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. 2022 Jun 2;11(11):3193.
doi: 10.3390/jcm11113193.

Methylprednisolone Plus Low-Dose Methotrexate for Bullous Pemphigoid-A Single Center Retrospective Analysis

Agoritsa Gravani  1 , Georgios Gaitanis  1   2 , Panagiota Spyridonos  3 , Ioannis Alexis  1 , Stelios Tigas  4 , Ioannis D Bassukas  2
Affiliations

Methylprednisolone Plus Low-Dose Methotrexate for Bullous Pemphigoid-A Single Center Retrospective Analysis

Agoritsa Gravani et al. J Clin Med. .

Abstract

Monomodal systemic glucocorticoids remain the mainstay of treatment for bullous pemphigoid (BP). In this retrospective, single-arm study, we evaluated the feasibility (efficacy and tolerability) of the combination of methylprednisolone and low-dose (up to 12.5 mg/week) methotrexate (MP + MTX) for BP. At week 12, 53/55 (96.4%) patients initiated on MP + MTX during a five-year period (potential follow up time: ≥4 years) remained on treatment. At this time-point, BP remission was achieved in all compliant patients (including n = 24 cases of dipeptidyl peptidase-4 inhibitors-associated BP; 12-week remission rate: 100% [95% CI: 91.9-100.0%]; mean time to remission: 29.5 days, SEM: 2.3 days) at a mean cumulative MP dose to disease control of 678.4 mg (SEM = 49.4 mg). Eight patients relapsed during follow up (10.81 [95% CI: 5.16-21.72] relapses/100 person years, py), and seven manifested a severe adverse event (6.80 [95% CI: 3.00-14.28] severe adverse events/100 py); however, 73.4% (±7.9%) had suffered neither a relapse nor a SAE at the three-years follow up. Continuing low dose MP intake (≤8 mg/day) beyond week 12 in combination with MTX minimized the risk of a feasibility limiting event (p = 0.013). Conclusively, the combination of methylprednisolone with methotrexate is a promising, safe, and efficient modality for BP patients, which enables rapid glucocorticoid tapering.

Keywords: bullous pemphigoid; combination treatment; dipeptidyl peptidase-4 inhibitors; glucocorticoid sparing; methotrexate; methylprednisolone.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of the inclusion strategy of the bullous pemphigoid patients. MP: methylprednisolone; MTX: methotrexate; topical: topical glucocorticoids.
Figure 2
Figure 2
Distribution of daily MP doses (A) and weekly MTX doses (B) at treatment start and at the 12-week follow up.
Figure 3
Figure 3
Retention of the treatment. Comparison of the rates of BP patients still receiving MP (solid line) or MTX (dotted line) as a function of time after the onset of the MP plus MTX combination therapy. Short perpendicular bars: censoring events.
Figure 4
Figure 4
“Feasibility-limiting-event”-free survival as a function of the follow up period in months (Kaplan–Meier method). The short perpendicular bars represent censoring events. (A) Relapses, i.e., disease reactivations six months or longer after treatment, started in a patient who had previously achieved disease remission for at least four weeks. (B) Severe adverse events. Inserts: Corresponding comparisons of patients still on low-dose methylprednisolone (4 or 8 mg/day) at week 12 after the start of treatment (grey) vs. already off MP at that time (black). p-values: significance levels of corresponding Log-Rank tests.
Figure 5
Figure 5
Relapse-free survival as a function of follow-up time (in months). Solid line: Gliptin (DPP4i)-related BP. Dashed line: non-gliptin-related BP. The short perpendicular bars represent censoring events. There is no significant difference in the times to relapse between the two patients’ groups (p = 0.257; Log Rank Mantel-Cox test).
See this image and copyright information in PMC

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