Results from a pooled analysis of nine efficacy studies of alefacept for the treatment of plaque psoriasis indicated that alefacept has similar efficacy and safety in obese and diabetic 362 patients compared with patients without these comorbidities order 20 mg erectafil fast delivery erectile dysfunction treatment in trivandrum. A post hoc subgroup analysis of a large safety trial determined the safety profile of anakinra in patients with comorbidities (cardiovascular events buy 20mg erectafil with mastercard erectile dysfunction treatment needles, pulmonary events purchase erectafil 20 mg without a prescription erectile dysfunction drugs walgreens, diabetes, Targeted immune modulators 102 of 195 Final Update 3 Report Drug Effectiveness Review Project 363,368 infections, malignancies, renal impairment, and central nervous system-related events). Overall, the incidence rates of adverse events were similar regardless of comorbidity status. In a prospective cohort study of 4167 Swedish rheumatoid arthritis patients taking 290 antitumor necrosis factor drugs (adalimumab, etanercept or infliximab), the risk for hospitalization with any infection was significantly increased for patients with comorbid cardiovascular disease, adjusted relative risk 1. However, this study did not report results by specific antitumor necrosis factor drugs. No direct evidence on the comparative risk of targeted immune modulators in patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, or plaque psoriasis and congestive heart failure exists. The existing evidence on the risk of cardiovascular events and congestive heart failure with antitumor necrosis factor therapy is mixed. A large retrospective cohort study (N=13 171) based on the National Databank for Rheumatic Diseases reported an absolute risk reduction for congestive heart failure of 1. A retrospective cohort study based on the British Society for Rheumatology Biologics Register found that the risk for myocardial infarction is substantially reduced in patients responding to antitumor necrosis factor therapy after 6 months compared with nonresponders 334 (3. By contrast, indirect evidence indicates an increased risk of worsening heart failure and 369 mortality during antitumor necrosis factor alpha therapy. One trial evaluated efficacy of infliximab for the treatment of congestive heart failure. Infliximab was associated with higher 369 mortality rates in the 10 mg/kg arm than in the placebo and 5 mg/kg arm. This evidence on congestive heart failure is presented in greater detail in Key Question 2. Other subgroups We found a case series of 131 pregnant women exposed to infliximab; however, this study did 370 not meet our eligibility criteria. We describe it briefly because it is the only study addressing pregnant women. This study did not detect an increased risk of adverse pregnancy outcomes compared with the general population. However, the sample size of this study was small and limitations of case series must be kept in mind. In addition, 27% of patients were lost to follow- up. Other commonly prescribed medications No formal drug interaction studies have been performed with any targeted immune modulators. Concurrent administration of anakinra with tumor necrosis factor-blocking agents (i. This evidence came from a 24-week trial comparing concurrent treatment with 50 anakinra and etanercept to etanercept monotherapy in patients with rheumatoid arthritis. Patients treated with both anakinra and etanercept had a 7% rate of serious infections compared with no infections observed in patients treated with etanercept alone. Two percent of patients treated concurrently with anakinra and etanercept developed neutropenia. Because adalimumab and infliximab have a similar mechanism of action to etanercept, similar risks are believed to be associated with concurrent treatment with anakinra, although no formal evidence exists. Targeted immune modulators 103 of 195 Final Update 3 Report Drug Effectiveness Review Project Because the majority of patients included in clinical studies received one or more concomitant medications (e. One analysis of data from the first 6 months of a large, blinded, placebo-controlled safety trial of anakinra provides evidence for the risk of infections or 371 other serious adverse events for some concomitant medications. In this trial, no statistically significant differences were noted in the risk of infection or