A systematic review of the effectiveness of adalimumab

More documents

Recommendations

Info

8 Background medication costs, especially in those treated with biological agents such as TNF inhibitors, account for a majority of the direct costs of RA. 57 Some drug intervention studies have shown reduced work absence with aggressive treatment strategies, 58 although only one-third of employed patients cease because of disease and, unsurprisingly, manual workers are much more likely to stop work. 59 Current service provision Most patients with RA are referred to hospital services for assessment, but up to one-quarter of those with early inflammatory arthritis (not necessarily RA) are managed in primary care. Most district general hospitals now have a department of rheumatology with varied support from clinical nurse specialists and other professionals allied to medicine. The majority of patients followed up in a hospital rheumatology department have RA or another type of inflammatory arthritis or connective-tissue disease. A proportion of such patients may also require inpatient treatment, although there are considerable variations in inpatient facilities and hospitalisation rates for RA. The Arthritis and Musculoskeletal Alliance (ARMA) has recently proposed standards of care for patients with inflammatory arthritis. The principal motive for these standards 60 is to improve service provision and delivery and to reduce regional variations in access to services. 61–63 For example, access to TNF inhibitors varies depending on local funding arrangements, such that some districts operate waiting lists for patients to begin treatment despite wide drug availability. A recent survey, commissioned by ARMA and the British Society for Rheumatology (BSR), with support from Schering-Plough, indicated that around one-third of 148 rheumatologists, mainly from England and Wales, were unable to prescribe TNF inhibitors. 64 Principal barriers to prescribing were identified as difficulties with local funding arrangements or problems of infrastructure such as the availability of day-case facilities or nursing support. Variable implementation of guidance on the use of TNF inhibitors was also confirmed by a survey of 196 hospitals and PCTs undertaken by the Audit Commission, which found that ‘the biggest perceived barrier to implementation among NHS bodies, for both clinical guidelines and technology appraisals, was lack of money. We found that 85 per cent of respondents identified that the funds available to implement technology appraisals were insufficient, particularly in relation to high-cost appraisals, such as … etanercept and infliximab for rheumatoid arthritis.’ 60 Access to adalimumab has caused particular difficulties in some areas because this drug has not yet been evaluated by NICE. However, some services have managed to secure additional funding for drugs and junior medical and nursing staff to enable NICE guidance to be implemented. 65 Description of the technology Adalimumab (Humira ® ; Abbott Laboratories) Adalimumab is a recombinant monoclonal antibody, made from human peptide sequences, which binds specifically to TNF and neutralises its biological functions by blocking interactions with the p55 and p75 cell-surface TNF receptors. Treatment is currently recommended for use in people with moderate or severe RA who have not responded to one or more DMARDs, including methotrexate. An application to extend the licence of adalimumab for use in severe, active, progressive RA in adults not previously treated with methotrexate was submitted by Abbott Laboratories in December 2004 66 and approved in June 2005. 67 Concomitant treatment with methotrexate is recommended for optimum efficacy, but adalimumab may be used alone where methotrexate is not tolerated or is contraindicated. Clearance of adalimumab from the body is decreased with age and by concomitant methotrexate administration, whereas adalimumab increases methotrexate clearance. 