Patients were randomized separately based on their pain status at baseline. Efficacy evaluations were conducted in the per-protocol analysis PPA population and in the modified intent-to-treat MITT population; safety evaluations were conducted in the safety population.
Both the MITT and safety populations included all patients who were randomized and received at least one dose of study drug. The PPA population was the subset of the MITT population who had no major protocol violations and completed all four visits, including at baseline. The study was conducted in compliance with the ethical principles originating in, or derived from, the Declaration of Helsinki and in compliance with the Independent Review Boards at each participating centre, informed consent regulations and International Congress of Harmonisation Good Clinical Practice Guidelines.
In addition, all local regulatory requirements were followed. Written informed consent was obtained prior to the patient entering the study e. The trial was registered with ClinicalTrials. The treatment period was 6 weeks. Other secondary objectives included change in Western Ontario and McMaster Universities WOMAC Osteoarthritis Index from baseline to week 6 and the Pain Satisfaction Scale comprising 11 questions on information about pain and its treatment, and pain medication in general at week 6.
All pairwise comparisons were conducted. Safety analyses were evaluated in the safety population patients who were randomized and received at least one dose of study medication. Demographic and baseline characteristics were similar across the three treatment groups Table 1. The mean age was A total of patients received at least one dose of study medication and had at least one post-baseline OA pain assessment, and comprised the MITT population Figure 1.
Of the patients in the MITT population, a total of patients completed the study i. The remainder of the patients were either withdrawn for other reasons i. There were no patient deaths during the study. The LS mean decrease in the ibuprofen group was not significantly different from that seen in either the placebo or celecoxib group.
At week 6, a greater proportion of patients in the celecoxib group At week 6, a greater proportion of patients in the celecoxib There were significant improvements in total WOMAC OA score and individual domain scores in the celecoxib and ibuprofen groups compared with placebo Figure 2b.
A greater proportion of patients in the celecoxib and ibuprofen groups than in the placebo group agreed with the Pain Satisfaction Scale questions Table 3. Patients treated with celecoxib were significantly more satisfied than those receiving placebo on 10 of the 11 Pain Satisfaction Scale questions, including those related to duration and onset of pain relief; effect on physical health; outlook on life; ease in performance of daily activities and leisure activities; improving independence, relationships with others and mood; and allowing easier movement.
A total of patients reported treatment-emergent AEs Table 4. The incidence of treatment-emergent AEs was A total of 20 patients discontinued the study because of treatment-emergent AEs. There were no deaths, but one patient a year-old female receiving concomitant aspirin and with a history of cardiac arrhythmia in the ibuprofen group experienced two serious AEs aggravated hypertension and congestive heart failure , considered by the investigator to be unrelated to study medication.
There were no serious AEs in the celecoxib or placebo groups. Dyspepsia, abdominal pain and upper gastrointestinal events were reported by more ibuprofen-treated patients, whereas diarrhoea was reported by more celecoxib-treated patients.
Although the efficacy of celecoxib compared with diclofenac and naproxen in relieving pain and improving physical function in patients with OA has previously been established, 16 — 21 to date there has been little direct evidence comparing celecoxib with ibuprofen, despite ibuprofen being one of the most commonly used NSAIDs. In this present study, both active treatments resulted in significant improvements, compared with placebo, in the pain, physical function and total domains of the WOMAC OA Index.
This is consistent with previous indirect comparisons between celecoxib and ibuprofen that have suggested they have comparable efficacy. In a chronic disease such as OA, it is particularly important to assess the degree of patient satisfaction with treatment.
Given the changes in symptom severity over time, together with the occasional need to switch treatments, based on reduced efficacy or tolerability, patient satisfaction may be a more accurate measure of the overall effectiveness of a treatment.
Patients receiving ibuprofen were significantly more satisfied than those receiving placebo on only three of the 11 measures. These results suggest that, in general, patients receiving celecoxib were more likely to be satisfied with their treatment than patients receiving ibuprofen. It has been suggested that, because patient perception of the effectiveness of a treatment can be an indication of its suitability, measures of patient satisfaction should be included in clinical trials and in the overall evaluation of any treatment.
