Dutch rheumatologists have started a clinical study in patients with difficult-to-treat rheumatoid arthritis (RA). They compare the efficacy of adding either tocilizumab or prednisone in patients who do not benefit sufficiently from treatment with the conventional RA drug methotrexate.

Patients with RA are usually first treated with a conventional RA drug such as methotrexate. If such treatment has insufficient effect, there are several drugs that can be added to the starting medication. However, it is not known which of these drugs is most effective and therefore there exists no standard treatment for patients in whom a conventional starting drug is insufficiently effective. In the TOPIRA study, which will include 120 RA patients, investigators will compare the efficacy of two RA drugs (prednisone and tocilizumab) that are used in clinical practice in treatment resistant patients. This well-controlled study, which will last for at least 12 months, is being conducted in four Dutch healthcare institutions and is led by Prof. Dr. Jaap van Laar (Department of Rheumatology and Clinical Immunology, UMC Utrecht).

Best treatment

Tocilizumab (costs € 10,000 per year) is a biological that targets the inflammatory protein interleukin 6 (IL-6). IL-6 is produced by inflammatory processes and maintains inflammation. It is given weekly by subcutaneous injection. Prednisone (costs € 40 per year) is a drug with a broad anti-inflammatory activity that inhibits the inflammatory symptoms of all kinds of diseases, including RA, and is given daily as an oral tablet.

Both drugs can reduce joint inflammation and limit joint damage, but both can also cause side effects. It is unknown whether tocilizumab is more effective than prednisone for suppressing RA. It is also unknown whether fewer side effects occur than with prednisone. After this study, the researchers hope to know better which treatment works best in RA patients who do not respond sufficiently to a conventional starting treatment with methotrexate.

Cost

Principal investigator Jaap van Laar on the importance of this study: “When this study demonstrates that the profile of prednisone is comparable to that of tocilizumab, this can result in enormous cost savings given the large price difference. However, if tocilizumab were to work significantly better than prednisone, this may - despite the higher costs - justify the use of tocilizumab in this patient population”.

For the TOPIRA study, pharmaceutical company Roche (producer of tocilizumab) has made € 1 million available (the company has no further influence on the implementation, analysis and publication of the study). Hospitals participating in the study are UMC Utrecht, Meander Medical Center in Amersfoort, Medical Center Leeuwarden and Reumazorg ZuidWest Nederland.

Participants wanted

Participants are still being sought for the TOPIRA study. Potential participants must meet the following conditions:

• Have used at least two conventional RA drugs or at least one conventional RA drug in combination with unfavorable prognostic factors;
• Current use at least one conventional RA drug;
• The conventional RA must have been used at a stable dose for at least 8 weeks;
• Be at least 18 years old and have a sufficient command of the Dutch language.
• Have painful and swollen joints.
• Have not used any other biological or JAK inhibitor in the past. A maximum of 1 TNF inhibitor is allowed.

More information about the TOPIRA study for potential participants can be found on the special study page on the UMC Utrecht website.