other serious adverse events between placebo- and anakinra-treated patients concurrently taking methotrexate or other disease- modifying antirheumatic drugs. Two patients taking anakinra and azathioprine developed serious infections compared with no patients taking azathioprine and placebo, although the number of patients taking azathioprine was deemed to be too small to draw any definitive conclusions. The adverse event profiles were similar for anakinra and placebo for patients who were or were not taking concomitant antihypertensive, antidiabetic, or statin drugs. Concomitant administration of adalimumab and methotrexate has demonstrated a 29% to 44% reduction in the clearance of adalimumab. However, data do not suggest the need for dose 372 adjustment of either methotrexate or adalimumab. Studies evaluating concomitant administration of methotrexate with anakinra or etanercept have not demonstrated changes in the clearance either drug. Although no formal studies have evaluated drug interactions between methotrexate and alefacept, or infliximab, concomitant administration of these agents is believed to be safe. Targeted immune modulators 104 of 195 Final Update 3 Report Drug Effectiveness Review Project Table 20. Summary of studies assessing subgroups Quality Author, year Study design N Duration Drug Population Results Rating Age Fleischmann Pooled safety Patients with RA, No differences in adverse events between 360 4322 NR Anti-TNF Fair et al. Pooled analysis Patients with 362 NR 12 weeks Alefacept between patients older and younger than 65 Fair 2005 of efficacy trials plaque psoriasis years Significantly higher risk factor for bacterial Takeuchi et Postmarketing 350 5000 6 months Infliximab Patients with RA pneumonia in patients older than 70 vs. Prospective 3694 Etanercept Patients younger than 65 years had better 42 52 weeks Patients with RA Fair 2006 cohort study Infliximab response Race Significantly higher response rates in Japanese Asahina 2010 Patients with 238 RCT 169 24 weeks Adalimumab patients treated with drug compared with Fair plaque psoriasis placebo No significant difference in ACR 20 response Chen, 2009 RCT 47 12 Adalimumab Patients with RA rates in Taiwanese patients treated with drug Fair 74 compared with placebo Significantly higher response rates with drug Tsai 2011 Patients with 366 RCT 121 36 weeks Ustekinumab compared with placebo in Taiwanese Fair plaque psoriasis and Korean patients 7345 person- Prospective years Adalimumab Dixon 2010 cohort study DMARD, Incidence rate of tuberculosis statistically 271 13739 Etanercept Patients with RA Fair BSRBR 34025 significantly higher in non white patients Infliximab Registry person- years anti- TNF Comorbidities Infliximab-treated (10 mg) patients were more Chung et al. Pooled analysis Patients with 362 NR 12 weeks Alefacept diabetic and obese patients compared with the Fair 2005 of efficacy trials plaque psoriasis general study population 16126 Adalimumab Significantly reduced risk of myocardial infarction Dixon et al. Retrospective 334 10840 person etanercept, Patients with RA in responders to anti-TNF treatment compared Good 2007 cohort study years infliximab with non responders Schiff et al. More SAEs in abatacept-treated patients with 353 NR 52 weeks Patients with RA Fair al. Patients with RA 364 RCT 535 16 weeks incidence of SAEs in patients with diabetes and Fair al. Retrospective Patients on anti-TNF treatment had a lower rate 328 13171 2 years Anti-TNF Patients with RA Fair 2004 cohort study of CHF than patients on traditional RA therapy Concomitant medications Patients treated with both anakinra and Genovese et Anakinra + etanercept had a 7% rate of serious infection, 50 RCT 242 24 weeks Patients with RA Fair al. The adverse event profiles were similar for Tesser et al. Gender Prospective Kristensen 367 observational 1565 3 months Anti-TNF Patients with RA Gender did not influence treatment response Fair 2008 study Takeuchi et Postmarketing Significantly higher risk factor for bacterial 350 5000 6 months Infliximab Patients with RA NA al. Targeted immune modulators 106 of 195 Final Update 3 Report Drug Effectiveness Review Project SUMMARY Our conclusions are based on the review of 5210 abstracts and the inclusion of 163 studies. The large majority of these studies were funded by the pharmaceutical industry and could be classified as efficacy trials with highly selected patients. Few studies