However, a previous trial demonstrated that improvements in pain and patient and physician perceptions that were apparent after 6 weeks were maintained for up to 12 weeks of celecoxib treatment. Celecoxib was well tolerated compared with placebo and ibuprofen.
The proportion of patients with an upper gastrointestinal event was higher with ibuprofen than with celecoxib.
Given the low number of events in this study, the lack of a significant difference between active treatment groups is not surprising.
However, this trend is consistent with the findings from pooled and meta-analyses, which have suggested that there is a lower risk of gastrointestinal events with celecoxib than with ibuprofen or other NSAIDs. However, the FDA was in a dilemma. Celebrex was still on the market and other COX-2 inhibitors were in late-stage development. This meeting lasted three days and consisted of 30 advisors—an unusually high number. It covered the gamut of the properties of COX-2 inhibitors in order to understand the risk-benefit balance that these drugs posed to patients.
At the end of these sessions, the joint committee voted to allow Celebrex to stay on the market as it became clear that long-term use of other NSAIDs also posed CV hazards. The FDA agreed with this recommendation. As a result, the FDA made the following change to the Celebrex label:. Celebrex may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction and stroke, which can be fatal.
This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. While this solved the immediate problem, the FDA now had a bigger issue. Patients with arthritis tend to be older, heavier and not easily able to exercise due to joint pain—the very patients that are prone to heart disease. How should physicians be advised as to best treat arthritis pain in this population?
JRA is also called juvenile idiopathic arthritis. A drug class is a group of medications that work in a similar way. Celebrex contains the active ingredient celecoxib. Celebrex comes as a capsule that you swallow. You can also open the capsule and sprinkle the contents on a spoonful of applesauce to swallow.
Celebrex is available in four different strengths: 50 milligrams mg , mg, mg, and mg. Celebrex is a nonsteroidal anti-inflammatory drug NSAID that reduces inflammation swelling and damage and relieves pain. Types of acute pain that can be treated with Celebrex include:. The drug has been widely used to treat acute pain since it was first approved in For example, NSAIDs such as Celebrex are recommended in guidelines for treating pain following musculoskeletal injury.
NSAIDs are also recommended in guidelines for treating back pain. OA is the most common form of arthritis. It develops when the cartilage in a joint begins to wear down. As a result, the ends of your bones start to rub together when moving the joint. The joint produces more fluid to try to protect the bones, which can cause the joint to swell.
Over time, the changes in the joint can damage the bones, causing lumps called spurs to develop on the bones. This can lead to further inflammation in the tissues around the joint. OA most commonly affects the hands, hips, and knees, but it can develop in any joint. The condition causes pain, swelling, and stiffness of the affected joints.
OA can lead to trouble moving a joint and difficulties performing everyday tasks, such as walking, using stairs, washing, and dressing. OA is more common in older adults, but it can also develop in younger adults. Risk factors include aging, obesity , joint injury or surgery, and overusing a joint.
The drug works to reduce joint pain and stiffness, helping to improve the daily functioning of people with the condition. Celebrex has been widely used for OA since it was first approved in However, Celebrex is less likely to cause serious side effects than naproxen.
These side effects include heart attack , stroke , slow healing sores called ulcers , and bleeding in your digestive system. A boxed warning is the most serious warning from the FDA. RA results in inflammation in the lining of the joints. Over time, this inflammation can damage the cartilage and bone, leading to deformity of the joints. RA most commonly affects the wrists, hands, and feet, but it can affect any joint in the body. The condition always involves at least two joints and typically occurs symmetrically.
This means RA affects the same joints on each side of the body. RA can cause pain, swelling, warmth, redness, and stiffness of the affected joints. The condition can lead to trouble moving a joint and difficulties performing everyday tasks.
People with RA can also have fatigue lack of energy and feel generally unwell. Celebrex is well accepted to be effective for reducing joint pain, swelling, and stiffness in people with RA. Celebrex has been widely used for RA since it was first approved in Celebrex relieves joint pain and swelling while DMARDs help stop the immune system from attacking the joints.
