Background/Purpose: Due to its efficacy and safety, methotrexate (MTX) has become the first-line disease-modifying drug for rheumatoid (RA) and psoriatic arthritis (PsA). Although  deemed  safe, few studies have analysed  MTX  tolerability. The objective of our study was to ascertain the proportion of RA and PsA patients that discontinue MTX and  the reasons for this.

Methods: A retrospective review of the Rheumatology departments electronic database  was undertaken to identify all patients who had received MTX for RA or PsA. This was followed by review of both the electronic and paper records to identify patients in whom MTX had been discontinued.  The reasons for  this were then classified into several categories. Every effort was made to ensure that the correct reasons for drug withdrawal were documented.  Discrepancies were discussed with a senior member of the team. Cases with insufficient data were excluded from the final analysis.

Results: 1257 patients on MTX were identified. Of these 762 had  RA and 193 had PsA. MTX had been stopped in 260 patients with RA and 71 patients with PsA. In RA patients, the mean dose at the time of discontinuation of MTX was 14.1mg/week (dose range 5 – 30mg, SD 5.6mg) and in PsA patients 13.6mg/week (dose range 5 – 25mg, SD 5.0mg) (missing data in 80 and 26 patients respectively). The reasons for discontinuation and differences between the rheumatoid and psoriatic arthritis groups are highlighted in Table 1 & 2. Our data suggests that about a third of patients with RA and PsA eventually stop methotrexate, most of whom cite intolerance as a reason. In addition  a statistically significant difference between the  RA and PsA cohorts was seen, with abnormalities in blood counts (leucopenia and thrombocytopenia)  being reported more frequently in RA patients (11.5% vs 6.8%; p<0.05) and  more PsA patients having  liver enzyme abnormalities (27% vs 12%; p<0.05).

Table 1: Reasons for methotrexate discontinuation in patients with RA and PsA

Reason for discontinuation	RA (% of all withdrawals)	PsA (% of all withdrawals)	p-value (Χ2-test)
Adverse events	200 (77.5)	44 (62.0)	0.4430
Ineffective	32 (12.4)	13 (18.3)	0.2061
No longer indicated	17 (6.6)	1 (1.4)	–
Patient choice	13(5.0)	10 (14.1)	0.0117
No reason stated	14 (5.4)	6 (8.5)	0.4168

 Table 2: Side-effects leading to methotrexate discontinuation

	RA (% of all withdrawals) n=260	PSA (% of all withdrawals) n=71	p-value (Χ2-test)
All gastrointestinal symptoms    Nausea    Oral ulceration    Diarrhoea    Vomiting    Abdominal pain    Tenesmus	65 (32.5) 41 (20.5) 12 (6.0) 6 (3.0) 4 (2.0) 2 (1.0) 1 (0.5)	12 (27.3) 7 (15.9) 1 (2.3) 3 (6.8) 2 (4.5) 3 (6.8) 0 (0.0)	0.93
All respiratory symptoms    Shortness of breath    Cough    Chest infection	50 (25.0) 19 (9.5) 10 (5.0) 11 (5.5)	6 (13.6) 4 (9.1) 2 (4.5) 0 (0.0)	0.68
Abnormal LFT	24 (12.0)	12 (27.3)	0.029 *
Abnormal FBC    Neutropenia    Thrombocytopenia	23 (11.5) 11 (5.5) 11 (5.5)	3 (6.8) 1 (2.3) 3 (6.8)
Non-specifically unwell	21 (10.5)	5 (11.4)
Neurological and psychological    Headache    Dizzyness	16 (8.0) 6 (3.0) 5 (2.5)	3 (6.8) 1 (2.3) 1 (2.3)
Fatigue	12 (6.0)	3 (6.8)
Cutaneous    Rash    Nodulosis	11 (5.5) 8 (4.0) 3 (1.5)	2 (4.5) 2 (4.5) 0 (0.0)
Renal dysfunction	3 (1.5)	0 (0.0)
Alopecia	2 (1.0)	1 (2.3)
Miscellaneous AEs	7 (3.5)	6 (13.6)
Non-specific intolerance	19 (9.5)	5 (11.4)

Conclusion: Our  data  demonstrates that although MTX is safe, it is not well  tolerated. The differences between MTX tolerability in RA and PsA  is likely to be disease rather than therapy specific. We were  unable to characterise patients who suffer from  side-effects but continue therapy. Thus , the magnitude of the problem is likely to be substantially greater. Poor tolerability is also likely to impact on adherence and in these patients biologic therapy may be indicated.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/how-well-do-patients-with-rheumatoid-and-psoriatic-arthritis-tolerate-methotrexate-a-retrospective-review-of-discontinuation-data-from-a-large-uk-cohort/