From +alt.support.mult-sclerosis Mon Jul 31 20:45:16 1995 From: lbarnett@ix.netcom.com (Laura Barnett ) Date: 29 Jul 1995 16:14:23 GMT Newsgroups: alt.support.mult-sclerosis Subject: Abstracts on Betaseron Dear Friends, Here are some current research findings on Betaseron taken off Medline. Maybe some useful information to glean. Laura Barnett To: lbarnett@ix.netcom.com ~From: "Melvyl System" ~Subject: (id: MSC26162) MELVYL system mail result ~Date: Thu, 27 Jul 95 20:54:38 PDT Search request: F SET 1 AND 2 Search result: 31 citations in the Medline database Display: ABS 1. van Oosten BW; Truyen L; Barkhof F; Polman CH. Multiple sclerosis therapy. A practical guide. Drugs, 1995 Feb, 49(2):200-12. (UI: 95246624) Pub type: Journal Article; Review; Review, Tutorial. Abstract: A growing amount of evidence suggests that a disturbance of immunological function is of importance in the pathogenesis of multiple sclerosis. This is reflected in the drugs used to slow progression and to treat relapses. Immunosuppressive drugs such as azathioprine, cyclophosphamide and cyclosporin might have some potential to slow down progression of multiple sclerosis, but their use is limited by potentially serious adverse effects. Recently, it was shown that interferon-beta-1b can diminish the exacerbation rate in multiple sclerosis without leading to unacceptable adverse effects. Nevertheless, symptomatic treatment remains of crucial importance in the management of multiple sclerosis patients. Spasticity, depression, fatigue and urinary, paroxysmal and sensory symptoms can all be alleviated to some extent with pharmacological interventions, although rehabilitation procedures and psychosocial consultations are no less important. Further therapeutic approaches to multiple sclerosis will be directed at either the specificity of the immune response or the grade of activation of the immune response. Magnetic resonance imaging techniques will play an important role in the evaluation of efficacy of new therapeutic agents. 2. Morrison W. Trials and tribulations: patients' perspectives of the Betaseron study. Axone, 1994 Dec, 16(2):51-5. (UI: 95244348) Abstract: The University of British Columbia Multiple Sclerosis (MS) Clinic was one of 11 North American sites involved in the double-blind, placebo-controlled phase III trial of Betaseron in relapsing-remitting MS. UBC participants as a unique sub-study site which required a rigorous evaluation every six weeks for the first two years. Each visit included extensive blood studies, neurological and physical exams by separate physicians. Magnetic Resonance Imaging (MRI) and evaluation by a research nurse. In addition, participants learned to administer the study medication subcutaneously every second day and keep extensive diaries of possible side effects, concomitant medications, neurological signs and symptoms, and incidental environmental events. The attrition rate was low (8%) despite the gruelling requirements of the study. As patients completed their course of therapy (and before unblinding took place) they were asked to complete a simple questionnaire about various aspects of the study. Questions explored their reasons for participation, helpfulness of preparatory information, positive and negative aspects during the trial, and their "guess" at what they were receiving. This paper will summarize the results of the questionnaires and offer suggestions for consideration when organizing long-term outpatient clinical trials. 3. Wilson BA. Interferon beta for treatment of multiple sclerosis. Medsurg Nursing, 1995 Apr, 4(2):151-3. (UI: 95227267) 4. Rudge P. Interferon beta-1b [letter]. Lancet, 1994 Nov 26, 344(8935):1511. (UI: 95057747) Pub type: Letter. 5. Goodkin DE. Role of steroids and immunosuppression and effects of interferon beta-1b in multiple sclerosis. Western Journal of Medicine, 1994 Sep, 161(3):292-8. (UI: 95066033) Pub type: Journal Article; Review; Review, Tutorial. Abstract: Corticosteroids, corticotropin, azathioprine, cyclophosphamide, and IFN-beta 1b have each had a substantial effect on the care of patients with multiple sclerosis and the design of subsequent clinical trials of experimental therapeutics for MS. The use of MRI scanning and more sensitive clinical outcome measures will possibly enable us to complete clinical trials in a fraction of the time required for earlier trials. The release of Betaseron, which favorably alters the attack rate in ambulatory patients with relapsing-remitting MS has brought a sense of renewed optimism to patients with MS, their families, and their care providers. New promising therapies for chronic progressive MS and biologic products possibly capable of enhancing the effects of IFN-beta 1b in patients with relapsing MS are setting the stage for additional important therapeutic advances in this disease. 