These side effects include heart attack, stroke, slow healing sores called ulcers, and bleeding in your digestive system. JRA can affect one or many joints, causing pain, swelling, and stiffness. But children with this condition can also have other symptoms, such as eye inflammation , fatigue , fever , swollen glands , and a rash. The drug helps reduce joint pain and stiffness, helping to improve daily functioning in children with this condition.
AS is a type of arthritis where there is bone fusion in the spine. AS mainly affects the lower part of the spine, where it joins the pelvis. But AS can also affect parts of the body, such as the shoulders, hips, ribs, heels, hands, and feet. The condition runs in families but is more common in young men. With AS, you have inflammation in your spinal joints.
The inflammation can damage the joints and cause new bone to form. Over time, the new bone growth can fuse the vertebrae bones in your spine together. AS can cause pain and stiffness that typically starts in the lower back and buttocks. Many people with AS also have other symptoms such as fatigue , bowel inflammation , and eye inflammation. It reduces pain and stiffness, helping to improve daily functioning in people with this condition.
Celebrex is FDA-approved to treat primary dysmenorrhea period pain or menstrual cramps in adults. Dysmenorrhea can be primary or secondary. With secondary dysmenorrhea, your menstrual cramps are caused or worsened by a condition affecting your uterus or pelvic organs, such as fibroids or endometriosis. Celebrex is available as a generic drug called celecoxib.
A generic drug is an exact copy of the active drug in a brand-name medication. The generic is considered to be as safe and effective as the original drug.
Generics tend to cost less than brand-name drugs. In some cases, the brand-name drug and the generic version may come in different forms and strengths. Celebrex can cause mild or serious side effects. The following lists contain some of the key side effects that may occur while taking Celebrex. For more information on the possible side effects of Celebrex, talk with your doctor or pharmacist. They can give you tips on how to deal with any side effects that may be bothersome. Most of these side effects may go away within a few days or a couple of weeks.
Call your doctor right away if you have serious side effects. Celebrex is approved to treat juvenile rheumatoid arthritis JRA in children ages 2 years and older. The side effects of Celebrex in children are similar to those in adults. One clinical study looked at the safety of Celebrex in children with JRA who took the medication for 6 months.
In this study, the side effects reported were similar to the mild side effects reported in adults who took Celebrex. In some children, Celebrex can cause a condition called disseminated intravascular coagulation DIC. With this condition, you have abnormal blood clotting throughout your body. This is a rare form of JRA that starts with repeating fevers , often with a rash. Children with this type of JRA may need tests to check their blood clotting while they take Celebrex.
You may wonder how often certain side effects occur with this drug. As with most drugs, some people can have an allergic reaction after taking Celebrex. In clinical studies , allergic reactions occurred in 0. A more severe allergic reaction is rare but possible. Symptoms of a severe allergic reaction can include:. Call your doctor right away if you have a severe allergic reaction to Celebrex.
Some people may gain weight while taking Celebrex. In clinical studies , weight gain was reported in 0. See your doctor if you have sudden unexpected weight gain while taking Celebrex. This can be a symptom of heart failure , which is a serious side effect of Celebrex. These problems include slow healing sores called ulcers, bleeding, or perforations holes in the stomach or intestine. Older adults may also have a higher risk for kidney problems with Celebrex than younger adults.
As you age, your kidneys may not work as well. You may also need to take other medications, such as treatments for high blood pressure.
These factors can raise your risk of kidney problems. Older adults will usually start treatment with a lower dose of Celebrex mg a day to minimize the risk of side effects. Celebrex can sometimes cause a rash. In clinical studies of people with OA or RA, skin rash occurred in:. Celebrex can also make your skin more sensitive to sunlight , so you should protect your skin from the sun while taking it. Keep in mind, Celebrex can cause more serious skin reactions such as drug reaction with eosinophilia and systemic symptoms DRESS.
In some cases, these serious skin reactions can be fatal. Celebrex can sometimes cause liver problems, such as liver damage, hepatitis , and liver failure. These problems can affect how well your liver works. On rare occasions, liver problems can be fatal. These are called liver function tests.
