Interferon with multiple sclerosis

Fifth, when total refusal is advised, political will is sometimes tested. The best example from the United Kingdom concerns beta interferon for multiple sclerosis NICE twice advised against its use on grounds of lack of cost effectiveness. Faced with a potential political backlash, the ministry devised a risk-sharing plan under which patients were to be monitored over time. If the long-term outcome for patients is not as good as the manufacturers suggest, they may have to refund some of their sales revenues (U.K. Department of Health 2002). 

Pharmacokinetics The pharmacokinetics of interferon beta-la (Rebif) in patients with multiple sclerosis have not been evaluated. In healthy subjects, a single injection resulted in a peak serum concentration at about 16 hours after administration. The mean serum elimination half-life was 69 hours but varied widely. Following every-other-day subcutaneous injections, an increase in the area under the serum concentration versus time curve (AUC) of approximately 240% was observed. Clearance has been estimated at 33 to 55 liters/h. 

Among 700 patients with multiple sclerosis treated with interferon beta-la (n = 467) or beta-lb (n = 233), overt hyperthyroidism occurred in five patients treated with interferon-beta-lb, three of whom required withdrawal and long-term carbimazole, while there were two cases of hypothyroidism and one of goiter without thyroid... 

In 106 patients (76 women) with multiple sclerosis who received interferon beta-la or beta-lb for up to 84 (median 42) months, there was baseline thyroid autoimmunity in 8.5% and hypothyroidism in 2.8% (562). Thyroid dysfunction (80% hypothyroidism, 92% subclinical, 56% transient) developed in 24% (68% with autoimmunity) and autoimmunity in 23% (46% with dysfunction), without a significant difference between the two cytokines 68% of the cases of dysfunction occurred within the first year. Thyroid dysfunction was generally subclinical and was transient in over half of cases. Autoimmunity was the only predictive factor for the development of dysfunction (relative risk = 8.9), but sustained disease was also significantly associated with male sex. 

Schwid SR, Goodman AD, Mattson DH. Autoimmune hyperthyroidism in patients with multiple sclerosis treated with interferon beta-lb. Arch Neurol 1997 54(9) 1169-90. 

McDonald ND, Pender MP. Autoimmune hypothyroidism associated with interferon beta-lb treatment in two patients with multiple sclerosis. Aust NZ J Med 2000 30(2) 278-9. 

Deisenhammer F, Schellekens H, Bertolotto A. Measurement of neutralizing antibodies to interferon beta in patients with multiple sclerosis. J Neurol. 2004 251(suppl 2) II31—1139. 

Patten SB, Francis G, Metz LM, Lopez-Bresnahan M, Chang P, Curtin F. The relationship between depression and interferon beta-la therapy in patients with multiple sclerosis. Mult Scler 2005 11 175-81. 

Your brother had some double vision problems lately and has felt very rired. Your family physician sent him to a neurologist w ho scheduled several tests. On follow up, the neurologist says that your brother has optic neuritis that may potentially be associated with multiple sclerosis. The neurologist also recommends that your brother consider beginning an interferon 3 therapy. 

Volhner TL, Philips JT, Goodman AD, Agius MA, Libonati MA, Giacchino JL, Grundy JS (2004) An open-label safety and drug interaction study of natalizumab (Antegren) in combination with interferon-beta (Avonex) in patients with multiple sclerosis. Multi Scler Oct 10(5) 511-520. 

An anaphylactoid reaction (angioedema, generalized urticaria, worsening bronchospasm, and marked hypotension) occurred in a 35-year-old man with multiple sclerosis who became allergic to methylprednisolone (dose not stated) after starting treatment with interferon beta-lb (258). He had previously been treated with different courses of methylprednisolone. Clinicians should be aware that the complexity of the effects of interferon beta-lb on the immune system can lead to unexpected outcomes. It is uncertain whether the sequence of events here was due to an effect of interferon beta-lb or to coincidence. 

While no evidence of thjroid dysfunction or antithjroid antibodies was found in 20 patients receiving interferon beta during 24 weeks for hematological mahgnancies (31), antithyroid antibodies were detected in 29% of patients with multiple sclerosis after a prospective follow-up performed at 6, 12, and 18 months of treatment (32). Biological thyroid abnormalities without antithyroid antibodies have also been found (SEDA-20, 332). Overall, thyroid disorders with antithyroid antibodies were reported in only three patients on long-term interferon beta treatment for multiple sclerosis (32,33). 