6. Practice advisory on selection of patients with multiple sclerosis for treatment with Betaseron. Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 1994 Aug, 44(8):1537-40. (UI: 94336038) Pub type: Guideline; Journal Article; Practice Guideline. 7. McDonald WI; Miller DH; Thompson AJ. Are magnetic resonance findings predictive of clinical outcome in therapeutic trials in multiple sclerosis? The dilemma of interferon-beta. Annals of Neurology, 1994 Jul, 36(1):14-8. (UI: 94296060) Pub type: Journal Article; Review; Review, Tutorial. 8. Jacobs L; Goodkin DE; Rudick RA; Herndon R. Advances in specific therapy for multiple sclerosis. Current Opinion in Neurology, 1994 Jun, 7(3):250-4. (UI: 94362924) Pub type: Journal Article; Review; Review, Tutorial. Abstract: During the past year, two new agents have been demonstrated to be of value in multiple sclerosis. The first agent, a form of recombinant interferon beta (Betaseron; Berlex Labs, Cedar Knolls, NJ), is effective in reducing relapses and also prevent accumulation of brain lesions over time, but has no demonstrated effect on the accumulation of disability over time. The second agent, methylprednisolone (Solumedrol; The Upjohn Co., Kalamozoo, MI), administered in megadose pulses over several days and followed by an oral prednisone taper, reduces the conversion rate of patients with optic neuritis to multiple sclerosis by approximately 50% over 2 years compared with placebo or oral prednisone alone. The mechanisms by which these agents exert their benefits are incompletely understood, but both have complex, relatively widespread effects on the immune systems. The demonstration of efficacy for both of these agents represent landmarks in the search for an effective treatment for multiple sclerosis; both agents seem to provide prophylaxis against future relapses, and methylprednisolone seems to delay the development of the disease. Their introduction into the clinical environment will undoubtedly have a profound effect on the day-to-day care of multiple sclerosis patients as well as the designs of future basic and clinical research. Other new therapies that have substantial potential for benefit in multiple sclerosis but require further definitive study include intramuscular copolymer 1 for relapsing disease and low-dose oral methotrexate and booster doses of intravenous cyclophosphamide for chronic progressive disease. 9. Connelly JF. Interferon beta for multiple sclerosis. Annals of Pharmacotherapy, 1994 May, 28(5):610-6. (UI: 94348160) Pub type: Journal Article; Review; Review, Tutorial. Abstract: OBJECTIVE: To introduce readers to the use of a new agent, interferon beta-1b (IFN beta ser), in the treatment of relapsing-remitting multiple sclerosis (RRMS). Therapeutic and economic issues surrounding IFN beta ser are discussed, as are its pharmacology, clinical efficacy, adverse effects, and dosage guidelines. DATA SOURCES: A MEDLINE search was used to identify pertinent literature, including clinical trials and reviews. STUDY SELECTIONS: All available trials were reviewed. DATA EXTRACTION: Since trials evaluating subcutaneously administered interferon beta are sparse, clinical trials evaluating intrathecal IFN beta ser were included, as was toxicology information from the oncology population. DATA SYNTHESIS: IFN beta ser has recently been approved by the Food and Drug Administration for the treatment of RRMS. Its exact mechanism of action is unknown, but it may downregulate interferon gamma (IFN gamma) production and the IFN gamma-stimulated major histocompatibility complex antigen expression, and/or augment T-suppressor cell function. Primary adverse effects include flu-like symptoms, fever, chills, myalgia, sweating, and injection-site reactions. Clinical efficacy has been investigated in 372 ambulatory patients with RRMS. IFN beta ser treatment resulted in a reduction in the annual exacerbation rate and a greater proportion of exacerbation-free patients. Burden of central nervous system disease was also significantly reduced in treated patients. However, no reductions were detected on the Scripps Neurologic Rating Scale or with confirmed endpoint scores