• 23
    Jun
  • Interferon 3-la in the Treatment of Multiple Sclerosis: CLINICAL TRIALS

In a randomized, double-blind, placebo-controlled study (PRISM-2) of interferon | -1a in patients with RRMS, 560 participants were randomly assigned to receive subcutaneous interferon | -1a 22 mcg (n = 189), 44 mcg (n = 184), or placebo (n = 187) three times a week for two years. The mean number of relapses during the two years of the study was lower in both interferon | -1a groups than in the placebo group (P < .005). The percentage reduction for the patients receiving the 22-mcg dose, compared with those receiving placebo, was 27% (95% confidence interval [CI], range, 14%-39%), and the percentage reduction for patients receiving the 44-mcg dose, compared with those patients receiving placebo, was 33% (range, 21%-44%). The mean number of moderate and severe relapses during the two-year follow-up period was also lower in both interferon P-1a groups than in the placebo group (P < .005). The median time to first relapse was delayed by three and five months in the groups receiving 22 mcg and 44 mcg, respectively.

After the first year of treatment, relapse rates were lower for those receiving 22 mcg and 44 mcg of interferon | -1a than for those receiving placebo (P < .0001). The time to sustained progression in disability was significantly longer (P < .05) in both interferon | -1a treatment groups than in the placebo group (Table 1).
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Table 1    Time (in Months) to Confirmed Progression* in Disability for Patients with Multiple Sclerosis

Placebo (n = 187)

Interferon P-1a 22 mg (n = 189)

Interferon P-1a 44 mg (n = 184)

All patientsFirst quartile time to progression (months) Risk ratio (95% CI)

11.9 1.00

l8.5j 0.58 (0.48-0.96)j

2l.3j

0.62

(0.43-0.9l)j

Group with high baseline EDSS (>3.5)First quartile time to progression (months)

Risk ratio (95% CI)

7.3 1.00

7.5 0.75(0.35-l.56)

21.3

0.42 (0.l8-0.99)

* Progression = one or more steps in the Expanded Disability Status Scale (EDSS), sustained for at least three months. j P < .05 compared with placebo. CI = confidence interval.Adapted from PRISMS Study Group. Randomized double-blind placebo-controlled study of interferon P-la in relapsing /remitting multiple sclerosis. Lancet 1998;352(9139)1498-1504.5

Magnetic resonance imaging (MRI) showed a progressive median increase of 10.9% in the number of lesions in placebo-treated patients but decreases of 1.2% and 3.8% in the groups receiving 22 mcg and 44 mcg of interferon p-1a, respectively (P < .0001), compared with those taking placebo for both doses. The number of active lesions was significantly lower in the patients receiving 22 and 44 mcg of interferon | -1a than in those receiving placebo (P < .0001). In patients receiving the 44-mcg dose, the number of lesions was significantly lower than in patients receiving 22 mcg (P= .0003).

PRISMS-4, an extension of the PRISMS-2 study, was conducted to determine the long-term efficacy of interferon p-1a in patients with relapsing MS. Four years of treatment with interferon | -1a at doses of 22 mcg or 44 mcg significantly reduced the number of relapses per patient per year, compared with two years of placebo treatment followed by two years of interferon | -1a therapy. The smaller number of relapses per patient per year (over four years) in the 44-mcg group versus the 22-mcg group approached significance (P= .069).
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During years three and four, relapse rates were significantly lower for the group receiving 44 mcg than for the other groups. The relapse rate decreased progressively with each year of therapy, with values of 0.92, 0.82, 0.57, and 0.44

relapses per year for the 0.44-mcg group during years one through four. The relapse rates for placebo in the patients receiving 22 mcg were 1.3 during years one and two and 0.63 in years three and four (95°% CI, 36%-63%; P < .001). Rates for placebo/44 mcg were 1.29 and 0.68 (95% CI, 31%-61%; P < .001).

In the three-group intent-to-treat analysis, the proportion of patients who were free from relapses after four years was greater in those taking 44 mcg (19%) and 22 mcg (14.4%) than in the crossover groups combined (6.7%; P< .001 crossover vs. 44 mcg; P = .016 crossover vs. 22 mcg).

The time to first confirmed progression did not differ significantly between the 22-mcg group (35.9 months) and the crossover group (P = .289) or between the 44-mcg group and the 22-mcg group (P = .33).

In the PRISMS-2 trial, 61.7% of patients taking placebo were free from MS progression, compared with 70.3% for the patients receiving 22 mcg and 73.2% for the patients receiving 44 mcg. In the PRISMS-4 trial, 46% of the crossover group, 51% of the 22-mcg group, and 56% of the 44-mcg group remained free from progression (P = .070). Patients receiving 22 mcg and 44 mcg had fewer new lesions than did the crossover group combined (P< .001 in each case), and the 44-mcg group had fewer new lesions than did the 22-mcg group (P< .001).

The proportion of scans showing new lesions over four years was also lower in the patients receiving 44 mcg of interferon |3-1a than in the patients receiving 22 mcg (P < .001). The proportion of scans showing active lesions was lower for crossover patients in both dose groups (P < .001) after patients were switched to the active drug, compared with their years of receiving placebo.

In years three and four, the median number of new lesions per patient per MRI scan and the proportion of scans showing new lesions were lower for those receiving 44 mcg of interferon |3-1a than for either the placebo/44 mcg or 22 mcg (P< .001 in each case). There were no significant differences between the 22-mcg and placebo/22-mcg groups.

Adverse events during the extension study were similar to those observed in the PRISMS-2 trial, and most of these were mild. The onset of adverse events during years three and four was higher in the crossover groups. During years three and four, 23% and 29% of patients, respectively, reported depression at least once. In PRISMS-2, patients receiving placebo reported depression more often than patients receiving inter-feron |3-1a.

Additional studies support the findings in this article and the positive effects of interferon |3-1a in the treatment of MS. kamagra oral jelly uk

CONCLUSION

MS is a chronic, incapacitating illness that is difficult to diagnose. Neurological findings, clinical observation, examination of spinal fluid, MRI results, and sometimes tests of evoked potentials constitute the basis for diagnosis. No curative treatment is currently available for MS, but several medications can be used to treat the disease symptomatically. Interferon |3-1b and |3-1a have been used successfully to reduce the frequency and severity of relapses.

MS research has evolved tremendously in the last decade, and our knowledge of this disease is increasing. This understanding will expedite the development of new treatments to improve the quality of life of patients with MS.

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