infection perspective. Curr Rheumatol Rep 2011; 7 (1) 77-87
54 Tan CS, Koralnik IJ. Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis. Lancet Neurol 2010; 9 (4) 425-437
55 Ferenczy MW, Marshall LJ, Nelson CD , et al. Molecular biology, epidemiology, and pathogenesis of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain. Clin Microbiol Rev 2012; 25 (3) 471-506
56 Stolt A, Sasnauskas K, Koskela P, Lehtinen M, Dillner J. Seroepidemiology of the human polyomaviruses. J Gen Virol 2003; 84 (Pt 6) 1499-1504
57 Antonsson A, Green AC, Mallitt KA , et al. Prevalence and stability of antibodies to the BK and JC polyomaviruses: a long-term longitudinal study of Australians. J Gen Virol 2010; 91 (Pt 7) 1849-1853
58 Molloy ES, Calabrese LH. Progressive multifocal leukoencephalopathy associated with immunosuppressive therapy in rheumatic diseases: evolving role of biologic therapies. Arthritis Rheum 2012; 64 (9) 3043-3051
59 Molloy ES. PML and rheumatology: the contribution of disease and drugs. Cleve Clin J Med 2011; 78 (Suppl. 02) S28-S32
60 Bloomgren G, Richman S, Hotermans C , et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med 2012; 366 (20) 1870-1880
61 Neff RT, Hurst FP, Falta EM , et al. Progressive multifocal leukoencephalopathy and use of mycophenolate mofetil after kidney transplantation. Transplantation 2008; 86 (10) 1474-1478
62 Clifford DB, Ances B, Costello C , et al. Rituximab-associated progressive multifocal leukoencephalopathy in rheumatoid arthritis. Arch Neurol 2011; 68 (9) 1156-1164
63 Greaves D, Coggle S, Pollard C, Aliyu SH, Moore EM. Strongyloides stercoralis infection. BMJ 2013; 347: f4610
64 Buonfrate D, Requena-Mendez A, Angheben A , et al. Severe strongyloidiasis: a systematic review of case reports. BMC Infect Dis 2013; 13: 78
65 Bern C, Montgomery SP. An estimate of the burden of Chagas disease in the United States. Clin Infect Dis 2009; 49 (5) e52-e54
66 van Assen S, Agmon-Levin N, Elkayam O , et al. EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis 2011; 70 (3) 414-422
67 van Assen S, Elkayam O, Agmon-Levin N , et al. Vaccination in adult patients with auto-immune inflammatory rheumatic diseases: a systematic literature review for the European League Against Rheumatism evidence-based recommendations for vaccination in adult patients with auto-immune inflammatory rheumatic diseases. Autoimmun Rev 2011; 10 (6) 341-352
68 Centers for Disease Control and Prevention (CDC). Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2012; 61 (40) 816-819
69 Glück T, Müller-Ladner U. Vaccination in patients with chronic rheumatic or autoimmune diseases. Clin Infect Dis 2008; 46 (9) 1459-1465
70 Oren S, Mandelboim M, Braun-Moscovici Y , et al. Vaccination against influenza in patients with rheumatoid arthritis: the effect of rituximab on the humoral response. Ann Rheum Dis 2008; 67 (7) 937-941
71 Bingham III CO, Looney RJ, Deodhar A , et al. Immunization responses in rheumatoid arthritis patients treated with rituximab: results from a controlled clinical trial. Arthritis Rheum 2010; 62 (1) 64-74
72 Papadopoulou D, Sipsas NV. Comparison of national clinical practice guidelines and recommendations on vaccination of adult patients with autoimmune rheumatic diseases. Rheumatol Int 2014; 34 (2) 151-163
73 Kotton CN, Freedman DO. Immunocompromised Travelers (Chapter 8: Advising Travelers With Specific Needs). 2013 . Available at: http://wwwnc.cdc.gov/travel/yellowbook/2014/chapter-8-advising-travelers-with-specific-needs/immunocompromised-travelers . Accessed May 24, 2014
74 Kotton CN, Hibberd PL ; AST Infectious Diseases Community of Practice. Travel medicine and transplant tourism in solid organ transplantation. Am J Transplant 2013; 13 (Suppl. 04) 337-347