on the Kurtzke Expanded Disability Status Scale. Although many questions remain concerning IFN beta ser's long-term efficacy, its benefits in patients with other types of multiple sclerosis (MS), and its effect on progression of disease and ultimate disability, IFN beta ser is the first treatment modality that has substantially altered the natural course of MS in a controlled clinical trial. CONCLUSIONS: IFN beta ser is not a cure for MS, but it is well tolerated and patients with RRMS have shown significant improvements in exacerbation rates and burden of central nervous system disease. IFN beta ser should be considered a definite improvement in RRMS treatment, although many therapeutic issues remain unanswered. Additional clinical trials are needed. 10. Rudick RA. Betaseron for multiple sclerosis. Implications for therapeutics [editorial]. Archives of Neurology, 1994 Feb, 51(2):125-8. (UI: 94137133) Pub type: Editorial. 11. Kelley CL; Smeltzer SC. Betaseron: the new MS treatment. Journal of Neuroscience Nursing, 1994 Feb, 26(1):52-6. (UI: 94253639) Pub type: Clinical Trial; Journal Article; Multicenter Study; Randomized Controlled Trial; Review; Review, Tutorial. Abstract: Betaseron is a new medication that decreases the frequency and severity of exacerbations in persons with relapsing-remitting MS. It is the first to alter the disease itself and has, therefore, generated considerable hope among patients, families and health care providers. Patients who meet the criteria for use of Betaseron will be confronted with a number of decisions and cost factors. Further, they must be willing to prepare and administer Betaseron injections. Potential adverse effects, direct and indirect costs of Betaseron, and administration and monitoring requirements determine the nursing implications. To provide optimum care and education to patients with MS, nurses must maintain current knowledge about this new medication. 12. Allen A. The high-stakes drug drawing. Journal of Post Anesthesia Nursing, 1994 Feb, 9(1):52-4. (UI: 94157818) Abstract: Betaseron (interferon beta-1b; Chiron, Emeryville, CA) is a promising new drug, the first and only one available for treatment of relapsing-remitting multiple sclerosis (MS). It has been estimated that 350,000 Americans have MS, a neurological disease that affects twice as many women as men. This article reviews the role of the Federal Drug Administration (FDA) and describes steps that take a drug from an idea to a market reality. The random selection process by which initial recipients of limited supplies of Betaseron were chosen is discussed. Financial plans to assist patients with the high cost of the drug and reported adverse effects of the life-long therapy are also included. 13. Piascik P. Administering Betaseron for MS. American Pharmacy, 1994 Jan, NS34(1):21-2. (UI: 94219350) 14. Hughes RA. Immunotherapy for multiple sclerosis [editorial]. Journal of Neurology, Neurosurgery and Psychiatry, 1994 Jan, 57(1):3-6. (UI: 94132822) Pub type: Editorial; Review; Review, Tutorial. 15. Goodkin DE; Kanoti GA. Ethical considerations raised by the approval of interferon beta-1b for the treatment of multiple sclerosis. Neurology, 1994 Jan, 44(1):166-70. (UI: 94119372) 16. Broderick JP; Samaha FJ. Interferon beta treatment of multiple sclerosis [letter]. Neurology, 1994 Jan, 44(1):186; discussion 188-90. (UI: 94119382) Pub type: Letter. 17. Deming QB. Interferon beta treatment of multiple sclerosis [letter]. Neurology, 1994 Jan, 44(1):186; discussion 188-90. (UI: 94119383) Pub type: Letter. 18. Lubic LG. Interferon beta treatment of multiple sclerosis [letter]. Neurology, 1994 Jan, 44(1):186; discussion 188-90. (UI: 94119384) Pub type: Letter. 19. Markovitz DI. Interferon beta treatment of multiple sclerosis [letter]. Neurology, 1994 Jan, 44(1):186; discussion 188-90. (UI: 94119385) Pub type: Letter. 20. McDonald MA; McDonald CM. Interferon beta treatment of multiple sclerosis [letter]. Neurology, 1994 Jan, 44(1):187. (UI: 94119386) Pub type: Letter. 21. Longstreth WT Jr; Franklin GM. Interferon beta treatment of multiple sclerosis [letter]. Neurology, 1994 Jan, 44(1):187; discussion 188-90. (UI: 94119387) Pub type: Letter. 22. Metz L; Bell R; Zochodne D. Interferon beta treatment of multiple sclerosis [letter]. Neurology, 1994 Jan, 44(1):187-8; discussion 188-90. (UI: 94119388) Pub type: Letter. 23. Klapper JA. Interferon beta treatment of multiple sclerosis [letter]. Neurology, 1994 Jan, 44(1):188; discussion 188-90. (UI: 94119389) Pub type: Letter. 