68 Patients normally self-administer adalimumab by subcutaneous injections, after training, at a standard dose of 40 mg every other week; but the dose may be increased to 40 mg weekly if disease is poorly controlled. 69 Etanercept (Enbrel ® ; Wyeth Laboratories) Etanercept is a combination protein consisting of the extracellular portion of two of the 75-kDa TNF receptors (TNF-R2) for TNF combined with a human Fc portion of human IgG class 1 (IgG 1). Etanercept binds soluble and cell-bound TNF- with high affinity and does this by competing with TNF receptors. Etanercept is administered as a twice-weekly subcutaneous injection of 25 mg or a once-weekly injection of 50 mg. Patients or caregivers normally administer etanercept, after suitable training. No dose changes are necessary for patients with renal or hepatic failure or in elderly subjects. Etanercept may be used in
combination with methotrexate or alone for the treatment of active RA in adults when the response to DMARDs, including methotrexate (unless contraindicated), has been inadequate, and for the treatment of severe, active and progressive RA not previously treated with methotrexate. Etanercept is also licensed for use in juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis and severe psoriasis. Infliximab (Remicade ® ; Schering-Plough) Infliximab is a recombinant chimeric human–murine monoclonal antibody that binds soluble and membrane-bound TNF-. Stable complexes are formed, binding of TNF- is prevented and TNF- already bound to TNF receptors may be dissociated. The TNF- binding region is of mouse origin and comprises 30% of the amino acid sequence of infliximab. The remainder is a human IgG 1 heavy-chain and kappa-chain constant region. Infliximab is licensed for use in RA with methotrexate, although in clinical practice it is used without methotrexate or with other DMARDs if patients are intolerant of methotrexate. 70 The recommended dose of infliximab for RA is 3mgkg –1 body weight given as an intravenous infusion, followed by further infusion, at the same dose, 2 and 6 weeks later. Thereafter, infusions are given at 8-week intervals. An interval between infusions of greater than 16 weeks is not recommended because of an increased risk of hypersensitivity reactions, although infusions after longer gaps have been administered safely. 62,71,72 Freshly reconstituted infliximab is diluted to a volume of 250 ml using 0.9% sodium chloride and the infusion is administered intravenously over at least 2 hours using a low-protein-binding filter. Treated patients should be observed for 1–2 hours post infusion. Recent studies indicate that patients who tolerate infusions well and are established on therapy may receive infusions over 1 hour or less. 73 Infliximab is also licensed for use in severe Crohn’s disease (5 mg kg –1 ), including disease complicated by fistulae, ankylosing spondylitis (5 mg kg –1 ) and psoriatic arthritis (5 mg kg –1 ). Use of higher doses of infliximab in trials has encouraged use of higher doses or a shorter interval between infusions in RA. 74 Special precautions for use of TNF inhibitors TNF inhibitors may cause a variety of adverse effects. 1 Reactivation of Mycobacterium tuberculosis organisms lying dormant in walled granuloma, in © Queen’s Printer and Controller of HMSO 2006. All rights reserved. Health Technology Assessment 2006; Vol. 10: No. 42 individuals previously infected with tuberculosis, is a particular concern. Such ‘latent’ tuberculosis, thought to be highly prevalent in the world’s population, rarely causes disease. TNF- is a key component of host defence against M. tuberculosis, especially in the formation of granulomas. 