Op0261 Assessment of the Remission Maintenance After Tocilizumab Withdrawal in Polymyalgia Rheumatica Patients Receiving a 6-Month Treatment

Background: The SEMAPHORE trial1 was a randomized controlled prospective study to assess the safety and efficacy (success defined by PMR-AS≤10 and GC≤5mg or GC decrease ≥10mg/day) of intra venous (i.v.) tocilizumab (TCZ) in glucocorticoids (GC)-dependent polymyalgia rheumatica (PMR). Tocilizumab was shown to reduce GC while improving clinical and biological inflammatory parameters at 24 weeks. After the 24-week study, patients entered a double-blind extension. Objectives: In this study, we aimed to assess after the 24th week the relapse rate and markers of patients who received a 6-month TCZ treatment and achieved remission. Methods: Among 101 patients randomly 1:1 allocated to receive i.v. 8mg/kg TCZ or placebo for 24 weeks in the SEMAPHORE trial, 49 received TCZ and 33 of them succeed (Figure 1). All 33 patients but one stopped TCZ at week 24 and they visited at week 32, with optional follow-up visits every 8 weeks until week 48. The relapse was defined by the failure of the primary composite outcome during follow-up or the need for ≥1 TCZ infusion. Results are presented by proportion of patients achieving success at each visit and the outcome over time using a Kaplan Meier curve. Results: Among the 33 TCZ group patients in remission at week 24, 7 stopped follow-up before the 48th week, 5 of the other 26 subjects (19.2%) sustained remission in the 6 following months, 21 (80.8%) relapsed. Median time to relapse was 15 weeks (interquartile range: 8-25). 15 patients were considered in relapse because of PMR-AS≥10, 4 for isolated CRP elevation, 2 after the clinician's decision. Among the 16 patients treated with TCZ but not in remission at 24th week, 4 of them (25%) achieved the primary outcome after continuing TCZ for 24 other weeks. Conclusion: Among patients with GC-dependent PMR, in remission after a 6-month TCZ treatment, only a quarter remained relapse-free after treatment discontinuation. This study suggests that a 6-month treatment is not enough to withdraw TCZ. Further studies assessing the required duration of anti-IL6-receptor treatment to limit PMR relapses are needed. REFERENCES: 1 Devauchelle-Pensec, V. et al. Effect of tocilizumab on Disease Activity in patients with active polymyalgia rheumatica receiving glucocorticoid therapy: A Randomized Clinical Trial. JAMA 328, 1053–1062 (2022). Acknowledgements: We thank the French rheumatologists, particularly those from the French University Hospital VICTOR HUGO (InnoVation en reCherche OsTeo-aRticulaire des Hôpitaux Universitaires du Grand Ouest) network (srouest.fr), and the general practitioners who referred their patients to this trial. We are grateful to the Clinical Investigations Center (CIC) 1412, Institut National de la Santé et de la Recherche Médicale (INSERM), Brest, France, for centralizing the trial data and to Audrey le Goff, MS; Adrien Clarysse, MS; and Valentine Guiton, MS, of the Brest University Hospital research board (DRCI) at the Brest University Hospital, who received no compensation for their role in the study. Disclosure of Interests: Baptiste Chevet Galapagos, I wrote congress review for a journal they own, I received support outside of this work from Amgen, Abbviie, Novartis, Santi, Sandoz, Souki Aghiles: None declared, Nowak Emmanuel Dr Nowak reported receiving nonfinancial support from Roche-Chugai Pharmaceutical, which donated the infusion form of tocilizumab during the conduct of the study., Dr Nowak reported receiving grants from the French National Program for Clinical Research, Guillermo Carvajal Alegria Dr Carvajal Alegria reported receiving personal fees from Chugai Pharmaceutical outside the submitted work., Emmanuelle Dernis Dr Dernis reported receiving personal fees from Novartis, Bristol Myers Squibb, UCB, AbbVie, Nordic Pharma, Amgen, and Janssen outside the submitted work., Christophe Richez Dr Richez reported receiving personal fees from Sanofi, personal fees from Lilly, and personal fees from Novartis outside the submitted work., Marie-Elise Truchetet: None declared, Daniel Wendling Dr Wendling reported personal fees from AbbVie, Bristol Myers Squibb, MSD, Pfizer, Chugai Pharmaceutical, Amgen, Nordic Pharma, UCB, Novartis, Janssen, Eli Lilly, Grunenthal, and Galapagos outside the submitted work, Eric Toussirot: None declared, Aleth Perdriger: None declared, Jacques-Eric Gottenberg Dr Gottenberg reported receiving personal fees from Roche-Chugai Pharmaceutical, Sanofi, Pfizer, Eli Lilly, Gilead, and Abbvie and grants from Bristol Myers Squibb outside the submitted work., Renaud Felten: None declared, Bruno Fautrel Dr Fautrel reported receiving personal fees from Roche Chugai Pharmaceutical during the conduct of the study., Anne Lohse: None declared, Laurent Chiche: None declared, Pascal Hilliquin: None declared, Catherine Le Henaff Bourhis: None declared, Dervieux Benjamin: None declared, Guillaume Direz Dr Direz reported receiving personal fees from Novartis and personal fees from Roche-Chugai Pharmaceutical outside the submitted work., Isabelle Chary-Valckenaere: None declared, Divi Cornec: None declared, Dewi Guellec: None declared, Thierry Marhadour: None declared, Alain Saraux Dr Saraux reported receiving grants from Roche-Chugai Pharmaceutical and grants from the French National Program for Clinical Research during the conduct of the study and personal fees from Nordic Galapagos, AbbVie, Eli Lilly, Nordic, and Roche-Chugai and grants from Eli Lilly outside the submitted work., Valerie Devauchelle-Pensec Dr Devauchelle reported receiving personal fees from Chugai Pharmaceutical and AbbVie a, Dr Devauchelle-Pensec reported grants and personal fees from Novartis during the conduct of the study and personal fees from Galapagos, Pfizer, Bristol Myers Squibb, Janssen, and AbbVie outside the submitted work.