Comparison of gastrointestinal safety and tolerability of aceclofenac with diclofenac: a multicenter, randomized, double-blind study in patients with knee osteoarthritis

Abstract

Objective:

To compare the gastrointestinal (GI) tolerability and efficacy of aceclofenac with diclofenac in patients with knee osteoarthritis (OA).

Methods:

In this randomized, double-blind, double-dummy, multicentric, comparative study, post 7 day placebo washout, patients were randomly allocated to receive either aceclofenac 100 mg b.i.d. or diclofenac 50 mg t.i.d. and were followed up for the next 6 weeks. The GI tolerability was evaluated based on the incidence and severity of predefined GI adverse events (AEs), number of gastroprotective agents (GPAs) consumed by patients, and discontinuation from the study due to GI AEs. The secondary outcome included assessment of pain intensity using a visual analogue scale (VAS), Western Ontario and McMaster Universities (WOMAC) score, pain relief score, and investigators’ and patients’ overall assessments of response to study drugs.

Results:

A total of 591 (aceclofenac group: 297; diclofenac group: 294) patients were enrolled. The cumulative incidence of GI AEs for dyspepsia (28.1% versus 37.9%; p = 0.014), abdominal pain (19% versus 26.3%; p = 0.037), overall incidence of predefined GI AEs (57.3% versus 73.6%; p < 0.001) and number of patients reporting GI AEs (28.9% versus 36.5%; p = 0.053) were significantly less in the aceclofenac group compared to the diclofenac group throughout the study. All the AEs were mild to moderate in intensity. Fewer patients from the aceclofenac group required GPAs compared to the diclofenac group (28.17% versus 33.68%; p = 0.155). During first 7 days of therapy, >90% of patients from aceclofenac group did not require GPAs. There were no differences between the study groups in the various pain assessment scales when measured during the study period.

Conclusion:

Aceclofenac was better tolerated in terms of incidence and severity of GI AEs and GPA requirement and was as efficacious as diclofenac. The need for GPAs increased with the increase in duration of treatment with NSAIDs. Hence, it could be concluded that usual practice of co-prescription of GPAs with aceclofenac could be avoided to improve patient compliance and reduce cost of treatment. However, long term trials with endoscopic evaluation in the wider population are required to assess the GI tolerability of aceclofenac and diclofenac in detail.

Keywords::

• Aceclofenac
• Diclofenac
• Gastrointestinal tolerability
• Knee osteoarthritis
• NSAIDs

Transparency

Declaration of funding

This study was sponsored by Ipca Laboratories Ltd, Mumbai, India.

Declaration of financial/other relationships

A.P. and N.C. have disclosed that they are employees of Ipca Laboratories Ltd, and were involved in the conceptualization, coordination and execution of the study at all centers. All the study investigators received funding from Ipca Laboratories Ltd, India.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

The authors thank Ravikiran Payghan, Shruti Kulkarni, Vivek Raut, Surendra Pandia, Tushar Jadhao, and Neha Magar, who are employees of Ipca Laboratories Ltd, for their technical support in coordinating the study-related activities at all the sites, Kumar Naidu and Avinash Mule, employees of Ipca Laboratories Ltd, for statistical analysis and data management for this study, and Pankaj Wadibhasme, employee of Ipca Laboratories Ltd, for providing necessary drafting assistance for this manuscript.

The authors also thank and recognize the contribution of the all study investigators: Dr. Yatin Desai, Sheth Vadilal Sarabhai General Hospital and Sheth Chinai Maternity Hospital, Ahmedabad, India. Dr. Hiranya Kumar S, Vydehi Institute of Medical Sciences and Research Centre, Bangalore, India. Dr. Anil Kumar Gupta, Mahatma Gandhi Medical College and Hospital, Jaipur, India. Dr. R.P.S. Boparai, Government Medical College, Amritsar, India. Dr. Suresh Korlhalli, Karnataka Institute of Medical Science, Hubli, India. Dr. G.N. Pundkar, Dr. Panjabrao Deshmukh Memorial Medical College, Amravati, India. Dr. N.S. Dhaniwala, Swami Ramanand Teerth Rural Medical College, Ambajogai, India. Dr. B. Udaya Kumar, King George Hospital, Visakhapatnam, India. Dr. M.K. Ravindran, Calicut Medical College, Calicut, India. Dr. Nirmal Jain, National Institute of Medical Sciences, Jaipur, India. Dr. R.N. Daveshwar, Medical College and Sir Sayajirao General Hospital, Vadodara, India. Dr. Rajesh Solanki, Civil Hospital, Ahmedabad, India. Dr. Sunil Shah, Civil Hospital, Nasik, India. Dr. Kaladagi P.S., Mysore Medical College, Mysore, India. Dr. Sushil Mankar, Lata Mangeshkar Hospital, Nagpur, India. Dr. C.R. Thorat, Government Medical College, Aurangabad, India. Dr. T. Venkateshwar Rao, Mahatma Gandhi Memorial Hospital, Warangal, India. Dr. Prashant Kamath, Maharashtra Institute of Medical Education and Research, Pune, India. Dr. Edward Nazareth, Father Muller Medical College Hospital, Mangalore, India. Dr. Arun Kumar Rao, Maharashtra Institute of Medical Sciences and Research, Latur, India. Dr. Rahul Bade, Government Medical College, Kolhapur, India.

The authors would also like to thank Dr. Ritesh Chotaliya, Dr. Manoj Kumar Shukla, Dr. Lohit B. M., Dr. Mahesh Goyal, Dr. Sandeep Naik, Dr. Arshad Patel, Dr. Deepak Lamture, Dr. Manan Chaya, Dr. Mukesh Tiwari, Dr. Anand Tailor, Dr. Dinesh Patil, Dr. Vinayak, Dr. M. Faizan, Dr. Vishnu Palve, and Dr. Katam Ramkumar Reddy who were the study co-investigators at study centers.