LAUSR

Combined biological therapy (CBT) is discouraged in the treatment guidelines of immunemediated diseases due to lack of consistent evidence. The blockade of two inflammatory pathways together could increase the overall risk of infections or unexpected adverse events (AEs). Nevertheless, several reports have shown beneficial results of CBT in refractory patients with inflammatory bowel disease (IBD), with a low rate of serious AE. 2 Combination treatments most used include an antitumour necrosis factor (TNF) or antiIL12/23 receptor (antiIL12/23R) antibody plus an anti-α4/β7integrin agent. In psoriatic arthritis (PsA), previous case series have shown favourable efficacy results with CBT, mainly with an antiTNF agent in combination with an antiIL12/23R, 4 but some patients presented AE. 4 The experience with CBT in spondyloarthritis (SpA) is limited, usually in patients with concomitant IBD. 2 The aim of this work was to determine the effectiveness and safety of CBT in patients with SpA. We present a retrospective case series, which identified nine patients with SpA under CBT, from April 2017 to October 2021, with a minimum 3month exposure to two simultaneous biologics with different therapeutic targets (table 1). All patients fulfilled criteria for axial or peripheral SpA according to ASAS criteria and provided a written informed consent. Demographics, clinical, laboratory and safety data were collected from electronic health records. Cutoff values for a major clinical improvement were a change in Ankylosing Spondylitis Disease Activity ScoreC Reactive Protein (ASDASCRP) >2 units and in DAS28CRP >1.2, whereas remission was defined as ASDASCRP <1.3 or DAS28CRP <2.6 for axial or peripheral disease, respectively. Prior to CBT start, all patients showed high disease activity with several domain involvement and a mean disease duration of 20.9±11.3 years. Mean number of previous biologic/targeted drugs was 4.7±1.3. Six patients received dual antiTNF and antiIL17A blockade. Three patients, with concomitant Crohn disease, were prescribed an antiTNF combined with either IL12/23R, IL23R or α4/β7integrin antagonists. Eight patients had previously used separately, either the combined drugs (5/9) or agents directed to previously used targets (3/9). Just in case 8, an agent directed to a new target (IL23R) was added to a previous antiTNF (additional information in online supplemental material). Median exposure to CBT was 14.8 (IQR: 8–19.5) months. Most patients achieved major clinical improvement and 4/9 achieved remission, allowing for stepping down of initial dose in some patients (online supplemental table S1). Only one patient experienced a transient uveitis relapse. Interestingly, no unexpected AEs were identified and just one serious infection was recorded, not clearly attributable to CBT. A Staphylococcus aureus bacteremia occurred in a 60yearold woman with multiple comorbidities who was admitted for liver decompensation, and CBT was finally discontinued. At last evaluation, seven patients still maintain CBT with favourable results and one patient under 3month followup has not experienced any improvement yet. In our case series, 8/9 cases achieved major clinical improvement, irrespective of whether the combination used previously tested drugs/targets or a new target was added to the CBT. Those findings suggest that dual inhibition could be superior to individual target monotherapies, without significant safety concerns. Preclinical studies in animal models with dual TNF/IL17 blockade propose a synergistic effect. Furthermore, our data are similar to those described in IBD studies with dual use of antiTNF drugs and antiIL12/23R or anti-α4/β7integrin agents, 2 but no data on the association between antiTNF and Letter