75 Weinstein RS. Clinical practice. Glucocorticoid-induced bone disease. N Engl J Med 2011; 365 (1) 62-70
76 Grossman JM, Gordon R, Ranganath VK , et al. American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken) 2010; 62 (11) 1515-1526
77 Homik J, Suarez-Almazor ME, Shea B, Cranney A, Wells G, Tugwell P. Calcium and vitamin D for corticosteroid-induced osteoporosis. Cochrane Database Syst Rev 2000; (2) CD000952
78 Dore RK. Long-term safety, efficacy, and patient acceptability of teriparatide in the management of glucocorticoid-induced osteoporosis. Patient Prefer Adherence 2013; 7: 435-446
79 Saag KG, Shane E, Boonen S , et al. Teriparatide or alendronate in glucocorticoid-induced osteoporosis. N Engl J Med 2007; 357 (20) 2028-2039
80 Rothman MS, West SG, McDermott MT. Osteoporosis for the practicing neurologist. Neurol Clin Pract. 2014; 4 (3) 183-184
81 Haugeberg G, Griffiths B, Sokoll KB, Emery P. Bone loss in patients treated with pulses of methylprednisolone is not negligible: a short term prospective observational study. Ann Rheum Dis 2004; 63 (8) 940-944
82 Assouline-Dayan Y, Chang C, Greenspan A, Shoenfeld Y, Gershwin ME. Pathogenesis and natural history of osteonecrosis. Semin Arthritis Rheum 2002; 32 (2) 94-124
83 Taylor LJ. Multifocal avascular necrosis after short-term high-dose steroid therapy. A report of three cases. J Bone Joint Surg Br 1984; 66 (3) 431-433
84 Good AE. Bilateral aseptic necrosis of femur following a 16-day course of corticotropin. JAMA 1974; 228 (4) 497
85 Mankin HJ. Nontraumatic necrosis of bone (osteonecrosis). N Engl J Med 1992; 326 (22) 1473-1479
86 Pecora PG, Kaplan B. Corticosteroids and ulcers: is there an association?. Ann Pharmacother 1996; 30 (7-8) 870-872
87 Hernández-Díaz S, Rodríguez LA. Steroids and risk of upper gastrointestinal complications. Am J Epidemiol 2001; 153 (11) 1089-1093
88 Duru N, van der Goes MC, Jacobs JW , et al. EULAR evidence-based and consensus-based recommendations on the management of medium to high-dose glucocorticoid therapy in rheumatic diseases. Ann Rheum Dis 2013; 72 (12) 1905-1913
89 Mohan N, Edwards ET, Cupps TR , et al. Demyelination occurring during anti-tumor necrosis factor alpha therapy for inflammatory arthritides. Arthritis Rheum 2001; 44 (12) 2862-2869
90 Radis CD, Kahl LE, Baker GL , et al. Effects of cyclophosphamide on the development of malignancy and on long-term survival of patients with rheumatoid arthritis. A 20-year followup study. Arthritis Rheum 1995; 38 (8) 1120-1127
91 Bernatsky S, Clarke AE, Suissa S. Hematologic malignant neoplasms after drug exposure in rheumatoid arthritis. Arch Intern Med 2008; 168 (4) 378-381
92 Talar-Williams C, Hijazi YM, Walther MM , et al. Cyclophosphamide-induced cystitis and bladder cancer in patients with Wegener granulomatosis. Ann Intern Med 1996; 124 (5) 477-484
93 Faurschou M, Sorensen IJ, Mellemkjaer L , et al. Malignancies in Wegener's granulomatosis: incidence and relation to cyclophosphamide therapy in a cohort of 293 patients. J Rheumatol 2008; 35 (1) 100-105
94 Monach PA, Arnold LM, Merkel PA. Incidence and prevention of bladder toxicity from cyclophosphamide in the treatment of rheumatic diseases: a data-driven review. Arthritis Rheum 2010; 62 (1) 9-21
95 Knight A, Askling J, Granath F, Sparen P, Ekbom A. Urinary bladder cancer in Wegener's granulomatosis: risks and relation to cyclophosphamide. Ann Rheum Dis 2004; 63 (10) 1307-1311
96 Grossfeld GD, Litwin MS, Wolf Jr JS , et al. Evaluation of asymptomatic microscopic hematuria in adults: the American Urological Association best practice policy—part II: patient evaluation, cytology, voided markers, imaging, cystoscopy, nephrology evaluation, and follow-up. Urology 2001; 57 (4) 604-610