existed that enrolled less selected, primary care based populations. Overall, however, results between efficacy trials and more generalizable effectiveness studies appear to be consistent with only small variations in the magnitude of effects (see Table 21). In summary, insufficient evidence exists for most comparisons about the efficacy, effectiveness, and safety of abatacept, adalimumab, alefacept, anakinra, certolizumab pegol, etanercept, golimumab, infliximab, natalizumab, rituximab, tocilizumab, and ustekinumab for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn’s disease, ulcerative colitis, and plaque psoriasis. The most obvious differences that might be clinically decisive for choosing a targeted immune modulator involve dosage and administration. Infliximab, natalizumab, rituximab, and tocilizumab require intravenous administration.
Finally generic erectafil 20 mg without prescription erectile dysfunction medication muse, digital rectal and Ultrasound recto-vaginal examinations should be considered purchase erectafil 20 mg with mastercard erectile dysfunction nerve, The goal of imaging is to make the most accurate especially if the diagnosis is unclear and appendicitis 10 diagnosis using the least amount of radiation purchase erectafil 20mg without a prescription erectile dysfunction pills south africa. Ultrasound, particularly transvaginal ultrasound, re- mains the primary diagnostic instrument of choice. Laboratory investigation Other imaging modalities also may play a key Basic laboratory investigations are helpful in pro- supplemental role where available10,11. See Chapter viding guidance to a possible diagnosis. Generally, 1 on how to perform and evaluate ultrasound. A pregnancy test is a useful only imaging technique available, especially abdo- initial test, performed commonly using urine minal ultrasound, although in some places even this human chorionic gonadotropin (hCG) testing; is not available. Although magnetic resonance im- the urine beta subunit (βhCG) is sensitive to aging (MRI) and computed tomography (CT) 25mIU/ml (25IU/l) depending on the test your scans are a useful adjunct, they are mostly unavail- laboratory uses, and becomes positive 3–4 days able or restricted to a few specialized centers and after implantation. A positive pregnancy test should raise suspicion High-resolution ultrasound provides specific of associated pregnancy complications such as abor- features of acute appendicitis. The inflamed appen- tions, ectopic pregnancies and others. Urine or dix is widened and may be detected (diameter vaginal swab microscopy, culture and sensitivity >6mm). It is useful in doubtful cases especially may be indicated. The presence of red cells, white when gynecological problems are to be excluded10. Ultrasound is useful in evaluating with patient mortality and morbidity12. The equip- patients at risk for ectopic pregnancy, namely by ment needed is very sensitive and expensive. The documenting the presence or absence of an intra- method depends on the availability of carbon dioxide uterine pregnancy. Furthermore, ultrasound can gas although there are some ongoing trials with low- help distinguish a normal intrauterine pregnancy tech equipment including gasless laparoscopy. A firm diagnosis of ectopic where laparoscopy is not available, when the pre- pregnancy, with the gestational sac or fetal pole sumptive diagnosis of acute abdomen, for example positively identified in the adnexal region, is rarely ectopic pregnancy, in an unstable patient necessi- made by sonography alone. However, identifying tates immediate surgery, or when definitive therapy an empty uterus in conjunction with an adnexal is not possible by medical management or laparos- mass that is not of ovarian origin (e. The findings mentioned above for laparos- ‘bagel sign’), and/or pelvic free fluid, is highly pre- copy are the same in laparotomy. Transvaginal ultrasound, although not univers- DIAGNOSIS AND TREATMENT OF ally available in all hospitals, offers a viable alterna- COMMON CAUSES OF ACUTE PELVIC tive to laparoscopy to diagnose and exclude ovarian PAIN endometriomas, but it has no value for peritoneal 6 Pelvic inflammatory disease disease. Sonographic markers for acute and chro- nic PID can be differentiated. Incomplete septation Ascending infection involving the endometrium, of the tubal wall (‘cogwheel sign’) is a marker for fallopian tubes, ovaries and pelvic