Study on Methotrexate for Plaque-Type Psoriasis

Overview of the Research

A 2016 study investigated the safety and efficacy of a year-long, two-phase regimen of high doses of methotrexate administered via subcutaneous injection for treating plaque-type psoriasis. The findings indicated that this treatment reduces psoriasis severity, enhances quality of life, and is generally well tolerated by patients. Despite being a common first-line treatment for moderate to severe psoriasis, the safety and efficacy of methotrexate under various dosing regimens and administration methods remain inadequately explored.

Details of the Study

Published in The Lancet, the study involved 120 adult participants diagnosed with moderate to severe plaque-type psoriasis at least six months prior to the trial. Notably, these individuals had never received methotrexate before. Participants with psoriatic arthritis, liver dysfunction, or low white blood cell counts were excluded from the study.

The trial consisted of two phases. Phase 1 lasted 16 weeks, during which subjects received weekly injections of either 17.5 mg of 50 mg/mL methotrexate or a placebo. If a 50% reduction in psoriasis severity, measured by the Psoriasis Area Severity Index (PASI), was not achieved by week 8, the dosage was increased to 22.5 mg. Phase 2, lasting 36 weeks, involved all subjects receiving 22.5 mg of methotrexate. If a 75% reduction in PASI score was not seen by week 24, those patients were removed from the study.

All injections were self-administered, except for the initial dose in each phase. To mitigate the risk of low red blood cell counts—a common side effect of methotrexate—patients received 5 mg of oral folic acid 24 hours after each injection. Safety assessments included monitoring for adverse events, conducting physical examinations, measuring vital signs, evaluating quality of life, and assessing drug tolerability. Tissue samples from psoriatic plaques were collected at the beginning of each phase to analyze immune response indicators.

Results of the Trial

Of the original participants, 99 patients (83%) completed Phase 1, and 71 patients (72%) completed Phase 2. At the conclusion of Phase 1, 37 subjects (41%) in the methotrexate group achieved a 75% reduction in PASI scores compared to 3 subjects (10%) in the placebo group. Furthermore, 16 (18%) participants in the methotrexate group experienced a 90% decrease in PASI scores, while no participants in the placebo group reached this threshold.

In Phase 2, a 75% PASI score reduction was observed in 41 (45%) of those who consistently received methotrexate and in 10 (34%) who switched from placebo to methotrexate. Notably, 29 patients (78%) maintained this response from week 16 to week 52, with 28% of all participants experiencing a 90% reduction in psoriasis severity. Additionally, at the 24-week mark, the dose was elevated to 22.5 mg for 5 subjects (23%) who transitioned from placebo to methotrexate and 5 subjects (55%) who remained on methotrexate throughout the study. Among those who continued with methotrexate for the entire trial, 18% achieved a complete 100% reduction in PASI score.

No serious adverse events were reported. Some participants experienced mild adverse effects such as headaches, gastrointestinal issues, or mild infections, common with methotrexate treatment. The quality of life improved significantly, with 59% of patients on methotrexate reporting at least mild disability, compared to 34% in the placebo group, of whom only 10% reported no disability.

Immune Response Indicators

Tissue samples were collected from 27 patients at the beginning of each phase. Among these, 13 patients—6 (23%) on placebo and 7 (26%) on methotrexate—did not experience a significant decrease in PASI scores, while 14 (52%) showed at least a 75% reduction. The study found lower levels of CD11c+ dendritic cells and CD3+ T cells in samples where treatment was effective, indicating that methotrexate may reduce the misidentification of healthy skin cells, thereby diminishing the immune response that leads to skin cell destruction.

Conclusion

The study concluded that the subcutaneous injection of 50 mg/mL methotrexate at a dosage of 17.5 mg for 16 weeks, followed by 22.5 mg for 36 weeks, significantly alleviates the severity of plaque-type psoriasis and improves patient quality of life. This treatment regimen was generally well tolerated. The correlation between immune cell levels and disease severity suggests that methotrexate may effectively combat psoriasis by mitigating immune response errors. Future research involving larger and more diverse populations is necessary to confirm these findings and to compare this regimen with oral methotrexate dosing to determine the optimal route of administration.

Author

Written By: Raishard Haynes, MBS