Proactive TDM May Improve Adalimumab Response in Psoriasis

Biologic therapies have transformed the treatment landscape for immune-mediated inflammatory diseases (IMIDs), but variability in treatment response remains a persistent challenge. Although tumor necrosis factor (TNF) inhibitors such as adalimumab continue to play a central role in psoriasis management, many patients either fail to achieve an adequate response or lose efficacy over time.¹ New research using pharmacokinetic/pharmacodynamic (PK/PD) modeling suggests that proactive therapeutic drug monitoring (TDM) may improve clinical outcomes for patients receiving adalimumab while also helping identify those more likely to benefit from treatment modification or biologic switching.²

MORE ON PSORIASIS

Investigators analyzed data from 544 patients with psoriasis receiving adalimumab monotherapy through the UK-based BSTOP and PSORT-Discovery cohorts. The study represents the largest PK/PD evaluation of adalimumab conducted across IMIDs to date and drew on real-world data collected from multiple dermatology centers.

The rationale for the study stems from the well-established relationship between biologic drug exposure and clinical response. Previous work has demonstrated that higher serum concentrations of TNF inhibitors are generally associated with improved outcomes up to a therapeutic plateau. In psoriasis, a therapeutic range for adalimumab of 3.2 to 7.0 μg/mL had previously been proposed, but prospective validation through randomized trials remains limited.

To address this evidence gap, researchers developed a population PK/PD model capable of simulating proactive TDM strategies against standard-of-care dosing. The model incorporated serum drug concentrations, antidrug antibody levels, Psoriasis Area and Severity Index (PASI) responses, and patient-specific covariates such as body weight, waist circumference, sex, and comorbidities.

The PK analysis confirmed that adalimumab exhibits linear behavior consistent with prior studies in psoriasis, rheumatoid arthritis, and Crohn disease. Increased drug clearance was associated with higher body weight, larger waist circumference, female sex, hypertension, and the presence of antidrug antibodies. The relationship between antidrug antibodies and clearance further supports the role of immunogenicity in secondary treatment failure.

The PD component used a turnover model to characterize the evolution of psoriasis severity over time. Investigators estimated a lesion turnover half-life of approximately 17 days, aligning with previous biologic studies in psoriasis. However, substantial between-subject variability remained unexplained, underscoring the heterogeneity of biologic response even after accounting for measurable clinical factors.

Using the integrated PK/PD model, investigators simulated a proactive TDM algorithm in which trough drug levels were measured at weeks 5 and 17. Patients with week 5 trough concentrations below 3.2 μg/mL underwent escalation to weekly dosing beginning at week 6. At week 17, treatment decisions were further individualized based on achievement of a 90% reduction in PASI score (PASI90) and serum drug levels.

Compared with standard every-2-week dosing, the proactive TDM strategy improved simulated 6-month PASI90 rates from 28.3% to 38.9%, representing a relative improvement of 37.5%. PASI75 rates increased from 62.4% to 70.4%; these gains came with a 25.9% increase in total adalimumab dose exposure.

The findings also highlighted clinically distinct patient subgroups. Patients with persistently low trough concentrations despite dose escalation were among the least likely to achieve PASI90, suggesting that continued escalation may offer limited benefit in some individuals. According to the investigators, proactive TDM could therefore serve not only as a dosing optimization strategy but also as a tool to identify patients who may be better candidates for switching to alternative biologic classes, including IL-17 or IL-23 inhibitors.

Conversely, a subgroup of patients who achieved PASI90 with trough concentrations above 7 μg/mL underwent simulated dose reduction to every-3-week dosing. Although PASI90 rates in this subgroup declined modestly from 100% to 86.5%, the results suggest that selective de-escalation may be feasible in some well-controlled patients, potentially offsetting treatment costs.

The study arrives as interest in proactive TDM continues to grow across immune-mediated diseases. Reactive TDM is already widely used in inflammatory bowel disease after loss of response, while evidence supporting proactive strategies remains mixed.³ Recent guidelines have cautiously endorsed proactive TDM for maintenance infliximab therapy but have been less supportive of routine proactive monitoring for adalimumab because of limited high-quality evidence.⁴

Although the current analysis was simulation-based rather than prospective, the investigators argue that the results contribute important evidence supporting individualized biologic dosing strategies in psoriasis. The use of real-world registry data was considered a major strength, particularly given the broad representation of UK dermatology practices included through BADBIR.

Several limitations remain. Drug sampling was pragmatic rather than standardized, with both trough and nontrough samples included. Missing dosing information required assumptions regarding adherence and injection timing. In addition, the proactive TDM algorithm was intentionally simplified and evaluated only over a 6-month period.

Still, the study highlights the potential future role of PK/PD-guided precision dosing in dermatology. Investigators noted that Bayesian forecasting models and digital dosing dashboards could eventually support real-time treatment optimization in routine practice. Further prospective studies will be needed to determine whether proactive TDM can consistently improve long-term remission rates, reduce unnecessary drug exposure, and provide a cost-effective alternative to empiric dose escalation or premature biologic switching.

References

1. Kuek A, Hazleman BL, Ostör AJ. Immune-mediated inflammatory diseases (IMIDs) and biologic therapy: a medical revolution. Postgrad Med J. 2007;83(978):251-260. doi:10.1136/pgmj.2006.052688
2. Pan S, Tsakok T, Wei R, et al. Evaluation of a therapeutic drug monitoring strategy for adalimumab in psoriasis: a prospective pharmacokinetic-pharmacodynamic study. Clin Transl Sci. 2026;19(5):e70563. doi:10.1111/cts.70563
3. Wang MY, Zhao JW, Zheng CQ, Sang LX. Therapeutic drug monitoring in inflammatory bowel disease treatments. World J Gastroenterol. 2022;28(15):1604-1607. doi:10.3748/wjg.v28.i15.1604
4. Zeraatkar D, Pitre TS, Kirsh S, et al. Proactive therapeutic drug monitoring of biologic drugs in patients with inflammatory bowel disease, inflammatory arthritis, and psoriasis: systematic review and meta-analysis. BMJ Med. 2024;3(1):e000998. doi:10.1136/bmjmed-2024-000998