Better results with rhenium-186 radiosynoviorthesis than with cortivazol in rheumatoid arthritis (RA): A two-year follow-up randomized controlled multicentre study

J.G. Tebib¹, L.M. Manil⁵, G. Mödder⁶, P. Verrier³, Y. De Rycke⁵, A. Bonmartin⁴, J.-Y. Devaux⁴, F. Chossat⁵, C.J. Menkes³, A. Kahan³

¹Department of Rheumatology and ²Department of Nuclear Medicine, Centre Hospitalier Lyon-Sud; ³Department of Rheumatology and ⁴Department of Nuclear Medicine, University of Paris 5 and Cochin Hospital, Paris; ⁵Schering-CIS Bio International, Gif-sur-Yvette, France; ⁶Department of Nuclear Medicine, University of Köln-Marsdorf, Germany

ABSTRACT
Objective
The aim of this international multicentric randomized phase 3 clinical trial was to compare prospectively radiosynoviorthesis (RSO) with rhenium-186-sulfide (¹⁸⁶Re) to intra-articular corticotherapy in patients with clinically controlled rheumatoid arthritis (RA), but in whom one or a few medium-sized joints remained painful or swollen. 

Methods
One hundred and twenty-nine joints in 81 RA patients [stratified into 2 groups: wrists (group 1, n = 78) and all the other joints (group 2, n = 51, including 18 elbows, 21 shoulders and 12 ankles)] were randomized to receive intra-articular injections of either ¹⁸⁶Re-sulfide (64 ± 4 MBq), or cortivazol (Altim®) 3.75 mg. Clinical assessment was performed before and then at 3, 6, 12, 18 and 24 months after local therapy, using a 4-step verbal rating scale (VRS) and a 100 mm visual analog scale for pain, a 4-step VRS for joint swelling and mobility and a 2-step VRS for the radiological stage. The Mantel-Haenszel test was used for qualitative variables, analysis of variance (ANOVA) for quantitative pain analysis and Kaplan-Meyer survival test for relapse analysis.

Results
¹⁸⁶Re was observed to be statistically superior to cortivazol at 18 and 24 months while no statistical difference was seen for any criterion at 3, 6 and 12 months post injection. At 24 months, the difference in favor of ¹⁸⁶Re was significant for pain (p = 0.024), joint swelling (p = 0.01), mobility (p = 0.05, non-wrists only), pain and swelling (p = 0.03) and pain or swelling (p = 0.02). "Survival" studies (Kaplan-Meyer) demonstrated a greater relative risk of relapse in corticoid treated joints, but only from the second year of follow-up. No serious side effect was observed in any patient, with only light and transient local pain and/or swelling occurring in 24% of cases, regardless of the treatment used. 

Conclusion
¹⁸⁶Re -sulfide and cortivazol had similar efficacy up to 12 months post-injection, but ¹⁸⁶Re became clearly more effective at 18 and 24 months, for all criteria monitored and for RA outcome. Therefore, ¹⁸⁶Re RSO can be recommended for routine clinical use.

Key words
Radiosynoviorthesis, Rhenium-186, rheumatoid arthritis, corticosteroid, intra-articular.

Please address correspondence to: Prof. Jacques G. Tebib, MD, Department of Rheumatology, Centre Hospitalier Lyon-Sud, 69310 Pierre Benite, France.

Clin Exp Rheumatol 2004; 22: 609-616.
© Copyright Clinical and Experimental Rheumatology 2004.