DMARD tapering versus continuation in patients ≥70 years with rheumatoid arthritis in sustained low disease activity: a target trial emulation

The co-primary objective of the OASE study in patients ≥ 70 years with Rheumatoid arthritis in sustained low disease activity is to compare cs‑/b‑/tsDMARD tapering, selected according to patient preference, with continuation of therapy. Success is defined by two criteria evaluated over 24 months: • superiority in achieving ≥50 % accumulated dose reduction of conventional synthetic, biologic or targeted synthetic DMARDs; and • maintenance of equivalent disease activity, measured by the average Disease Activity Score‑28‑C‑Reactive Protein (DAS28‑CRP) within ±0.5 of baseline. Secondary objectives assess additional clinical and patient‑centred outcomes after 24 months, including: • patient‑reported outcome measures (visual analogue scale pain, fatigue, patient global, MD‑HAQ, PASS, EQ‑5D‑5L); • clinical parameters such as tender joint count, swollen joint count, C‑reactive protein, physician global assessment, remission (DAS28‑CRP < 2.6), low disease activity (DAS28‑CRP < 3.2) and ACR/EULAR Boolean 2.0 remission; • Activities of Daily Living measured by the Katz ADL scale, number of falls, clinical fragility, comorbidity index, institutionalisation, and hospitalisation rates; and • safety outcomes encompassing arthritis flare, persistent flare ≥12 weeks, non‑serious and serious infections, serious cardiovascular events, malignancy, and mortality.

The trial population comprises elderly individuals (≥70 years) diagnosed with Rheumatoid arthritis who are in sustained low disease activity (DAS28‑CRP < 3.2) for at least 12 months. Both female and male patients are eligible. Participants must have been treated with conventional synthetic, biologic, or targeted synthetic DMARDs at a stable dose for a minimum of 12 months, with no dose adjustments during that period, and may be on stable low‑dose prednisolone (≤5 mg/day) or none for at least 12 months. Additional inclusion requirements include the ability to read and understand Danish and the absence of inflammatory joint activity in the preceding year as judged by the investigator. General health status is therefore characterized by stable medication regimens, controlled disease activity, and minimal corticosteroid exposure. Lifestyle factors such as diet or physical activity are not specified as selection criteria. The sponsor did not provide the total number of participants enrolled, and the selection process was based on the outlined inclusion criteria applied to patients meeting these clinical and demographic conditions.

The OASE study is a prospective, open‑label, controlled target‑trial emulation that compares a tapering strategy for conventional synthetic, biologic, and targeted synthetic DMARDs with continuation of standard therapy in patients aged ≥ 70 years who have sustained low disease activity in rheumatoid arthritis. After an initial screening visit to confirm eligibility, participants enter a baseline visit where allocation to the tapering or control arm is recorded based on patient preference. Subsequent study visits occur at months 3, 6, 12, 18 and 24, during which medication dosing, disease activity (DAS28‑CRP), safety parameters, and adherence are assessed; an end‑of‑study visit at month 24 finalises data collection for the primary endpoint. The total involvement for each participant is approximately 24 months, with an optional follow‑up assessment at year 5 for secondary outcomes. Early termination may occur if a participant experiences a disease flare requiring re‑initiation of full DMARD dosing, develops a serious adverse event related to study medication, or withdraws consent. The primary co‑primary endpoints are (A) the proportion of accumulated DMARD dose reduction over 24 months and (B) maintenance of equivalent disease activity, defined by an average DAS28‑CRP within ±0.5 of baseline throughout the observation period.

rheumatoid arthritis patients in the study may receive Jyseleca 200 mg film‑coated tablets containing filgotinib, administered orally at a dose of 200 mg per tablet, typically once daily.

Olumiant 4 mg film‑coated tablets, containing baricitinib, are administered orally at a dose of 4 mg per tablet, usually once daily.

Infliximab is provided as a solution for infusion with a dose of 12.5 mg per infusion; administration is performed intravenously according to the study infusion schedule.

Certolizumab pegol is supplied as a solution for injection at a dose of 14.29 mg per injection; subcutaneous administration follows the protocol‑defined timing.

Hydroxychloroquine sulfate is given as oral tablets at a dose of 400 mg per tablet, generally taken once daily.

Rinvoq 15 mg prolonged‑release tablets contain upadacitinib and are taken orally at a dose of 15 mg once daily.

Adalimumab is provided as a solution for injection at a dose of 2.86 mg per injection; subcutaneous dosing follows the study schedule.

Sulfasalazine is administered orally as a powder for capsules at a dose of 3 g per day, divided as appropriate.

Sarilumab is supplied as a solution for injection with a dose of 14.3 mg per injection; subcutaneous administration follows the predefined intervals.

RoActemra (tocilizumab) 162 mg solution for injection in a pre‑filled syringe is given intravenously at a dose of 23.14 mg per infusion, according to the protocol schedule.

Methotrexate sodium is available both as a solution for injection and as oral tablets, each at a dose of 3.6 mg per administration; the route (intravenous or oral) is assigned per protocol.

Golimumab is provided as a solution for injection at a dose of 1.67 mg per injection; subcutaneous dosing follows the study timetable.

Orencia (abatacept) 250 mg powder for concentrate for solution for infusion is reconstituted and administered intravenously at a dose of 35.71 mg per infusion.

Prednisolone 5 mg soluble tablets are taken orally at a dose of 5 mg per tablet, typically once daily.

Xeljanz 5 mg film‑coated tablets (tofacitinib) are administered orally at a dose of 10 mg per tablet, usually divided into two daily doses.

Leflunomide is given orally at a dose of 20 mg per tablet, taken once daily.

Etanercept is supplied as a solution for injection at a dose of 7.14 mg per injection; subcutaneous administration follows the protocol‑specified frequency.

RoActemra (tocilizumab) 20 mg/mL concentrate for solution for infusion is administered intravenously at a dose of 28.57 mg per infusion according to the study schedule.

Orencia (abatacept) 125 mg solution for injection in a pre‑filled syringe is given intravenously at a dose of 17.9 mg per infusion, following the protocol timing.

Compliance with oral regimens is monitored by pill counts and patient diaries, while infusion and injection adherence is documented through infusion logs and electronic case report forms.

Efficacy will be assessed by two co‑primary parameters. The first parameter is the accumulated DMARD dose reduction, calculated as the mean percentage reduction across conventional synthetic, biologic, and targeted synthetic DMARDs relative to baseline dosing over the 24‑month observation period. Dose reductions for each DMARD class are expressed as a percentage of the initial prescribed dose, and the overall reduction is derived by averaging these percentages.

The second parameter is disease activity, evaluated using the average DAS28‑CRP score across the 24‑month period. DAS28‑CRP will be obtained at scheduled study visits using the validated composite score that incorporates tender and swollen joint counts, patient‑reported global health assessment, and serum C‑reactive protein concentration. The mean DAS28‑CRP value for each participant will be calculated, and equivalence between the tapering and control groups will be declared if the difference in mean scores lies within the predefined margins of ±0.5.