Selective COX-2 inhibitors significantly reduce the occurrence of heterotopic ossification after hip arthroscopic surgery

A well known complication after hip arthroscopic surgery is heterotopic ossification (HO), the presence of bone in soft tissue. This complication can be as prevalent as 44% of patients when no prophylactic intervention is given. Although it is not totally understood how HO occurs, it is known that mesenchymal cells provide the origin for this, and they are activated by inflammatory mediated response in injured tissues. Low-dose irradiation and nonsteroidal anti-inflammatory drugs are the two most commonly used interventions for this problem of reducing and preventing HO. This study hypothesized that postoperative HO prophylaxis using 600 mg of etodolac once daily for two weeks would significantly reduce risk of HO in patients after surgery in comparison with a groups of patients who were treated by the same surgeon who did not receive NSAID prophylaxis. Their ultimate goal of the study was to evaluate the effectiveness of short-term selective COX-2 inhibitors (specific NSAID) when they are being used prophylactically for HO.

In this retrospective analysis of data gathered from a cohort of patients who underwent surgery by the same surgeon for the same reason, femoroacetabular impingement.  Although the study started out with 263 patients patients, 163 were included in the final analysis because 100 of them had to be excluded for various reasons including lost to follow-up, previous hip surgery or HO, and not meeting inclusion criteria. 100 patients were assigned to the control group and 63 were included in the group that received COX-2 inhibitor prophylaxis. In the control group, 35 of 100 patients developed HO. The patients were tested for HO 2 weeks, 6 months, and 1 year after surgery. The data did exhibit a significant difference between the control and study groups, as there were no patients in the study group who developed HO. This is the first study to ever look at a dose this low, half of the maximum, in attempting to prevent HO with this specific medication. It is significant that this research is able to show a short-term, selective NSAID can be used to effectively prevent HO in this patient population because it gives the patients much less of a risk of developing the GI side effects that are so closely associated with traditional NSAIDs.

It is interesting how choosing between medications in the same class can often be very significant when treating a patient and trying to keep them as healthy and happy as possible. In what other classes of drugs can this be significant?
Rath E, Warschawski Y, Maman E, et al. Selective COX-2 inhibitors significantly reduce the occurrence of heterotopic ossification after hip arthroscopic surgery. Sports Med. 2016;44:677-81.

Synthesis of dihydropyrazole sulphonamide derivatives that act as anti-cancer agents through COX-2 inhibition

For years now, COX-2 inhibitors have been used to treat pain and inflammation. Recently, much research has suggested that they may potentially be able to reduce tumour processes. COX-2 can be upregulated by tumor promotors, revealing that it may be involved in pathological processes of various types of cancer. Currently, there are hundreds of clinical trials being conduced testing the anti-tumor properties of COX-2 inhibitors such as celecoxib.

The investigators in this study created new COX-2 inhibitors derived from an analysis of currently known COX-2 inhibitors. One of the dihydropyrazole sulphonamide derivatives developed, 4d, demonstrated high COX-2 selectivity and anticancer properties. Further, it was shown that 4d could stop the cell cycle at the G2/M phase. It also induced apoptosis in A549 (tumor cell-line) cells. Overall, it seems that compound 4d could potentially be utilized for cancer treatment.

Qiu H, Wang P, Zhen L, et al. Synthesis of dihydropyrazole sulphonamide derivatives that act as anti-cancer agents through COX-2 inhibition. Pharmacol Res. 2016;104:86-96.

 

Does celecoxib improve the efficacy of chemotherapy for advanced non-small cell lung cancer?

Lung cancer is the most common culprit of cancer-related death globally. Currently, treatment for this type of cancer can only help patients so much.  The American Cancer Society estimates that 158,080 patients will die from lung cancer in 2016.  Thus, looking for new forms of treatment is a crucial focus of current research.  This study, knowing of a newfound relationship between cancer and inflammation, decided to look into the efficacy of celecoxib, as COX-2 inhibitor, as an add-on therapy to current chemotherapeutics.  This study was a meta-analysis of previous clinical trials that were on their own somewhat inconsistent.

The researchers performed a literature search and analyzed data from all published randomized controlled trials that had studied celecoxib as adjunct treatment to chemotherapy in patients with non-small cell lung carcinoma.  Eventually they narrowed the group of 206 such studies down to six trials that met their criteria for closer review.  The investigational treatment was celecoxib plus chemotherapy, and chemotherapy alone served as the control.  They looked at toxicity and efficacy, and determined that improved efficacy of the group with added-on celecoxib therapy was statistically significant.  Although they found an increased overall response rate with celecoxib, they could not determine how it affected overall survival due to lack of data.  They call for further randomized clinical trials to better determine the best treatment course.

I think that completion of meta-analyses such as this one are important because it sums up what different researchers have found recently in regards to one specific problem, and can then use that condensed information to direct future research on the topic.  For example, researchers trying to determine whether it is worth it to study celecoxib and chemotherapy treatment further can look to this review article and see that it is an area that has potential as a solution, as well as room for new data.  What are your thoughts on how meta-analyses play into future research studies?

 

Hou LCHuang F, Xu HB.  Does celecoxib improve the efficacy of chemotherapy for advanced non-small cell lung cancer?.  Br J Clin Pharmacy. 2016;81:2332.

http://onlinelibrary.wiley.com/doi/10.1111/bcp.12757/full