97 Hofland CA, Mariani AJ. Is cytology required for a hematuria evaluation?. J Urol 2004; 171 (1) 324-326
98 Ramiro S, Gaujoux-Viala C, Nam JL , et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis 2014; 73 (3) 529-535
99 Penn I. Cancers complicating organ transplantation. N Engl J Med 1990; 323 (25) 1767-1769
100 Fallah M, Liu X, Ji J, Försti A, Sundquist K, Hemminki K. Hodgkin lymphoma after autoimmune diseases by age at diagnosis and histological subtype. Ann Oncol 2014; 25 (7) 1397-1404
101 Dias C, Isenberg DA. Susceptibility of patients with rheumatic diseases to B-cell non-Hodgkin lymphoma. Nat Rev Rheumatol 2011; 7 (6) 360-368
102 Raptopoulou A, Sidiropoulos P, Boumpas D. Ovarian failure and strategies for fertility preservation in patients with systemic lupus erythematosus. Lupus 2004; 13 (12) 887-890
103 Blumenfeld Z, Mischari O, Schultz N, Boulman N, Balbir-Gurman A. Gonadotropin releasing hormone agonists may minimize cyclophosphamide associated gonadotoxicity in SLE and autoimmune diseases. Semin Arthritis Rheum 2011; 41 (3) 346-352
104 Masala A, Faedda R, Alagna S , et al. Use of testosterone to prevent cyclophosphamide-induced azoospermia. Ann Intern Med 1997; 126 (4) 292-295
105 Somers EC, Marder W, Christman GM, Ognenovski V, McCune WJ. Use of a gonadotropin-releasing hormone analog for protection against premature ovarian failure during cyclophosphamide therapy in women with severe lupus. Arthritis Rheum 2005; 52 (9) 2761-2767
106 Henes M, Henes JC, Neunhoeffer E , et al. Fertility preservation methods in young women with systemic lupus erythematosus prior to cytotoxic therapy: experiences from the FertiPROTEKT network. Lupus 2012; 21 (9) 953-958
107 Elizur SE, Chian RC, Pineau CA , et al. Fertility preservation treatment for young women with autoimmune diseases facing treatment with gonadotoxic agents. Rheumatology (Oxford) 2008; 47 (10) 1506-1509
108 Jones TS, Yang W, Evans WE, Relling MV. Using HapMap tools in pharmacogenomic discovery: the thiopurine methyltransferase polymorphism. Clin Pharmacol Ther 2007; 81 (5) 729-734
109 Wolach O, Bairey O, Lahav M. Late-onset neutropenia after rituximab treatment: case series and comprehensive review of the literature. Medicine (Baltimore) 2010; 89 (5) 308-318
110 Katsifis GE, Tzioufas AG, Vlachoyiannopoulos PG, Voulgarelis M, Moutsopoulos HM, Ioannidis JP. Risk of myelotoxicity with intravenous cyclophosphamide in patients with systemic lupus erythematosus. Rheumatology (Oxford) 2002; 41 (7) 780-786
111 American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 Update. Arthritis Rheum 2002; 46 (2) 328-346
112 Anelli MG, Scioscia C, Grattagliano I, Lapadula G. Old and new antirheumatic drugs and the risk of hepatotoxicity. Ther Drug Monit 2012; 34 (6) 622-628
113 Alarcón GS, Kremer JM, Macaluso M , et al; Methotrexate-Lung Study Group. Risk factors for methotrexate-induced lung injury in patients with rheumatoid arthritis. A multicenter, case-control study. Ann Intern Med 1997; 127 (5) 356-364
114 Roubille C, Haraoui B. Interstitial lung diseases induced or exacerbated by DMARDS and biologic agents in rheumatoid arthritis: a systematic literature review. Semin Arthritis Rheum 2014; 43 (5) 613-626
115 Caress JB, Hobson-Webb L, Passmore LV, Finkbiner AP, Cartwright MS. Case-control study of thromboembolic events associated with IV immunoglobulin. J Neurol 2009; 256 (3) 339-342
116 Orbach H, Katz U, Sherer Y, Shoenfeld Y. Intravenous immunoglobulin: adverse effects and safe administration. Clin Rev Allergy Immunol 2005; 29 (3) 173-184
117 Carbone J. Adverse reactions and pathogen safety of intravenous immunoglobulin. Curr Drug Saf 2007; 2 (1) 9-18