Development and Validation of a META-Algorithm to Identify the Indications of Use of Biological Drugs Approved for the Treatment of Immune-Mediated Inflammatory Diseases from Claims Databases: Insights from the VALORE Project

Figures & data

Table 1 Individual IMID-Specific Algorithms Retrieved from the Literature

Databanks	RA	PsO	PsA	UC	CD	SpA	HS	Uveitis
HDR (ICD-9-CM)	714*	696.1	696.0 OR (696.1 AND 721*)	556*	555*	720.0	705.83	36,011 OR 36,012 OR 364* OR 36,320
EXE (exemption from co-payment code / ICD-9CM)	006 OR 006.714* OR 714*	045.696.1 OR 696.1	045.696.0 OR 696.0	009.556 OR 556	009.555 OR 555	054.720.0 OR 720.0 OR 054*
DRUGS (ATC and where necessary specific national drug code)	Auranofin OR Sodium aurothiosulfate^† OR Baricitinib OR Leflunomide^† OR Filgotinib OR Sarilumab	Brodalumab OR Tildrakizumab OR Risankizumab OR (at least two dispensing of Acitretin OR Cyclosporine) OR (Betamethasone AND Salicylic acid) OR (at least two dispensing in one year of Tacalcitol OR Tazarotene) OR (Calcipotriol AND Betamethasone)	PsO algorithm AND (Abatacept OR Anakinra OR Azathioprine OR Certolizumab pegol OR Golimumab OR Hydroxychloroquine OR Leflunomide OR Rituximab OR Sulfasalazine OR Tocilizumab)	Mesalazine^† OR Balsalazide^† OR Budesonide^†	Budesonide^†
OED (Italian coding system)		99.82 (two visits in one year)
COMBINATION OF DATABANKS				EXE: 009 AND Golimumab	EXE: 009 AND Methotrexate^†

Notes: For each single algorithm, each databank or combination of databanks was combined with an OR operator. ^†Specific national drug code.

Abbreviations: ATC, Anatomical therapeutic chemical; EXE, Exemptions from healthcare service co-payment; HDR, Hospital discharge records; HS, Hidradenitis suppurativa; OED, Outpatients encounter data.

Figure 1 Flow chart of incident biological drug users included in the study.

Abbreviations: ETP, Electronic therapeutic plans; ID, Index date; IMID, Immune-mediated inflammatory disease.

Table 2 Validity Estimates of the META-Algorithm According to the Main Analysis

	Acc	Se	Sp	PPV	NPV	Youden Index	F-Score
CD	0.96	0.86	0.97	0.82	0.98	0.84	0.84
UC	0.96	0.80	0.98	0.85	0.97	0.78	0.82
RA	0.93	0.76	0.99	0.95	0.92	0.75	0.84
PsO	0.84	0.89	0.83	0.48	0.98	0.72	0.63
PsA	0.82	0.48	0.95	0.78	0.83	0.43	0.59
SpA	0.97	0.75	0.99	0.85	0.98	0.74	0.79
HS	0.99	0.33	1	1	0.99	0.33	0.50
Uveitis	0.99	0.13	1	1	0.99	0.13	0.23

Abbreviations: Acc, Accuracy; CD, Crohn’s disease; NPV, Negative predictive value; PPV, Positive predictive value; PsO, Psoriasis; PsA, Psoriatic arthritis; RA, Rheumatoid arthritis; Se, Sensitivity; Sp, Specificity; SpA, Spondylarthritis; UC, Ulcerative colitis.

Figure 2 Percentage of indications of use assigned by the META-algorithm against the reference standard.

Abbreviations: CD, Crohn’s disease; PsO, Psoriasis; PsA, Psoriatic arthritis; RA, Rheumatoid arthritis; SpA, Spondyloarthritis; UC, Ulcerative colitis.

Figure 3 Frequency (%) of indication of use stratified by single biological drug across regions (Apulia, Latium, Lombardy, and Veneto).

Note: *Other IMIDs: HS and Uveitis.

Abbreviations: CD, Crohn's disease; UC, Ulcerative colitis; RA, Rheumatoid arthritis; PsO, Psoriasis; PsA, Psoriatic arthritis; SpA, Spondyloarthritis.

Data Sharing Statement

All available data are included in the manuscript and in the Supplementary Materials.