Meloxicam: clinical efficacy and safety.

#SYSTEMPHARM #UKRAINE

Pain syndrome is a very common manifestation in diseases of the musculoskeletal system. At various periods of life, pain associated with damage to the components of the musculoskeletal system occurs in 20-45% of the world’s population – more often in women than in men, and in older age groups (Nasonov, 2002). Pain syndrome negatively affects the patient’s quality of life and leads to significant socio-economic losses, so the treatment of this pathological condition is a very urgent issue.

Today, non-steroidal anti-inflammatory drugs (NSAIDs) occupy a central place in the treatment of pain. In rheumatology, NSAIDs are the main symptom-modifying agents for short-term and long-term therapy of many diseases, as well as drugs of choice for the initial therapy of arthritis of various origins. However, the increased risk of gastrointestinal (GI), cardiovascular, hepatic, and renal side effects when taking NSAIDs limits their use. Most of the adverse events described when taking NSAIDs are dose-dependent and are associated mainly with the blockade of cyclooxygenase 1 (COX-1), while the therapeutic effect is mainly due to inhibition of COX-2 activity. Therefore, an important development has been the development of selective COX-2 inhibitors, which are characterized by an improved safety and tolerability profile.

One of the most studied representatives of selective COX-2 inhibitors of NSAIDs is meloxicam. Meloxicam is a derivative of oxicamic acid, it has a long half-life: the maximum plasma concentration after taking 15 mg of the drug is reached after 7 hours, the half-life is 20-24 hours, so it is prescribed once a day at a dose of 7.5 or 15 mg, which is convenient for the patient. Meloxicam is structurally different from other COX-2 inhibitors in that it binds to the top of the COX-2 channel rather than to the side. Another important feature is its ability to bind to plasma proteins (99.5%) and easily penetrate into the synovial fluid, where its concentration is 45-57% of that in plasma. Meloxicam in the body does not interact with cytostatics, cardiac glycosides, diuretics and other drugs, which is of great importance for the safe treatment of people with concomitant diseases. The efficacy and safety of meloxicam has been studied in a number of large comparative clinical trials in osteoarthritis, rheumatoid arthritis and ankylosing spondylitis.

Osteoarthritis

Osteoarthritis is a chronic progressive joint disease of unknown etiology characterized by degenerative cartilage changes and bone proliferation, the clinical features of which include pain (both on movement and at rest), limitation of movement, swelling, and partial or complete loss of functional capacity of the affected joint(s). ). In the treatment of arthritis, NSAIDs are mainly used to reduce pain.

The efficacy of meloxicam in patients with osteoarthritis was studied in the MELISSA (Meloхicam Large Scale International Study Safety Assessment) and SELECT (Safety and Efficacy Large scale Evaluation of COX inhibiting Therapies) studies, in which the therapeutic activity of meloxicam (7.5 mg/day) was compared with that of diclofenac ( 100 mg/day) or piroxicam (20 mg/day). Meloxicam in its clinical efficacy was equivalent to diclofenac and piroxicam in terms of analgesic effect and improvement in the condition of patients, but surpassed them in tolerability.

At the annual European Congress of Rheumatology in Prague (EULAR, 2001), the results of a unique randomized study, Improve, were presented, which assessed the “therapeutic success” of meloxicam in osteoarthritis. The following parameters were taken to determine therapeutic efficacy (endpoint): completion of the study without switching to another NSAID, or completion of the study and no need to take an NSAID. According to the results obtained, the “therapeutic success” of meloxicam was observed in 66.8% of cases compared with 45% of patients taking other drugs (p < 0.0005). Patients in the meloxicam group were significantly more satisfied with the results of treatment. In addition, patients taking meloxicam were twice as likely to discontinue therapy compared to those who were prescribed other NSAIDs, suggesting that meloxicam has a better tolerability profile and a minimal number of undesirable effects.

Another clinical trial involving 229 patients with osteoarthritis of the lumbar spine compared the effectiveness of diclofenac (100 mg/day in the form of sustained release tablets) and meloxicam (7.5 mg/day). The results obtained indicate the same effectiveness of these drugs in eliminating pain, however, when taking meloxicam, better tolerability was noted. The frequency of side effects from the digestive tract, as well as refusals of treatment when prescribing meloxicam, was significantly lower (Valat et al., 2001).

Rheumatoid arthritis

Rheumatoid arthritis is a chronic autoimmune systemic inflammatory disease of the connective tissue with a predominant lesion of the joints in the form of erosive-destructive progressive polyarthritis. The disease affects 0.5-1% of the population. The exact cause of rheumatoid arthritis is unknown.

Several studies have shown that meloxicam is as effective as diclofenac, piroxicam and naproxen in patients with rheumatoid arthritis (Wojtulewsky et al. 1996; Huskinsson et al. 1996). In a double-blind comparative trial of meloxicam and naproxen, the efficacy of both drugs was approximately the same, but meloxicam was better tolerated in the gastrointestinal tract and kidneys (Wojtulewsky et al. 1996). In the work of E.C. Huskinsson et al. it was shown that in the treatment of 357 individuals with rheumatoid arthritis with meloxicam at a dose of 15 mg / day after 18 months of observation, the total indicator of pain activity on the visual analogue scale decreased from an average of 3.32 to 2.33 cm. stiffness and Ritchie index. Only 11.4% of patients discontinued treatment due to lack of efficacy and 13.7% due to adverse reactions, which included gastrointestinal, musculoskeletal, skin and respiratory disorders. Severe side effects, such as gastric ulcer with bleeding or perforation, were noted only in

3 patients (0.8%). Thus, in the long-term treatment of inflammatory joint diseases, meloxicam is not inferior in effectiveness to standard NSAIDs and clearly outperforms them in tolerability.