75 Inhibition of TNF- appears to increase the risk of M. tuberculosis and other agents causing granulomatous diseases, such as Listeria monocytogenes (a bacterium associated with foodborne diseases) and Histoplasma capsulatum (a fungus which, in endemic areas, causes lung disease in people with a compromised immune system). The risk appears to be significantly greater with infliximab (53 patients per 100,000 treated cases) than with etanercept (28 per 100,000). 76 Data for adalimumab are limited, but an increased risk has also been shown. The summary of product characteristics (SPC) for adalimumab and infliximab and guidance including proposed guidance from the BSR, British Thoracic Society and the British Society for Gastroenterology recommend screening patients before treatment. 77 In RA this is currently done by taking a personal and family history of tuberculosis and a pretreatment chest X-ray, but the addition of skin tests using tuberculin has been proposed. Skin testing before the use of TNF inhibitors poses problems in the UK because of the use of bacille Calmette-Guérin (BCG) vaccination for tuberculosis prevention in childhood. In addition, many patients with RA are poorly responsive to tuberculin, perhaps as a result of previous or current immunosuppressive therapy, but also due to the disease. 78 Preventive antituberculous drug treatment in latent tuberculosis is also associated with a risk of druginduced hepatitis, which needs to be considered in deciding about prophylactic therapy. Routine blood monitoring is not necessary for patients taking TNF inhibitors, but may be needed for concomitantly used DMARDs such as methotrexate. TNF inhibitors can induce antinuclear and anti-double-stranded DNA antibodies in the blood of some patients treated with TNF inhibitors. These antibodies are associated with systemic lupus erythematosus (SLE), a potentially serious rheumatic disease. Cases of drug-induced SLE have been reported with TNF inhibitors, but are rare. 79 Choosing between TNF inhibitors and patient preferences Physicians may prefer one TNF inhibitor to another for clinical reasons; for example, etanercept or adalimumab may be preferred to 9
Page 1 and 2: A systematic review of the effectiv
Page 3 and 4: A systematic review of the effectiv
Page 5 and 6: Objectives: This report reviews the
Page 7: Glossary and list of abbreviations
Page 10 and 11: viii Glossary and list of abbreviat
Page 13 and 14: Background Rheumatoid arthritis (RA
Page 15: increased risk of serious infection
Page 19 and 20: Summary RA is a common, chronic, in
Page 21 and 22: (IL-2) and interleukin-6 (IL-6), pr
Page 23: Assessment of response to DMARDs Re
Page 27: disease between clinic appointments
Page 30 and 31: 14 Effectiveness in juvenile arthri
Page 32 and 33: 16 Effectiveness adalimumab plus me
Page 34 and 35: 18 Effectiveness Monoclonal Antibod
Page 36 and 37: 20 TABLE 1 Description of included
Page 38 and 39: 22 TABLE 2 Quality of included RCTs
Page 40 and 41: 24 Effectiveness change in modified
Page 42 and 43: 26 Effectiveness TABLE 4 Meta-analy
Page 44 and 45: 28 Effectiveness Review: Adalimumab
Page 46 and 47: 30 Effectiveness Review: Adalimumab
Page 48 and 49: 32 TABLE 6 Effectiveness Descriptio
Page 50 and 51: 34 TABLE 6 Effectiveness Descriptio
Page 52 and 53: 36 TABLE 7 Effectiveness Quality of
Page 54 and 55: 38 Effectiveness etanercept trials.
Page 56 and 57: 40 Effectiveness TABLE 9 Summary of
Page 58 and 59: 42 Effectiveness Review: Etanercept
Page 70 and 71: 54 Effectiveness TABLE 11 Summary o
Page 72 and 73: 56 TABLE 12 Description of included
Page 74 and 75:
58 TABLE 13 Quality of included RCT
Page 76 and 77:
60 Effectiveness per week and escal
Page 78 and 79:
62 Effectiveness significant advant
Page 80 and 81:
64 Effectiveness Review: Infliximab
