Chapter 27 Research to Suppress Rebound - 1
Olopatadine hydrochloride suppresses the rebound phenomenon after discontinuation of treatment with a topical steroid in mice with chronic contact hypersensitivity
By T. Tamura et al. published in the Clinical & Experimental Allergy, Volume 35, Number 1, January 2005 , pp. 97-103(7)
Kyowa Hakko Kirin Co., Ltd. sells anti-allergic agent called ALLELOCK. This study confirmed ALLELOCK could inhibit the rebound phenomenon experimentally developed on mice by making them addicted to steroids and then stopped the application. Tadafumi Tamura seemed to belong to a research laboratory of the company.
Oxazolone was topically applied on the mouse ears and then ear thickness was monitored. Oxazolone, which is known to cause allergic contact dermatitis accompanied by T cell shifting from Th1 to Th2 dominance and IgE increase as revealed by a blood test, is appropriate to make an atopic dermatitis (AD) model.
Olopatadine hydrochloride suppresses the rebound phenomenon after discontinuation of treatment with a topical steroid in mice with chronic contact hypersensitivity
By T. Tamura et al. published in the Clinical & Experimental Allergy, Volume 35, Number 1, January 2005 , pp. 97-103(7)
Kyowa Hakko Kirin Co., Ltd. sells anti-allergic agent called ALLELOCK. This study confirmed ALLELOCK could inhibit the rebound phenomenon experimentally developed on mice by making them addicted to steroids and then stopped the application. Tadafumi Tamura seemed to belong to a research laboratory of the company.
Oxazolone was topically applied on the mouse ears and then ear thickness was monitored. Oxazolone, which is known to cause allergic contact dermatitis accompanied by T cell shifting from Th1 to Th2 dominance and IgE increase as revealed by a blood test, is appropriate to make an atopic dermatitis (AD) model.
The X-axis value indicates the experiment date that begins with 0 and the Y-axis value indicates ear thickness (swelling). In all subjects, oxazolone was topically applied 3 times a week. The ●-line represents the control group. The ▲-line represents the group in which steroid was topically applied. The △-line represents the group in which steroid was used from Day 0 till Day 17 and then discontinued on Day 18. On Day 30 and thereafter, the △-line rose beyond the ●-line, which means rebound had occurred. (This is an animal model for steroid addiction.)
The □-line represents the group in which systemic application of 10mg/kg/day ALLELOCK (olopatadine) was begun on Day 18 when steroid was discontinued.
The 10 mg/kg/day dose is equivalent to 500 mg/day for a 50 kg person if based on the weight (50 times more than the usually recommended dosage of 10mg for adults). However, considering the body surface ratio, the effect for human beings will be one ninth of that for mice. Therefore, this dosage is considered 5.5 times more than the usual dosage (50×1/9=5.5)
On Day 30 and thereafter, the □-line is below the ●-line and it can be said that rebound has been suppressed.
The 10 mg/kg/day dose is equivalent to 500 mg/day for a 50 kg person if based on the weight (50 times more than the usually recommended dosage of 10mg for adults). However, considering the body surface ratio, the effect for human beings will be one ninth of that for mice. Therefore, this dosage is considered 5.5 times more than the usual dosage (50×1/9=5.5)
On Day 30 and thereafter, the □-line is below the ●-line and it can be said that rebound has been suppressed.
The above graph shows the IL-4 measurements of the blood taken on Day 38. Ace represents the control group in which acetone was topically applied (acetone is used as vehicle for oxazolone), Ox represents the group in which oxazolone was topically applied, Olo represents the group in which ALLELOCK (olopatadine) was systemically used, and Pred represents the group in which predonine (steroid) was topically applied. As to the group in which predonine was topically applied during Day 0-17 and discontinued during Day 18-37 (bar graph in the center) or the group in which predonine was topically applied and olopatadine was systemically used during Day 0-17 and disucontinued during Day 18-37 (the second bar from the right), IL-4 measurements are higher than the Ox group. (It is confirmed that the phenomenon similar to that found in human rebound has occurred.)
The above graph shows serum IgE increased significantly in the group continuously treated with the steroid (Pred or Pred/Olo) compared to the Ox group. It increased more when the steroid was discontinued (which is considered rebound).
These results resemble the data Dr. Kimata showed in his study that concluded IPD could suppress rebound (see Chapter 20). I wondered if IPD is enough to suppress rebound and dared to ask him. His answer was that the subjects used in his study might be classified into mild cases of addiction. For rebound in mild addiction cases, anti-allergic agents such as IPD or ALLELOCK may be effective. In this study, rather weak steroid (Prednisolone) was applied for only 17 days and resulting rebound was probably not so severe.
Japanese drug makers are also examining their products for the effectiveness against steroid addiction to report in overseas magazines. However, their studies are not often made use of at Japanese clinics or hospitals.
For the dermatologists who are influential in the Japanese Dermatological Association (JDA) because they prepare its guidelines, stick to the unscientific stance of denying the phenomenon of steroid addiction.
As a result, patients as well as young clinical doctors suffer a disadvantage.
These results resemble the data Dr. Kimata showed in his study that concluded IPD could suppress rebound (see Chapter 20). I wondered if IPD is enough to suppress rebound and dared to ask him. His answer was that the subjects used in his study might be classified into mild cases of addiction. For rebound in mild addiction cases, anti-allergic agents such as IPD or ALLELOCK may be effective. In this study, rather weak steroid (Prednisolone) was applied for only 17 days and resulting rebound was probably not so severe.
Japanese drug makers are also examining their products for the effectiveness against steroid addiction to report in overseas magazines. However, their studies are not often made use of at Japanese clinics or hospitals.
For the dermatologists who are influential in the Japanese Dermatological Association (JDA) because they prepare its guidelines, stick to the unscientific stance of denying the phenomenon of steroid addiction.
As a result, patients as well as young clinical doctors suffer a disadvantage.