Influence of Methotrexate Discontinuation on Immunogenicity After PCV-20 Vaccine in Patients ARDs

Proportion of participants who achieve seroconversion, defined as at least a twofold increase in IgG antibody concentrations for ≥50% of PCV20 vaccine serotypes (1, 3, 4, 5, 6B, 7F, 8, 9V, 12F, 14, 19A e 23F) compared to baseline, measured by multiplex Luminex assay.

Functional antibody response will be assessed according to the serotype-specific opsonophagocytic activity (OPA), defined as at least a twofold increase in IgG antibody concentrations for ≥50% of vaccine serotypes (6B, 8, 12F, 14, 19A and 23F) compared to baseline.

Persistence of IgG antibody response assessed by Luminex and OPA assays by specific vaccine serotypes.

To assess the effect of temporary MTX discontinuation on disease activity in participants with rheumatoid arthritis, as measured by the Disease Activity Score 28 (DAS28). The DAS28 includes a count of tender and swollen joints (out of 28), a measure of general health (VAS), and either ESR or CRP. Scores range from approximately 0.9 to 9.4, with higher scores indicating worse disease activity.

To evaluate the impact of MTX discontinuation on disease activity in participants with spondyloarthritis, as measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS). The ASDAS combines patient-reported outcomes (back pain, duration of morning stiffness, peripheral pain/swelling, and global assessment) and an objective measure of inflammation (CRP or ESR). Scores range from approximately 0.6 to 6, with higher values indicating worse disease activity.

To assess the frequency of disease flares in participants with systemic lupus erythematosus following MTX discontinuation, using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). SLEDAI-2K scores range from 0 to 105, with higher scores indicating more severe disease activity. A flare is defined as an increase in SLEDAI-2K score from baseline based on pre-established thresholds.

To evaluate the impact of MTX discontinuation on muscle strength in patients with idiopathic inflammatory myopathies, using the Manual Muscle Testing-8 (MMT-8) scale. The MMT-8 score ranges from 0 to 80, with higher scores indicating greater muscle strength and better clinical outcomes. A decrease in score indicates clinical worsening.

To assess the frequency of disease flares following MTX discontinuation in participants with Psoriatic Arthritis, using the Disease Activity Index for Psoriatic Arthritis (DAPSA). Disease flares will be defined as worsening in disease activity classification (e.g., from remission to low, or from low to moderate activity). The DAPSA score ranges as follows: Remission (0-4), Low (5-14), Moderate (15-28) and High (>28). Higher scores indicate worse disease activity.

To evaluate the frequency of disease flares after MTX discontinuation in participants with primary Sjögren's Syndrome using the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). Disease flare will be defined as a clinically significant increase in ESSDAI score. The total ESSDAI score ranges from 0 to 123, with higher scores indicating more severe disease activity.

To determine the frequency of disease flares in patients with Behçet's Disease following MTX discontinuation, using the Behçet's Disease Current Activity Form - Simplified (BDCAF-s). Disease activity will be evaluated based on the presence and severity of clinical features (e.g., oral/genital ulcers, ocular involvement, skin lesions, etc.). Flare will be defined as the appearance or worsening of clinical manifestations as documented in the BDCAF-s.

To evaluate the frequency of disease flares in systemic sclerosis after MTX discontinuation using a composite clinical approach. Flare will be defined as the occurrence of one or more of the following:

Increase in modified Rodnan Skin Score, Development of new digital ulcers, Worsening dyspnea score, Significant clinical change based on the EULAR disease activity assessment for systemic sclerosis.

Safety will be closely monitored, and all serious adverse events will be classified as related or unrelated to the vaccine. A standardized adverse event diary will be provided to all patients and healthy controls for recording local and systemic reactions during the 4 weeks following each vaccine dose. Local reactions include: injection site pain, redness, swelling, bruising, itching, and induration. Systemic reactions include: fever, fatigue, chills, malaise, drowsiness, loss of appetite, nausea, vomiting, diarrhea, abdominal pain, dizziness, tremors, headache, fatigue, myalgia, muscle weakness, arthralgia, pruritus, and skin rash.