24. Pachner AR. Interferon beta treatment of multiple sclerosis [letter]. Neurology, 1994 Jan, 44(1):188; discussion 188-90. (UI: 94119390) Pub type: Letter. 25. Holdcroft C. Interferon-beta 1b: new hope for multiple sclerosis [news]. Nurse Practitioner, 1994 Jan, 19(1):6. (UI: 94188006) Pub type: News. 26. Paty DW; Li DK; Oger JJ; Kastrukoff L; Koopmans R; Tanton E; Zhao GJ. Magnetic resonance imaging in the evaluation of clinical trials in multiple sclerosis. Annals of Neurology, 1994, 36 Suppl:S95-6. (UI: 94288581) Abstract: Magnetic resonance imaging (MRI) provides an objective method of evaluating multiple sclerosis clinical trials and is at least five times more sensitive to disease activity. In a recent clinical trial, MRI was also approximately twice as sensitive as clinical measurements to the treatment effect of a drug. 27. Piascik P. A new treatment for multiple sclerosis. American Pharmacy, 1993 Dec, NS33(12):25-6. (UI: 94136405) 28. Nightingale SL. From the Food and Drug Administration. Jama, 1993 Oct 13, 270(14):1672. (UI: 94017005) 29. Knobler RL; Greenstein JI; Johnson KP; Lublin FD; Panitch HS; Conway K; Grant-Gorsen SV; Muldoon J; Marcus SG; Wallenberg JC; et al. Systemic recombinant human interferon-beta treatment of relapsing-remitting multiple sclerosis: pilot study analysis and six-year follow-up. Journal of Interferon Research, 1993 Oct, 13(5):333-40. (UI: 94132656) Pub type: Clinical Trial; Journal Article; Randomized Controlled Trial. Abstract: A pilot study was undertaken to test the safety and establish the side effect profile of recombinant human interferon-beta 1b (Betaseron, Berlex Laboratories, Richmond, CA), in patients with relapsing-remitting multiple sclerosis (RRMS). During the initial dose finding period (24 weeks), five groups of 6 patients each were treated by subcutaneous injection three times each week with either 0.8, 4, 8, or 16 million units (mU) of Betaseron or placebo (WHO Standard). Although some side effects were noted in all groups, a dose-related trend in reduction of exacerbation frequency and side-effect profile was noted. Patients given 16 mU had no exacerbations during the initial dosing period, but associated side effects led to dose reduction or dropout. An 8 mU dose was selected for further study after 24 weeks, and continuous dosing at 8 mU in 15 patients has now exceeded 6 years. Side effects abated over time. Neutralizing antibody developed in most patients, but titers were variable, fluctuated independently of clinical course, and tended to fall with prolonged treatment. A dose-dependent rise in neopterin levels was observed during the initial dosing period. This pilot study has demonstrated responsiveness to Betaseron, shown a stable safety profile over time, and established guidelines for a dosing regimen to evaluate and optimize further the efficacy of Betaseron in RRMS. 30. Interferon beta-1B for multiple sclerosis. Medical Letter on Drugs and Therapeutics, 1993 Jul 9, 35(900):61-2. (UI: 93295305) 31. Freedman MS; Muth KL; Trotter JL; Yoshizawa CN; Antel JP. Prospective serial analysis of interleukin-2 and soluble interleukin-2 receptor in relapsing-remitting multiple sclerosis [see comments]. Neurology, 1992 Aug, 42(8):1596-601. (UI: 92350462) Abstract: We performed a longitudinal analysis of serum interleukin-2 (IL-2) and soluble IL-2 (sIL-2R) concentrations in 60 patients with relapsing-remitting (R-R) multiple sclerosis (MS) as well as in 33 age- and sex-matched normal controls. Overall, we found that serum IL-2 levels remained low (less than 10 U/ml) and did not change appreciably over time; however, marked fluctuations in sIL-2R levels were observed in both the patient and control groups. Using patients as their own controls, we calculated an interrelapse (disease stable) mean sIL-2R concentration as a baseline for comparison with relapse values; sIL-2R levels greater than the 90th percentile of the Student's t distribution of stable values were defined as "peaks." There were a total of 27 sIL-2R peaks, eight (30%) of which correlated with clinical relapses but were potentially predictive of only 18% (8/45) of all the recorded clinical relapses. There was no difference in disease severity (Expanded Disability Status Scale) score between peak-correlated and noncorrelated relapses. Our data suggest that despite reports of elevated levels of IL-2 and sIL-2R in MS, neither may be a useful marker for predicting clinical disease activity in R-R MS.