peritoneum con- acute disease, and a thin wall (‘beaded string’) indi- stitute PID13. Infection could be sexually transmit- cates chronic disease. Thickening is noted in the ted or could be caused by the introduction of pelvic areas during the inflammatory process. It could follow sonography is most valuable in following the deliveries, abortion and major and minor gyneco- progression or regression of an abscess after it has logical surgery13,14. Abdominal X-ray Diagnosis of PID is often clinical, although sen- sitivity and specificity is limited. The positive pre- Air under the diaphragm in the erect position is in 12 dictive value of laparoscopy diagnosis is 65–90%. In intestinal ob- Major features include lower abdominal pain and struction the gut is dilated and fluid levels in the 8,9 tenderness, cervical excitation and adnexal tender- bowel are evident. Other symptoms include deep dyspareunia, abnormal vaginal and cervical dis- Laparoscopy charge, intermenstrual or post-coital bleeding, and Laparoscopy is commonly unavailable in most low- fever >38°C12. Where available, laparoscopy Gynecological examination and imaging may may help to establish a diagnosis, especially in cases reveal uterine tenderness, cervical excitation and of an unruptured ectopic, or if diagnosis is in doubt. Laboratory findings may peritoneal endometriosis where it is superior to show leukocytosis >10,000ml, Gram-negative transvaginal ultrasound. On direct visualization, intracellular diplococci or Chlamydia trachomatis by implants are seen; however the skill and experience rapid diagnostic test in the cervical exudates or pus of the surgeon are important12. Although not commonly 58 Acute Pelvic Pain in Limited-resource Setting available in developing countries, the gold standard resultant massive intraperitoneal bleeding from a for diagnosis remains laparoscopy when pelvic in- ruptured or slow-leaking ectopic in such patients. In some cases intraperitoneal bleed- cases could be false negative12. The antibiotic regimen is variable for treatment This could manifest with ‘toilet signs’ which in- of PID according to national guidelines. Broad- clude urinary frequency, dysuria and tenesmus, and spectrum antibiotics are recommended to cover there are reported cases of patients fainting in the common pathological agents including Neisseria toilet or following sexual intercourse. Local sensitivity patterns of or- low blood pressure, elevated pulse rate and cold ganisms should dictate antibiotics. In low-resource clammy extremities in cases of ruptured ectopic countries irrational drug use, affordability, avail- with significant intraperitoneal bleeding. Findings ability and lack of laboratory support are key chal- on pelvic examination include bleeding, pouch of lenges16. For mild to moderate disease, out-patient Douglas may be bulging, and adnexal masses may treatment is recommended in non-pregnant be felt. There may be cervical excitation tenderness patients. Indications for in-patient management are and bleeding per vagina. In one-third to gonorrhea and Chlamydia; empirical treatment one-half of patients there is presence of an adnexal could be offered where this not possible. The diagnosis and management of ectopic Ectopic pregnancy pregnancy is described in Chapter 12. In Nigeria, the prevalence of ectopic pregnancy is 1 in 20 pregnancies in the southern cities and 1 in 17 Dysmenorrhea 50 in the northern cities. Abdominal pain is a cardinal feature of ectopic gestation, present in Painful menstruation interfering with normal activ- close to 100% of cases17,18. No specific symptoms or ity and requiring medication is referred to as dys- signs are indicative of ectopic pregnancy; a high menorrhea. It occurs in 30–50% of post-pubertal index of suspicion is needed to establish the diag- females and 10% are incapacitated for 1–3 days19. The triad of abdominal pain, amenorrhea and Symptoms of primary dysmenorrhea usually start bleeding in a woman of reproductive age should after menarche as initial cycles are usually anovular. Cyclic lower abdominal pain starting before and In low-resource settings about a third of patients predominantly during the first 2 days of the menses present as acute surgical emergencies19. It is usually not severe enough to tation and delay in diagnosis contributes to the warrant admission.