Page 82 and 83:
66 Effectiveness Review: Infliximab
Page 84 and 85:
68 Effectiveness FIGURE 44 Malignan
Page 86 and 87:
70 TABLE 17 Effectiveness Summary o
Page 89 and 90:
Summary of review of existing econo
Page 91 and 92:
TABLE 20 Summary of published ICERs
Page 93 and 94:
TABLE 21 Published etanercept econo
Page 95 and 96:
TABLE 23 Published economic analyse
Page 97 and 98:
TABLE 25 Treatment sequences: adali
Page 99 and 100:
management of RA, i.e. 1st and 2nd
Page 101 and 102:
To estimate the long-term consequen
Page 103 and 104:
TABLE 32 TNF inhibitors as last act
Page 105 and 106:
TABLE 34 Basic structure of the mod
Page 107 and 108:
een quit on grounds of toxicity, ad
Page 109 and 110:
TABLE 39 Strategy set: adalimumab a
Page 111 and 112:
TABLE 43 Beta distributions for HAQ
Page 113 and 114:
TABLE 44 Early cessation of DMARDs:
Page 115 and 116:
TABLE 46 Unit costs for tests and v
Page 117 and 118:
following properties, according to
Page 119 and 120:
TABLE 52 Base case: TNF inhibitors
Page 121 and 122:
TABLE 54 Base case: TNF inhibitors
Page 123 and 124:
TABLE 59 Third TNF inhibitor follow
Page 125 and 126:
TABLE 65 Sensitivity analyses: TNF
Page 127 and 128:
TABLE 67 Sensitivity analyses: TNF
Page 129:
The substantial economic impact of
Page 133 and 134:
Summary Effectiveness: principal fi
Page 135 and 136:
inhibitors, although the incrementa
Page 137 and 138:
introduce bias which generally exag
Page 139:
Adalimumab, etanercept and inflixim
Page 143 and 144:
1. Jobanputra P, Barton P, Bryan S,
Page 145 and 146:
46. Young A, Dixey J, Cox N, Davies
Page 147 and 148:
tumor necrosis factor therapy in th
Page 149 and 150:
arthritis: a 12-week, double-blind,
Page 151 and 152:
171. Geborek P, Crnkic M, Petersson
Page 153 and 154:
216. Schotte H, Willeke P, Mickholz
Page 155 and 156:
The Health Assessment Questionnaire
Page 157 and 158:
Cochrane Library (CENTRAL) 2005 Iss
Page 159 and 160:
Appendix 3 © Queen’s Printer and
Page 161:
TABLE 69 Studies excluded from clin
Page 164 and 165:
148 Appendix 4 TABLE 71 Meta-analys
Page 166 and 167:
150 Appendix 4 TABLE 73 Meta-analys
Page 168 and 169:
152 Appendix 4 Infliximab versus pl
Page 170 and 171:
154 Appendix 4 Infliximab plus MTX
Page 173:
Ovid MEDLINE(R) 1966 to February we
Page 177 and 178:
Appendix 8 © Queen’s Printer and
Page 179 and 180:
TABLE 79 Wong et al., 2002 161 © Q
Page 181 and 182:
TABLE 80 Kobelt et al., 2003 162 (c
Page 183 and 184:
TABLE 82 Brennan et al., 2004 160
Page 185 and 186:
Page 187 and 188:
TABLE 85 Bansback et al., 2005 166
Page 189:
Page 192 and 193:
176 Appendix 9 TABLE 89 Strategy se
Page 195 and 196:
Extensive sensitivity analysis was
Page 197 and 198:
TABLE 96 Variation 1: TNF inhibitor
Page 199 and 200:
TABLE 99 Variation 2: TNF inhibitor
Page 201 and 202:
TABLE 102 Variation 3: TNF inhibito
Page 203 and 204:
Page 205 and 206:
Page 207 and 208:
Page 209 and 210:
Page 211 and 212:
Page 213 and 214:
Page 215 and 216:
Page 217 and 218:
Page 219 and 220:
Page 221 and 222:
TABLE 132 Variation 10: TNF inhibit
Page 223 and 224:
Page 225 and 226:
Page 227 and 228:
Page 229 and 230:
Page 231 and 232:
Page 233 and 234:
Page 235 and 236:
Page 237 and 238:
Page 239 and 240:
Page 241 and 242:
Page 243:
Page 247 and 248:
Volume 1, 1997 No. 1 Home parentera
Page 249 and 250:
No. 3 Screening for sickle cell dis
Page 251 and 252:
No. 25 A rapid and systematic revie
Page 253 and 254:
No. 11 First and second trimester a
Page 255 and 256:
No. 23 Clinical effectiveness and c
Page 257 and 258:
No. 28 Outcomes of electrically sti
Page 259:
No. 28 Adefovir dipivoxil and pegyl
Page 262 and 263:
246 Health Technology Assessment Pr
Page 264:
248 Health Technology Assessment Pr
show all

A systematic review of the effectiveness of adalimumab

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?