Ankylosing spondylitis

Ankylosing spondylitis (Strümpel-Bekhterev-Marie disease), or Bekhterev’s disease, is a chronic systemic disease of the joints with a predominant localization of the process in the sacroiliac joints, joints of the spine and paravertebral soft tissues. The prevalence of ankylosing spondylitis varies widely and mainly depends on the frequency of occurrence of a particular genetic marker of the HLA-B27 antigen.

In patients with osteoarthritis, the efficacy of meloxicam was studied in a randomized, double-blind, placebo-controlled study compared with piroxicam, which has a long half-life and is highly effective in individuals with ankylosing spondylitis (Dougados et al., 1999). A feature of this study was a longer period of use of comparator drugs (12 months) than in others, which is very important for an objective assessment of their tolerability. Meloxicam was used at doses of 15 and 22.5 mg, and piroxicam at 20 mg. The authors of the study concluded that in patients with ankylosing spondylitis, it is more appropriate to use meloxicam at a dose of 22.5 mg/day, both in terms of efficacy and tolerability.

Recently, works have appeared where NSAIDs are considered as drugs that can actively influence the mechanisms of the pathological process and the rate of radiological progression. This point of view has found its evidence in the treatment of ankylosing spondylitis (Mielants, Cruyssen, 2006).

Portability

Given the fairly widespread use of NSAIDs, the prevention and treatment of undesirable complications associated with their use is one of the most urgent problems of modern medicine. Meloxicam is well researched in terms of efficacy and tolerability. This is confirmed by the data of a meta-analysis of 10 randomized trials involving more than 20 thousand patients (Schoenfeld, 1999).

Gastrointestinal tract

Compared with classical NSAIDs (diclofenac, ibuprofen, piroxicam), selective COX-2 inhibitors are characterized by a lower risk of gastrointestinal side effects with comparable efficacy. Thus, in two large prospective comparative studies MELISSA and SELECT, which studied the safety of meloxicam in patients with osteoarthritis, it was shown that treatment with this drug was associated with less toxicity to the gastrointestinal tract, a lower risk of developing peptic ulcers and associated bleeding than therapy with diclofenac and piroxicam. A meta-analysis of all randomized comparative clinical trials of meloxicam published in 1990-1998 showed a significant advantage of using meloxicam over other NSAIDs in relation to the risks associated with the gastrointestinal tract (Schoenfeld, 1999). In particular, patients receiving meloxicam showed a significant reduction in the risk of side effects such as dyspepsia, ulcer perforation and bleeding (relative risk [RR] 0.64; 95% confidence interval [CI] 0.59-0.69) according to compared with non-selective NSAIDs. Data from the recent IMPROVE clinical trial (2001) and a new meta-analysis involving a significant number of patients confirmed the favorable safety profile of meloxicam in relation to effects on the gastrointestinal tract (Degner et al., 2001).

Meloxicam occupies a unique place among other NSAIDs: it does not have a toxic effect on the gastrointestinal tract, like other selective COX-2 inhibitors, and is characterized by a high level of safety from the cardiovascular system. This was proven in a large meta-analysis involving more than 27 thousand patients in whom the use of meloxicam did not contribute to an increase in cardiovascular risk, and the frequency of cardiovascular events (including heart attack and stroke) was comparable to that when taking non-selective NSAIDs (including aspirin, cardioprotective at low doses) (Singh et al., 2001). In a more recent large-scale study by R. Altman et al. (2002), showed the advantage of meloxicam therapy in preventing acute coronary events in individuals with diseases of the cardiovascular system compared with that of other NSAIDs.

Conclusions

Thus, meloxicam is an effective drug from the group of selective NSAIDs, which has a pronounced anti-inflammatory and analgesic effect and an optimal safety profile in relation to the gastrointestinal and cardiovascular systems, kidneys and liver. The drug is well tolerated by almost all patients and is recommended in the treatment of diseases such as osteoarthritis, osteoarthritis, ankylosing spondylitis, as well as postoperative pain and other pain syndromes.

Information from the medical journal “NeuroNews: Psychoneurology and Neuropsychiatry” – the first in Ukraine journal of psychiatry and neurology for specialized practitioners.

Among the products of the SYSTEM PHARM company are presentations to PHARMAXICAM – meloxicam in injection bottles. 1 vial 1.5 ml mixed with 15 mg meloxicam.

Indications

Short-term symptomatic treatment of an acute attack of rheumatoid arthritis and ankylosing spondylitis.

Application

One injection of 15 mg once a day.

Store the bottles in their original package at a temperature not exceeding 25°C. Do not freeze. Keep out of the reach of children.