SHORT albuterol aerosol as maintenance therapy for asthma in adolescent and adult patients purchase erectafil once a day strongest erectile dysfunction pills. SHORT salmeterol in asthmatic patients with 24-hour spirometry and Holter monitoring purchase erectafil amex erectile dysfunction cure. Albuterol treatment for 6-POWDER children with asthma: a comparison of inhaled powder and aerosol cheap erectafil 20 mg without a prescription erectile dysfunction drugs boots. Kemp JP, Hill MR, Vaughan LM, Meltzer EO, Welch MJ, Ostrom NK. Clinical trial of metaproterenol aerosol in bronchial asthma. Quick-relief medications for asthma Page 96 of 113 Final Report Update 1 Drug Effectiveness Review Project Citation Exclusion Code Kesten S, Chapman KR, Broder I, et al. SHORT twice daily inhaled formoterol versus four times daily inhaled albuterol in the management of stable asthma. Effects of salmeterol on arterial blood gases in 6-LONG VS. SHORT patients with stable chronic obstructive pulmonary disease: Comparison with albuterol and ipratropium. Fenoterol inhalation powder and aerosol in the treatment of 6-POWDER asthma. Klusova EV, Semenovich NI, Polivanov EG, Pashkova TL. Berotek 1 treatment of bronchial asthma in combination with ischemic heart disease. A comparison of the effects of subcutaneous orciprenaline, 3 salbutamol and terbutaline in asthmatic children. Treatment of severe attacks of asthma in children with 6 nebulized B2 adrenergic agents. Kozlik-Feldmann R, von Berg A, Berdel D, Reinhardt D. SHORT effects of formoterol and salbutamol on bronchial hyperreactivity and beta-adrenoceptor density on lymphocytes in children with bronchial asthma. Kruse M, Rosenkranz B, Dobson C, Ayre G, Horowitz A. SHORT tolerability of high-dose formoterol (Aerolizer) and salbutamol (pMDI) in patients with mild/moderate, persistent asthma. Comparative study of inhaled salbutamol, 6 ipratropium bromide in chronic bronchitis. Comparison of the 5 bronchodilating effects of salbutamol delivered by a novel multiple dose dry powder inhaler or a conventional metered dose inhaler. Evaluation of a patient 5 questionnaire assessing the use of a novel multiple dose dry powder inhaler following a 4 week treatment with salbutamol. Clinical investigation 5 of a 4 week treatment with salbutamol delivered by a multiple dose dry powder inhaler or a conventional metered dose inhaler. Comparison of inhaled 6-POWDER terbutaline administered by either the Turbuhaler dry powder inhaler or a metered-dose inhaler with spacer in preschool children with asthma. Quick-relief medications for asthma Page 97 of 113 Final Report Update 1 Drug Effectiveness Review Project Citation Exclusion Code LaForce C, Prenner BM, Andriano K, Lavecchia C, Yegen U. SHORT and safety of formoterol delivered via a new multidose dry powder inhaler (Certihaler) in adolescents and adults with persistent asthma. LaForce CF, Ellis EF, Kordansky DW, Cocchetto DM, Sharp JT. Use 6-DESIGN and acceptance of ventolin Rotacaps and the Rotahaler in 1235 asthmatic patients. Bronchodilator effects of fenoterol and salbutamol 4 administered by intermittent positive pressure breathing to patients with asthma or chronic obstructive bronchitis. Bronchodilator effects of a fenoterol metered 6-POWDER dose inhaler and fenoterol powder in asthmatics with poor inhaler technique. SHORT albuterol in asthmatic patients receiving high-dose inhaled corticosteroids. Comparison of ipratropium bromide 6 and salbutamol in a long-term trial in asthmatic and bronchitic patients in a cold climate. The technology of metered-dose inhalers and treatment 6-DESIGN costs in asthma: a retrospective study of breath actuation versus traditional press-and-breathe inhalers. Salmeterol in the 5 prevention of exercise-induced bronchospasm in preschool children. Salbutamol: 6-POWDER comparison of bronchodilating effect of inhaled powder and aerosol in asthmatic subjects. Clinical efficacy and safety of Turbuhaler as compared to 6-POWDER pressurized MDIs-beta 2-agonists. Clinical and functional responses to 6-POWDER salbutamol inhaled via different devices in asthmatic patients with induced bronchoconstriction. A comparison of the duration of action 6-SAMPLE SIZE of fenoterol and salbutamol in asthma. Leblanc P, Knight A, Kreisman H, Borkhoff CM, Johnston PR. SHORT placebo-controlled, crossover comparison of salmeterol and salbutamol in patients with asthma. Lee DK, Jackson CM, Currie GP, Cockburn WJ, Lipworth BJ. Cardiac response to oral and aerosol 6 administration