OP0098 Assessing the Frequency of Difficult-to-Manage (D2M) and Treatment-Refractory (TR-axSpA) Cases in the RABBIT-SpA Register: An Analysis Based on Recent ASAS Definitions

Background: Despite advances in therapeutic strategies, a subset of axSpA patients continues to experience persistent disease activity or inadequate response to treatment, underscoring the need to better characterize these challenging cases. Recent criteria proposed by the Assessment of SpondyloArthritis International Society (ASAS) define two clinically relevant subgroups within axSpA and inadequate treatment response: Difficult-to-Manage (D2M-) and treatment-refractory (TR-) axSpA [1]. Objectives: This analysis aimed to determine the frequency of axSpA patients meeting the recently proposed D2M- and TR-axSpA criteria as well as to describe patient characteristics at the time point of initiating the first b/tsDMARD treatment. Methods: Utilizing data from RABBIT-SpA, a German prospective longitudinal register, this analysis included b/tsDMARD-naïve axSpA patients initiating b/tsDMARD therapies, with at least 12 months of follow-up. The analysis applied the new ASAS criteria to identify D2M-axSpA and TR-axSpA cases. To qualify for inclusion in the D2M group from our preselected cohort, patients must meet the first criterion of the D2M definition, which requires that a patient must have experienced treatment failure of ≥2 b/tsDMARDs with different modes of action. To evaluate insufficient control of signs and symptoms – the second component of the D2M definition – the following criteria were assessed: high disease activity: ASDAS ≥2.1; signs and symptoms suggestive of active disease: arthritis joint count ≥1, enthesitis ≥1, BASDAI question-2 (axial involvement) ≥4, new onset of uveitis, psoriasis, or inflammatory bowel disease; CRP ≥5 mg/L; active inflammation on MRI of the sacroiliac joints (SIJ) and/or spine or patient global assessment (PtGA) ≥4. The third D2M criterion was fulfilled if either the physician global assessment (PhGA) or PtGA was ≥4. Treatment refractory (TR-axSpA) status was defined as patients meeting the D2M criteria with explicit evidence of high disease activity (ASDAS ≥2.1) AND either active inflammation on MRI of the SIJ/spine OR an elevated CRP (≥5 mg/L). Results: From 1850 patients, 881 (48%) were b/tsDMARD-naïve at inclusion in the RABBIT-SpA registry and met the predefined follow-up. Among them, 137 (16%) patients underwent treatment with at least two different modes of action. Seventy-five patients (8.5% of the 881 selected pts.) met the ASAS criteria for D2M axSpA (Figure 1). D2M patients were predominantly females, with a lower education level, they were less likely to be HLA-B27 positive and displayed more frequent clinical signs of enthesitis and arthritis but fewer objective signs such as MRI-detected inflammation in the spine or elevated CRP levels. All patient reported outcomes (PRO) were worse in this group. Twenty-two of these (2.5% of the 881 selected pts.) also met the TR criteria, characterized by persistent active disease and objective signs of inflammation. This specific subgroup also showed higher rates of elevated CRP levels and SIJ/spinal inflammation on MRI at baseline. Additionally, they had a lower likelihood of being HLA-B27 positive and were more frequently smokers (Table 1). Conclusion: Approximately 8.5% of b/tsDMARD-naïve axSpA patients met the D2M criteria, and 2.5% qualified as TR. D2M-axSpA patients were more often female and less likely to be HLA-B27 positive, when compared to those patients not fulfilling these definitions. Furthermore, D2M-axSpA was associated with higher peripheral involvement and worse PROs at initiation of their first b/tsDMARD treatment. REFERENCES: [1] Poddubnyy D. et al.; The Assessment of SpondyloArthritis International Society (ASAS) Definition of Difficult-to-Manage Axial Spondyloarthritis [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). Figure 1Flow Chart of Patient Selection Table 1Baseline characteristics of b/tsDMARDs naive axSpA patients with at least 12 months follow up time in RABBIT-SpA.b/tsDMARD naive axSpA patientsn=881nD2M/nTRn=806D2Mn=75→TRn=22Gender (Female)n (%)339 (42.1)40 (53.3)9 (40.9)AgeMean (SD)42.4 (13)45 (12)42.7 (12.6)Symptom duration (years)Mean (SD)10.7 (10.8)11.1 (9.9)10.6 (8.5)Smoking (yes)n (%)282 (39.3)28 (42.4)8 (50)Years of education (≥ 10 years)n (%)581 (80.6)47 (71.2)14 (82.4)Enthesitis (current)n (%)138 (17.2)20 (26.7)6 (27.3)Arthritis (current)n (%)219 (27.3)25 (33.3)5 (22.7)HLA-B27 (positive)n (%)608 (77.2)49 (68.1)12 (54.5)PhGA (NRS 0-10)Mean (SD)5.7 (1.7)6.3 (1.6)6.2 (1.6)PtGA (NRS 0-10)Mean (SD)5.8 (2.4)6.8 (1.7)6.8 (1.3)BASDAI (NRS 0-10)Mean (SD)4.6 (1.9)5.3 (1.8)5.1 (2)BASFI (NRS 0-10)Mean (SD)3.7 (2.3)4.3 (2.2)3.7 (1.9)ASDASMean (SD)2.9 (1)2.9 (0.6)3.1 (0.8)CRP (positive, ≥ 5mg/L)n (%)434 (57.7)36 (50)16 (72.7)Active inflammation MRI SIJ (yes)n (%)482 (80.3)40 (80)10 (83.3)Active inflammation MRI spine (yes)n (%)252 (57.8)24 (51.1)9 (64.3)Comorbidities (≥ 3)n (%)115 (14.3)12 (16)3 (13.6)Depression (yes)n (%)36 (4.5)5 (6.7)1 (4.5)WHO5 (moderate/severe)n (%)194 (27.1)24 (36.4)9 (52.9) Acknowledgements: RABBIT-SpA is supported by a joint, unconditional grant from AbbVie, Amgen, Biocon Biologics, Biogen, Celltrion, Janssen-Cilag, Lilly, Novartis, Pfizer, and UCB. We thank all participating patients and rheumatologists. Disclosure of Interests: Fabian Proft Speakers bureau with payments made directly to me for: AbbVie, AMGEN, BMS, Celgene, Eli Lilly, Hexal, Janssen, Medscape, MSD, Novartis, Pfizer, Roche and UCB, Consultancy with payments made directly to me for: AbbVie, BMS, Janssen, Novartis, Pfizer and UCB, Grant/research support from Novartis, Eli Lilly and UCB with payments made via my institution, Stephanie Lembke: None declared, Anja Weiß: None declared, Herbert L Kellner: None declared, Xenofon Baraliakos Research Grants, Consultant, Scientific Advisory Board: Abbvie, Alphasigma, Amgen, BMS, Cesas, Celltrion, Galapagos, Janssen, Lilly, Moonlake, Novartis, Pfizer, Roche, Sandoz, Springer, Stada, Takeda, UCB, Zuellig; Funding: Abbvie, Janssen, Novartis, Celltrion, See above, See above, Denis Poddubnyy speaker fees from AbbVie, Canon, DKSH, Eli Lilly, Janssen, MSD, Medscape, Novartis, Peervoice, Pfizer, and UCB, consulting fees from AbbVie, Biocad, Bristol-Myers Squibb, Eli Lilly, Janssen, Moonlake, Novartis, Pfizer, and UCB, received research support from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Anne Regierer Amgen, BMS, Novartis, Pfizer, Roche, none personal. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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