They measure the levels of liver enzymes in your blood. Enzymes are proteins that aid chemical changes in your body. And higher levels of liver enzymes can be a sign of damage to your liver. See your doctor if you have symptoms of a liver problem while taking Celebrex. These can include:. Celebrex can sometimes cause kidney problems, such as acute kidney failure and kidney stones. In clinical studies of people who took Celebrex for OA or RA, acute kidney failure occurred in less than 0.
And kidney stones occurred in 0. You also have a higher risk if you have heart failure or liver problems, or if you become dehydrated during treatment. Dehydration can be caused by severe vomiting or diarrhea, and taking medications called diuretics water tablets.
Taking certain other medications can also increase the risk of kidney problems with Celebrex. If you have symptoms of kidney problems while taking Celebrex, tell your doctor.
Further information on the role of NSAIDs in the management of osteoarthritis is available from: Managing patients with osteoarthritis: focus on the person bpac NZ , January The inhibition of COX-2 prevents the production of the prostaglandins that mediate pain, inflammation and fever. However, as the selectivity for COX-2 inhibition increases, so does the risk of cardiovascular events.
However, as celecoxib does possess some degree of COX-1 inhibition at higher doses, the adverse effects associated with celecoxib are broadly similar to those of the non-selective NSAIDs, although their frequency may differ. See: www. Two selective COX-2 inhibitors, celecoxib Celebrex and rofecoxib Vioxx , entered the international market in and both were widely prescribed following intensive promotion focusing on their decreased risk of gastrointestinal complications.
In , the safety data on the selective COX-2 inhibitors was reviewed. Rofecoxib, however, remains unavailable as numerous studies have found that it is associated with an increased risk of cardiovascular events, relative to placebo and other NSAIDs. The clinical characteristics of the patient, their use of concurrent medicines and the pharmacology of the NSAIDs are used to determine if an NSAID is appropriate, and if so, which one should be prescribed.
The factors to consider when assessing the patient are their risk of:. All NSAIDs, including naproxen, should be used cautiously in patients with elevated cardiovascular risk. This is because all NSAIDs except aspirin are associated with a dose-dependent, increased risk of cardiovascular events that can occur in the first weeks of treatment.
This blanket caution on the use of NSAIDs with regard to cardiovascular risk is an update to previous guidance when it was advised that the use of relatively low-doses of naproxen or ibuprofen were not associated with an increased risk of cardiovascular events.
A meta-analysis of eight randomised controlled trials or prospective cohort studies compared the association between myocardial infarction, stroke and cardiovascular death and the use of eight NSAIDs, including celecoxib. A recent population-based study of more than individuals with over 61 cases of myocardial infarction found that the use of all NSAIDs was associated with an increased risk of myocardial infarction.
Celecoxib is recommended for patients at increased risk of gastrointestinal bleeding who require a NSAID. Furthermore, the COX-2 enzyme may be involved in the healing of gastric lesions and therefore celecoxib, which inhibits COX-2, may prevent previously formed gastric lesions from healing.
Patients should be advised to seek immediate medical attention if they vomit blood, pass dark stools or experience symptoms of anaemia. Patients with a high risk of gastrointestinal bleeding should be reviewed within the first month of treatment, including measurement of haemoglobin levels.
The Prospective Randomised Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen PRECISION trial found that over a mean period of 20 months there was a significantly lower risk of clinically significant gastrointestinal events or iron-deficiency anaemia of gastrointestinal origin in patients taking celecoxib 1. In patients with a history of NSAID-related gastrointestinal bleeding, the addition of a PPI to celecoxib reduces the risk of further gastrointestinal bleeding.
In patients with arthritis and a history of upper gastrointestinal bleeding, there were no cases of gastrointestinal bleeding over a month period for patients who were co-prescribed celecoxib mg, twice daily, and high-dose esomeprazole equivalent to 20 mg omeprazole, twice daily compared to 12 cases of gastrointestinal bleeding in those taking celecoxib and placebo. Prostaglandins produced by the COX enzymes influence renal function through the regulation of vascular tone and blood flow.
0コメント