of beta agonists. Use of salbutamol powder in childhood 6-POWDER asthma. Quick-relief medications for asthma Page 98 of 113 Final Report Update 1 Drug Effectiveness Review Project Citation Exclusion Code Lenney W, Pedersen S, Boner AL, Ebbutt A, Jenkins MM. Therapeutic effect of inhaling berotec by oxygen engine 1 on bronchial asthma. Cost-effectiveness analysis of a dry 6-DELIVERY powder inhaler (Turbuhaler) versus a pressurised metered dose inhaler in patients with asthma. The efficacy of formoterol vs 5 salbutamol in emergency room asthma: a randomized controlled study. SHORT formoterol and salbutamol as asthma reliever medication in Sweden and in Spain. A high dose of albuterol does not overcome 6-LONG VS. SHORT bronchoprotective subsensitivity in asthmatic subjects receiving regular salmeterol or formoterol.
Disease-modifying drugs for multiple sclerosis Page 37 of 120 Final Report Update 1 Drug Effectiveness Review Project Table 12 generic 20mg erectafil visa erectile dysfunction caused by hernia. Characteristics of studies of beta interferons for secondary progressive multiple sclerosis Study name generic erectafil 20mg amex erectile dysfunction protocol scam or not, Year Interventions N Patient characteristics duration of follow-up Primary outcomes ® Interferon beta-1a IM (Avonex ) ® Mean age 48 yrs Interferon β-1a (Avonex ) Change in MSFC IMPACT 2002 Baseline EDSS 5 generic 20mg erectafil fast delivery erectile dysfunction natural herbs. Similar to the other studies, no significant difference was found using the Expanded Disability Status Scale time to progression measure (hazard ratio, 0. However, the larger study did find a benefit on annualized relapse rates and hospitalizations with both doses. While the rates of relapse were different between the 2 trials, the relative benefit of interferon beta-1a SC ® (Rebif ) were similar, with a pooled relative risk for yearly relapse of 0. The SPECTRIMS study found that women responded better to interferon ß1a SC (Rebif ) than men. These results are discussed in Key Question 3 below. Both studies were stopped early, based on planned interim analyses, but 82 for opposite reasons. In the European study the time to progression for the beta interferon 250 µg SC group was similar to that seen in the North American study (893 compared with 981 days, Disease-modifying drugs for multiple sclerosis Page 38 of 120 Final Report Update 1 Drug Effectiveness Review Project respectively), but the placebo groups differed (549 compared with 750 days, respectively). Pooled results indicated an overall benefit (see Table 13), and in further analysis those with active disease (higher relapse rates and greater progression at entry) appeared to benefit the most. In the SPECTRIMS study of interferon beta- ® 1a SC (Rebif ), a similar finding was observed. Making indirect comparisons across these trials in a qualitative way, there was evidence ® that interferon beta-1b SC (Betaseron ) is effective in slowing progression in patients with secondary progressive multiple sclerosis, particularly those with more active disease. Evidence ® ® for the beta-1a interferons (IM or SC; Avonex or Rebif ) was less convincing for slowing progression based on the Expanded Disability Status Scale, although the newer measure, the Multiple Sclerosis Functional Composite, allowed a benefit to be seen with interferon beta-1a IM ® (Avonex ). Whether this difference was clinically important and whether the other beta interferons would have a similar impact is not clear. Studies indicated that all of the beta interferons did have an impact by reducing relapse rates. Those with more active disease appeared to benefit more. Disease-modifying drugs for multiple sclerosis Page 39 of 120 Final Report Update 1 Drug Effectiveness Review Project Table 13. Results of studies of beta interferons for secondary progressive multiple sclerosis Study Name, Year Primary Outcomes Secondary Outcomes N Interferon vs. Total and psychosocial scores not different to placebo. While mixed results were found for disease progression, relapse rates were more consistently affected by the beta interferons. Four trials indicated that beta interferon therapy reduces relapse and associated hospitalizations in patients with secondary progressive multiple 2 sclerosis compared with placebo. Body surface area dosing (160 µg/m ) of interferon beta-1b SC ® (Betaseron ) was generally less effective