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Using of differnt medicinal forms of inhibitors cox-2 in the treatment of patients with osteoarthritis institute of cardiology, kiev

The Resume.
The efficiency of selective inhibitor COG-2 of NIMULID was analyzed in treatment of patients with osteoarthritis. For an estimation of the efficiency were used the indexes to gravity of Laquesne; the visual scale of pain; articular, painful and inflammatory indexes of Richi.; volume of the movement in joints; the estimation to the efficiency of the treatment on 4-points scale. On 5 - 15-th day of the treatment it was managed to reach the significant reduction of evidence pain and inflammatory syndrome, improvement of functions of the affected joints. Tolerance of the preparation was regarded as good. All the patients have finished the examination, 5 of them had gastralgia that not required canceling of the preparation.


INTRODUCTION

Osteoarthritis (OA) is the most wide-spread disease of joints, in its base is the defeat of the joint gristle with involvement in process subchondral bone plate and reasonably expressed synovitis. The development of osteoarthritis is consequent of mechanical interaction and biological factors, which brings to violation of balance between dehydrase and syntheses matrix of the joint gristle and subchondral bone. At the same time the gristle is softened, its tissue is partly forfeited, subchondral sclerosis is developed ( Moiseev B.C., 1998). Synovil membrane, fibroid capsule, surrounding joint of the muscle are involved also in pathological process. OA is noted in 10-12% of the population, moreover the disease increases of the age. As a rule, each person senior 80 has the signs of deforming arthrosis of large joints and spine (Kotelnikov G., Chernov A., 2000). According to the literature, 80% of the all joint pathologies constitute degenerative dystrophic disease of joints, 37% of the patients that reside on the stationary treatment because of diseases of bone-muscular system, have OA. About 30% of the patients with prescribed disablement in consequence of joint disease form sick by OA. On frequency of affection the first place occupies the hip joint (42,7%), the second - knee joint (33,3%), the third - shoulder joint (10,8%), on the fourth - other joints (13,2%) (Kotelnikov G., Chernov A., 2000).The urgency of OA problem is concluded in degenerative dystrophic disease of joint, more frequent it is pathology, concerning which the patients ask for medical aid. The manifestations of pain syndrome is so varied, that the doctors of different specialty are engaged in this problem. At present the main group of medicinal facilities, used in treatment of OA, it is nonsteroid anti-inflammatory preparations (NAIP). Their prescription is justified pathogenetic, as synovitis frequency is high and it is important the role of the inflammatory process in progress of disease (Moiseev B. C., 1998). Anti-inflammatory effect of NAIP basically is connected with inhibition of cyclooxygenase (COG) -a ferment, that catalyzes formation of endoperoxidase, prostaglandin Gg and Hg from arachidonic acid. In reaction, that is catalyzed by COG, endoperoxidase later on metabolizes in number of eicosanoids that includes prostaglandin Eg (PGEz) - the main mediator of local inflammatory process (Portanova J. P., 1996). At present it is known two isoforms of COG. COG-1is a ferment, that constantly presents in many tissues of an organism and in the first place is responsable for production of PG, participating in normal homeopathic process (Bowles J. T., 1998). COG-2 is inducible ferment, that is formed in the central of the inflammation and promotes biosynthesis PGEa. In healthy tissues it is found in low concentration. Since the time of the opening two isoforms COG it is established that the development of side effects (gasropathy) is caused by inhibition of isoenzyme COG-1 (Simon LS., Yocum D., 2000). The works of the last years have allowed to synthesize the selective inhibitors isoenzyme COG-2. One of the representatives of the preparation of this group is NIMULID (nimesulid) produced by the company “ Panacea Biotec”, its efficiency and tolerance were analyzed on the basis of separation noncoronarogen diseases and clinical rheumatology of the Cardiology Institute n. N. D. Strazshesko.


OBJECT AND METHODS OF THE INVESTIGATIONS

60 patients were examined (47 women and 13 men) with different forms of OA during 6 month - 20 years (on the average 5,97±3,8 years). The age of the patients has fromed 44 to 81 (on the average - 57,6±9,6 years). The patients were divided on two groups - the main (the first) and control (the second). The main group has formed 30 patients (table 1), 17 of them had diagnosis of mono- or oligoarthritis of knee joints, 13 had polyosteorthrosis (POA) with primary affection of knee joints. Depending on rontgenological stage patients of the main group were arranged on three subgroups. 7 patients entered in the first subgroup (6 women and 1 man) their age formed on the average 50,7±7,1 years duration of disease was 2,1±1,1 year. 2 of them had diagnosis of monoarthritis of knee joint of the 1-st rontgenological stage, 5 had monoarthritis of knee joint of the 2-nd rontgenological stage. 13 patients were enclosed in the second subgroup (11 women and 2 men), their average age formed 57,2±7,3 years, duration of disease was 4,5±1,9 year. All the patients of this subgroup had POA of the 2-nd rontgenological stage, 3 of them had affection of hip joint of the 2-nd rontgenological stage. 10 patients were included in the 3-rd subgroup ( 7 women and 3 men ), their age formed on the average 66,6±8,8 years, duration of disease was 12,2±3,2 years. All the patients of this subgroup had diagnosis of POA with primary affection of knee and hip joints of the 3-rd rontgenological stage.


30 patients entered in control group (23 women, 7 men) of the age from 44 Clinical description of the patients with OA, which took to 67 years (at the average - 56,4±7,8 years) with duration of the disease from 2 to 9 years (on the average - 5,4±1,8 year). 23 patients of control group had diagnosed mono-oligoarthritis of knee joints, 7 had POA, 22 had OA of the 2-nd rontgenological stage, 8 had OA of the 3-rd rontgenological stage. The patients of the main group were taking inside NIMULID in dose 100 mg 2 times per day during 14 days, patients with mono- and oligoarthritis of knee joints of 1-st 2-nd rontgenological stage in addition local used NIMULID gel. The patients of control group took inside diclofenac, daily dose was 100 mg in 2 intake during 2 weeks.