Nephrotic syndrome with segmental glomerulosclerosis has been reported in a 32-year-old woman with multiple sclerosis receiving interferon beta (46). 

Intravascular papillary endothelial hyperplasia with multiple lesions on both hands has been attributed to interferon beta-lb in a 50-year-old man with multiple sclerosis (57). 

Data on outcomes in pregnancy after treatment with interferon beta-la in patients with multiple sclerosis have been obtained from clinical trials (78). Of 29 pregnancies that occurred during or shortly after treatment withdrawal, 13 resulted in normal outcomes, two in premature births, one in fetal death, six in induced abortions, and seven in spontaneous abortions. 

Gotsman I, Elhallel-Darnitski M, Friedlander Z, Haviv YS. Beta-interferon-induced nephrotic syndrome in a patient with multiple sclerosis. Chn Nephrol 2000 54(5) 425-6. 

Webster GF, Knobler RL, Lublin FD, Kramer EM, Hochman LR. Cutaneous ulcerations and pustular psoriasis flare caused by recombinant interferon beta injections in patients with multiple sclerosis. J Am Acad Dermatol 1996 34(2 Pt 2) 365-7. 

Sanberg-Wollheim M. Outcome of pregnancy during treatment with interferon-beta-la (Rebif) in patients with multiple sclerosis. Neurology 2002 58(Suppl) A445-6. 

Recombinant (3-interferon is the first drug known to decrease the frequency and severity of episodes resulting from the effects of demyelination in patients with multiple sclerosis. 

The biotechnology industry had its share of major R D and clinical trial success. The big gains for biotech products are mainly in anemia cancer TNF alpha inhibitors human insulin with short, mixed, and long duration of action interferon for multiple sclerosis and hepatitis C monoclonal antibodies for cancer RSV and immuno-inflammatory diseases. This success has resulted in attracting top pharmaceutical companies and R D funds for biosimilar products with improved properties. It is easier for start-up companies in the above areas to attract capital and angel investors or to conclude licensing deals and find marketing partners. 

Bertolotto A, Malucchi S, Sala A, et al. (2002). Differential effects of three interferon betas on neutralising antibodies in patients with multiple sclerosis a follow up study in an independent laboratory. J. Neurol. Neurosurg. Psychiatry 73 148-153. 

The client with multiple sclerosis is being treated with the biologic response modifier interferon beta-la (Avonex). Which diagnostic test would the nurse monitor to determine the effectiveness of the medication ... 

Acute hepatitis was reported in a 24-year-old woman with multiple sclerosis who had been consuming noni juice (dose and frequency not specified) for 4 weeks. The woman had been treated with interferon bla (IFN) for 6 weeks, a drug that commonly causes hepatic dysfunction of varying severity in multiple sclerosis patients (Francis et al. 2003). IFN was initially suspected as the cause of hepatotoxicity in this case. IFN administration was ceased, and approximately 1 week later noni was ceased. Liver enzyme levels (ALT and bilirubin) increased dramatically for 2 weeks after cessation of IFN and then returned to normal levels (Yuce et al. 2006). 

Gavasso S, Gjtatsen B, Anderssen E, Myhr K, Vedeler C. Immunogenic effects of recombinant interferon-beta therapy dismpt the JAK/STAT pathway in primary immune cells from patients with multiple sclerosis. Mult Scler. 2012 18 1116-24. 

Systemic sclerosis developed in a 38-year-old woman with multiple sclerosis after treatment with interferon beta [63 ]. 

Infection risk A 43-year-old woman with multiple sclerosis treated with subcutaneous interferon beta developed right lower abdominal quadrant pain, fever, and an indurated McBumey point [64 ]. An... 

Immunologic Two patients developed systemic immune responses 1-2 months after withdrawal of interferon beta, characterized by mouth ulcers, a photosensitivity rash, and transient formation of autoantibodies that required glucocorticoid therapy for resolution in an open baseline versus treatment phase II clinical trial of daclizumab in patients with multiple sclerosis and an inadequate response to interferon beta [211 ]. In rare cases severe hypersensitivity reactions after daclizumab have been reported. 

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