than the 250 µg dose. Health-related quality of life was Disease-modifying drugs for multiple sclerosis Page 40 of 120 Final Report Update 1 Drug Effectiveness Review Project measured in 2 studies using different tools, both finding a benefit of the respective beta 79, 80 interferon used. Glatiramer acetate and natalizumab ® ® No studies of glatiramer acetate (Copaxone ) or natalizumab (Tysabri ) in patients with secondary progressive multiple sclerosis were found. Primary progressive multiple sclerosis Beta interferons Indirect evidence The primary evidence of the effectiveness of drug treatment in primary progressive multiple ® sclerosis came from a single small (N=50) trial of interferon beta-1a IM (Avonex ) at doses of 85 30 µg, 60 µg, or placebo once weekly for 2 years. While no statistically significant differences were found between the groups at baseline, the baseline Expanded Disability Status Scale in the placebo group was 1 point lower (4. The time to sustained progression (increase of ≥1 point on Expanded Disability Status Scale at baseline ≤ 5. There was no sample size calculation completed by the study authors; the small sample size and potentially clinically important differences at baseline left the possibility of benefit in a larger trial open to speculation. Statistically significant differences on secondary outcome measures (the 10-minute walk test and the 9-hole peg test) were also not found. However, the authors suggested that a benefit in right hand side 9-hole peg test was seen with the beta interferon 30 µg group (P=0. While a pilot trial of interferon beta-1b SC (Betaseron ) has been done, it has 86 only been partially reported to date. Details in this publication were inadequate for inclusion here. One systematic review by Rojas et al of the Cochrane collaboration reviewed data from 36 both of these trials including unpublished data from the pilot trial by Montalban. This trial data ® found a no significant differences between interferon beta-1b SC (Betaseron ) and placebo in sustained progression of disease and mean Expanded Disability Status Scale change over a 2 36 year period. The review pooled data from both interferons, which did not allow interpretation for comparative effectiveness, however, they found no difference in relapse related and disease progression outcomes when the data was pooled. These results were limited by the small number (N=143). Glatiramer acetate One indirect fair quality study, N=943, compared glatiramer acetate to placebo in patients with 87 primary progressive multiple sclerosis. The duration of the study was intended to be 36 months but was stopped early due to lack of efficacy. At that time 60% of patients randomized to Glatiramer and 59% of those randomized to placebo had received the study drug for 24 months, and 18% and 15% respectively had received the study drug for 36 months. The study found no significant difference in delay to sustained disability (hazard ratio, 0. Disease-modifying drugs for multiple sclerosis Page 41 of 120 Final Report Update 1 Drug Effectiveness Review Project Natalizumab and mitoxantrone No studies of natalizumab or mitoxantrone in patients with primary progressive multiple sclerosis were found. One study of glatiramer acetate included a mixed population (see below). Mixed populations: Clinically isolated syndrome and relapsing-remitting multiple sclerosis ® One small single-blinded head-to-head trial (N=75) comparing interferon beta-1b (Betaseron ) 57 to glatiramer acetate evaluated clinical exacerbations over 2 years as a secondary outcome. Randomization was stratified by clinical site and presence of enhancement on screening magnetic resonance imaging, which introduced bias to the results. There was no specific criterion for defining relapse, including change in Expanded Disability Status Scale and/or a decrease in the Scripps Neurological Rating Scale of at least 7 points, and a neurological examination was performed by a blinded examining neurologist. Most of the patients had relapsing-remitting multiple sclerosis (79%) with a baseline median annualized relapse rate and Expanded Disability Status Scale score of 1. No ® difference was found in the annualized relapse rate (interferon beta-1b [Betaseron ] 0. Because these were secondary outcomes, the study may not have had an adequate sample size (statistical power) to identify a statistically significant difference if one exists.