Table 1 NIMULID

INDEX SUBGROUP
1 2 3 All patients
Number patients 7 13 10 30
Women 6 11 7 24
Men 1 2 3 6
Average duration of disease, years 2,1 ± 1,1 4,5 ± 1,9 12,2 ± 3,2 6,5 ± 4,2
Affection of joints
Hip 0 3 10 13
Knee 7 10 10 17
Rontgenological stage
1 2 0 0 2
2 5 13 0 18
3 0 0 10 10


THE RESULTS AND THEIR DISCUSSION
In the first subgroup of the main group was noted the best efficiency of the investigating preparation: positive dynamics, since the first day of reception, and maximal effect to the 5-th day, saving till the end of the treatment. For achievement of firm effect it took no less than 10 days of treatment of NIMULID for the patients of the second subgroup. Moderate reduction of painful syndrome was noted in the third subgroup by the end of the second week of the intake of preparations. The index Lequesne. The estimation of the function condition was conducted with use of algofuncional indexes of gravity gonarothrosis and cocxarthrosis by M. Lequesne (table 2). It was noted clear positive dynamics of the index of Laquesne, the most expressed had the patients of the first and second subgroups.


Table 2 Dynamics indexes of heaviness Lequesne

DIAGNOSIS SUBROUP
on average first second third
Gonarthrosis before treatment 18,5 ± 1,3 19,0 ± 1,1 18,7 ± 0,9 18,1 ± 1,7
after treatment 12,7 ± 1,7 13,4 ± 1,6 12,8 ± 1,7 12,1 ± 1,8
r <0,001 <0,001 <0,001 <0,001
Cocxarthrosis before treatment 14,9 ± 2,4   10,0 ± 2,0 16,4 ± 1,4
after treatment 9,9 ± 1,8   6,7 ± 1,8 10,9 ± 1,4
r <0,0001   <0,09 <0,001


THE VOLUME OF THE MOVEMENT IN JOINTS
On background of the reception of the preparation NIMULID the volume of movement for certain increased in affection joints at all the patient of the first and second groups, moreover, it reached the factors in rate at the patients of the first subgroup and partly second subgroup. The volume of the movement in knee joints for certain increased in the third subgroup. The tendency to increasing of prevention external and internal rotation in hip joints (r<0,05) was noted. As the patients of the third subgroup had a heavy inconvertible changes of the joint gristle, synovial membrane and subchondral bone, significant narrowing of joint space and big duration of the disease, the efficiency of investigating preparation turned out to be insufficient. Joint, painful and inflammatory indexes of Richi. All the patients had reliable positive dynamics of indexes of Richi. Painful index fell on the average on 53%, joint index fell on 68%, inflammatory index fell on 65%. The most essential positive dynamics symptoms of synovitis in joints was noted under additional using of NIMULID gel.


THE ESTIMATION OF PAIN SYNDROME ON
Evidence of pain syndrome on constantly, vastly and realistically fell for the whole period of the treatment (14 days) on average at all the patients so and on groups, the patients of the first group had it more expressive. To the 5-th day of treatment the evidence of pain fell on 82%, from 5,5 to 1 point. The patients of the second subgroup also had good results: to the 10-th day the severity of pain syndrome fell on 49%, from 6,8 to 3,5 points and continued to fall, forming 2,5 points to the 14-th day of the treatment. The patients of third group had less expressed dynamics of pain syndrome: initial is 8,3 points, to the 14-th day - 4,8 points. So, on the background of the treatment course by NIMULID evidence of pain syndrome on fell at the average on 59%, among the patients of all three subgroups: in the first fell on 89%, in the second fell on 65%, and in the third fell on 34%. The estimation of the treatment by the doctors and the patients. In the first subgroup the estimation of the doctor and the patients practically coincided, in the second and in the third subgroup the estimation of the doctor was higher on 0,25 and 0,5 points accordingly. All the patients which in addition applied NIMULID helium to knee joints, noted expressed local analgetic and anti-inflammatory action of the preparation.


THE SIDE EFFECTS
All the patients, which were included in the investigation, had terminated the treatment. Tolerance of NIMULID was good. During the first days of the intake 5 patients noted gastralgia, that was independently stopped without prescription of antacid preparations. The comparative estimation of efficiency of preparation NIMULID and diclofenac sodium. Compared groups of the patients were similar on the basic of clinicodemographic factors. On the background of the treatment more denominated anti-inflammatory effect was reached in the main group: reliable differences of the value of index Lequesne (r<0,05), joint and inflammatory index of Pichi (r<0,05).At the estimation of the analgesic effect and volume of the movement in knee joints reliable differences between compared groups was not revealed (r<0,05). As a whole taking into consideration influences upon evidence of pain and inflammatory syndrome, as well as side efficiency of NIMULID evaluated by the doctor and the patients was a little higher than diclofenac sodium.

CONCLUSION

  1. The advantages of NIMULD are the forms of the issue - tablets and gel. Their multifunctional prescription raises the efficiency of the preparation and reduces the dose of the system application.
  2. Selective inhibitors COG-2 possess the big type of safety in contrast with taking NAIP at present time, because it does not influence upon physiological syntheses of prostaglandin in the ventricle and kidneys (controlled by COG-1), and consequently, they have less expressive negative influence upon digestive tract and kidneys.
  3. One of the ways of reduction the risk of NAIP caused by gastropathy is a local application of preparations of this group, which is the most efficient under mono- and oligoarthritis and can be used as independently, so and in combination with other medicines.

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